U.S. patent application number 17/189162 was filed with the patent office on 2022-01-27 for wearable automatic injection device for controlled administration of therapeutic agents.
The applicant listed for this patent is AbbVie Inc.. Invention is credited to Philip D. Anderson, Sean Corrigan, William Fienup, Joseph F. Julian, Linas P. Laurusonis, Tomas Matusaitis, Chris Strahm.
Application Number | 20220023544 17/189162 |
Document ID | / |
Family ID | |
Filed Date | 2022-01-27 |
United States Patent
Application |
20220023544 |
Kind Code |
A1 |
Anderson; Philip D. ; et
al. |
January 27, 2022 |
WEARABLE AUTOMATIC INJECTION DEVICE FOR CONTROLLED ADMINISTRATION
OF THERAPEUTIC AGENTS
Abstract
Exemplary embodiments provide wearable automatic injection
devices for administering a therapeutic agent to a patient's body
at fast, controlled rates, for example, in a single fast bolus.
Exemplary embodiments also provide methods for assembling wearable
automatic injection devices for administering a therapeutic agent
to a patient at fast, controlled rates. Exemplary embodiments also
provide methods for using wearable automatic injection devices for
administering a therapeutic agent to a patient at fast, controlled
rates.
Inventors: |
Anderson; Philip D.;
(Libertyville, IL) ; Julian; Joseph F.;
(Libertyville, IL) ; Laurusonis; Linas P.;
(Gurnee, IL) ; Corrigan; Sean; (Chicago, IL)
; Fienup; William; (St. Louis, MO) ; Matusaitis;
Tomas; (Chicago, IL) ; Strahm; Chris;
(Deforest, WI) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
AbbVie Inc. |
North Chicago |
IL |
US |
|
|
Appl. No.: |
17/189162 |
Filed: |
March 1, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15966809 |
Apr 30, 2018 |
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17189162 |
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14111933 |
Jan 20, 2014 |
9956345 |
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PCT/US2012/034683 |
Apr 23, 2012 |
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15966809 |
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61478039 |
Apr 21, 2011 |
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International
Class: |
A61M 5/20 20060101
A61M005/20; A61M 5/142 20060101 A61M005/142; A61M 5/00 20060101
A61M005/00; A61M 5/24 20060101 A61M005/24; A61M 5/32 20060101
A61M005/32 |
Claims
1. A wearable automatic injection device for administering a
therapeutic agent to a patient, the wearable automatic injection
device comprising: a housing comprising a patient contact portion
for contacting the patient; an administration assembly moveably
disposed in the housing holding an administration interface for
administering the therapeutic agent to the patient, the
administration assembly moveable between a retracted position in
which the administration interface does not protrude outside the
housing and an extended position in which the administration
interface protrudes outside the housing, the administration
interface includes any of the following needle types, a single
needle, a plurality of needles, a needle coupled to a tubing, a
plurality of needles coupled to a tubing, an array of micro
needles, an array of dissolvable micro needles, a needle-free pad,
or a needle-free patch; a vessel provided in the housing for
holding the therapeutic agent; a plunger actuation mechanism
moveably disposed in the vessel for ejecting the therapeutic agent
from the vessel into the administration assembly; and an
administration interface locking mechanism for automatically
locking the administration interface in the retracted position
within the housing in a pre-administration state and a
post-administration state.
2. The wearable automatic injection device of claim 1, further
comprising: a retraction trigger responsive to a change of state of
the wearable automatic injection device from an administration
state to a post-administration state; and a retraction mechanism
for automatically retracting the administration assembly from the
extended position in the administration state to the retracted
position in the post-administration state upon triggering by the
retraction trigger.
3. The wearable automatic injection device of claim 1, wherein the
vessel comprises a syringe.
4. The wearable automatic injection device of claim 3, wherein the
syringe comprises: a barrel portion for holding the therapeutic
agent; and a piercing needle coupled to a distal end of the barrel
portion for establishing fluid communication between the barrel
portion of the syringe and the administration assembly.
5. The wearable automatic injection device of claim 4, wherein the
administration assembly comprises: a septum that is pierceable by
the piercing needle of the syringe; and a fluid conduit extending
between the administration interface and the septum, wherein
piercing of the septum by the piercing needle of the syringe
couples the barrel portion of the syringe and the administration
interface.
6. The wearable automatic injection device of claim 5, wherein the
piercing needle of the syringe is spaced from the septum when the
device is in a pre- administration state, and wherein the piercing
needle pierces the septum when the device is in an administration
state.
7. The wearable automatic injection device of claim 1, wherein the
vessel comprises a cartridge.
8. The wearable automatic injection device of claim 7, wherein the
cartridge comprises a barrel portion for holding the therapeutic
agent; and a septum that is pierceable by a piercing needle.
9. The wearable automatic injection device of claim 8, wherein the
administration assembly comprises: the piercing needle for
establishing fluid communication between the barrel portion of the
cartridge and the administration interface; and a fluid conduit
provided between the administration interface and the piercing
needle for establishing fluid communication between the
administration interface and the barrel portion of the
cartridge.
10. The wearable automatic injection device of claim 9, wherein
piercing of the septum by the piercing needle of the administration
assembly establishes fluid communication between the barrel portion
of the cartridge and the administration interface.
11. The wearable automatic injection device of claim 10, wherein
the septum of the cartridge is spaced from the piercing needle of
the administration assembly when the device is in a
pre-administration state, and wherein the piercing needle pierces
the septum when the device is in an administration state.
12. The wearable automatic injection device of claim 1, wherein the
vessel is moveably disposed within the housing.
13. The wearable automatic injection device of claim 12, wherein
the vessel is moveable between a first position in a
pre-administration state and a second position in an administration
state.
14. The wearable automatic injection device of claim 13, further
comprising: a vessel actuator for automatically actuating the
vessel from the first position to the second position.
15. The wearable automatic injection device of claim 14, wherein a
fluid pathway is established between the administration assembly
and the vessel, when the administration assembly is in the extended
position and the vessel is in the second position in the
administration state.
16. The wearable automatic injection device of claim 1, wherein the
plunger actuation mechanism administers the therapeutic agent to
the patient at a controlled linear rate.
17. The wearable automatic injection device of claim 1, wherein the
plunger actuation mechanism further comprises: a plunger configured
to exert an expulsion force to the therapeutic agent in the vessel;
a source of a working fluid for providing a hydraulic pressure to
the plunger; and a fluid conduit provided between the source of the
working fluid and the plunger.
18. The wearable automatic injection device of claim 17, wherein
the plunger actuation mechanism further comprises: a damping
mechanism coupled to the plunger and the source of the working
fluid to regulate the ejection of the therapeutic agent from the
vessel.
19. The wearable automatic injection device of claim 18, wherein
the damping mechanism comprises a flow restrictor for maintaining a
first hydraulic pressure downstream of the flow restrictor toward
the vessel at a lower pressure than a second hydraulic pressure
upstream of the flow restrictor toward the source of the working
fluid.
20. The wearable automatic injection device of claim 19, wherein
the flow restrictor is coupled to a retraction trigger, wherein
administration of the therapeutic agent in the vessel causes the
flow restrictor to activate the retraction trigger, and wherein
activation of the retraction trigger automatically retracts the
administration assembly from the extended position to the retracted
position.
21. The wearable automatic injection device of claim 1, wherein the
administration interface locking mechanism comprises: a barrier
mechanism moveably disposed over an administration interface
aperture in the housing; wherein the administration interface
aperture allows the administration interface to protrude outside
the housing when the barrier mechanism is in a first position; and
wherein the administration interface aperture prevents the
administration interface from protruding outside the housing when
the barrier mechanism is in a second position.
22. The wearable automatic injection device of claim 1, wherein the
administration interface locking mechanism comprises: an
administration interface lock release mechanism responsive to
retraction of the administration assembly from the extended
position in the administration state to the retraction position in
the post-administration state; and a pivoting member coupled to the
administration interface and to the administration interface lock
release mechanism; wherein activation of the administration
interface lock release mechanism causes the pivoting member to
pivot the administration interface away from an administration
interface aperture in the housing.
23. The wearable automatic injection device of claim 1, wherein,
after insertion of the therapeutic agent in the vessel, a sterility
barrier is maintained around the therapeutic agent contained in the
vessel and an administration pathway taken by the therapeutic agent
during administration to the patient.
24. The wearable automatic injection device of claim 23, wherein
aseptic assembly of the automatic injection device is not required
for maintaining sterility of the therapeutic agent, one or more
skin penetrating surfaces of the administration interface and the
administration pathway taken by the therapeutic agent during
administration to the patient.
25. The wearable automatic injection device of claim 23, wherein
the sterility barrier is provided by: a sterile barrel portion of
the vessel for holding the therapeutic agent; a sterile piercing
needle for establishing a fluid conduit between the barrel portion
of the vessel and the administration interface; a sterile septum of
the administration assembly that is pierceable by the piercing
needle; a sterile fluid conduit of the administration assembly
extending between the administration interface and the septum,
wherein piercing of the septum by the piercing needle of the vessel
establishes fluid communication between the barrel portion of the
vessel and the administration interface; and the administration
interface which is sterile.
26. The wearable automatic injection device of claim 25, further
comprising: a septum cover for covering and maintaining sterility
of the septum; an administration interface cover for covering and
maintaining sterility of the administration interface and the fluid
conduit coupled to the administration interface; and a piercing
needle cover for covering and maintaining sterility of the piercing
needle and the fluid conduit coupled to the piercing needle.
27. The wearable automatic injection device of claim 26, further
comprising: a protective film attached to at least a portion of the
housing, the protective film coupled to the septum cover, the
administration interface cover and the piercing needle cover such
that removal of the protective film from the housing automatically
removes the septum cover, the administration interface cover and
the piercing needle cover.
28. The wearable automatic injection device of claim 27, wherein
the protective film comprises: an attachment mechanism attached to
a package holding the automatic injection device such that removal
of the device from the package removes the protective film from the
housing of the device, the removal of the protective film removing
the septum cover, the administration interface cover and the
piercing needle cover.
29. The wearable automatic injection device of claim 27, wherein
the protective film comprises: a removal mechanism configured to be
pulled in order to remove the protective film from the housing of
the device, the removal of the protective film removing the septum
cover, the administration interface cover and the piercing needle
cover.
30. The wearable automatic injection device of claim 1, wherein the
wearable automatic injection device is operable without power.
31. A method for administering a therapeutic agent to a patient,
the method comprising: providing a wearable automatic injection
device, comprising: a housing comprising a patient contact portion
for contacting the patient, an administration assembly moveably
disposed in the housing holding an administration interface for
administering the therapeutic agent to the patient, the
administration assembly moveable between a retracted position in
which the administration interface does not protrude outside the
housing and an extended position in which the administration
interface protrudes outside the housing, the administration
interface includes any of the following needle types, a single
needle, a plurality of needles, a needle coupled to a tubing, a
plurality of needles coupled to a tubing, an array of micro
needles, an array of dissolvable micro needles, a needle-free pad,
or a needle-free patch, a vessel provided in the housing for
holding the therapeutic agent, a plunger actuation mechanism
moveably disposed in the vessel for ejecting the therapeutic agent
from the vessel into the administration assembly; securing the
wearable automatic injection device to the body of the patient or
an article of clothing on the patient using the patient contact
portion of the housing; administering a volume of the therapeutic
agent to the body of the patient using the wearable automatic
injection device; and automatically moving the administration
assembly to a retracted position following administration of at
least some of the volume of the therapeutic agent.
32. The method of claim 31, wherein the wearable automatic
injection device further comprises: a retraction trigger responsive
to a change of state of the wearable automatic injection device
from an administration state to a post-administration state; and a
retraction mechanism for automatically retracting the
administration assembly from the extended position in the
administration state to the retracted position in the
post-administration state upon triggering by the retraction
trigger.
33. The method of claim 31, wherein the vessel comprises a
syringe.
34. The method of claim 33, wherein the syringe comprises: a barrel
portion for holding the therapeutic agent; and a piercing needle
coupled to a distal end of the barrel portion for establishing
fluid communication between the barrel portion of the syringe and
the administration assembly.
35. The method of claim 34, wherein the administration assembly
comprises: a septum that is pierceable by the piercing needle of
the syringe; and a fluid conduit extending between the
administration interface and the septum, wherein piercing of the
septum by the piercing needle of the syringe couples the barrel
portion of the syringe and the administration interface.
36. The method of claim 35, wherein the piercing needle of the
syringe is spaced from the septum when the device is in a
pre-administration state, and wherein the piercing needle pierces
the septum when the device is in an administration state.
37. The method of claim 31, wherein the vessel comprises a
cartridge.
38. The method of claim 37, wherein the cartridge comprises: a
barrel portion for holding the therapeutic agent; and a septum that
is pierceable by a piercing needle.
39. The method of claim 38, wherein the administration assembly
comprises: the piercing needle for establishing fluid communication
between the barrel portion of the cartridge and the administration
interface; and a fluid conduit provided between the administration
interface and the piercing needle for establishing fluid
communication between the administration interface and the barrel
portion of the cartridge.
40. The method of claim 39, wherein piercing of the septum by the
piercing needle of the administration assembly establishes fluid
communication between the barrel portion of the cartridge and the
administration interface.
41. The method of claim 40, wherein the septum of the cartridge is
spaced from the piercing needle of the administration assembly when
the device is in a pre-administration state, and wherein the
piercing needle pierces the septum when the device is in an
administration state.
42. The method of claim 31, wherein the plunger actuation mechanism
administers the therapeutic agent to the patient at a controlled
linear rate.
43. The method of claim 31, wherein the plunger actuation mechanism
further comprises: a plunger configured to exert an expulsion force
to the therapeutic agent in the vessel; a source of a working fluid
for providing a hydraulic pressure to the plunger; and a fluid
conduit provided between the source of the working fluid and the
plunger.
44. The method of claim 43, wherein the plunger actuation mechanism
further comprises: a damping mechanism coupled to the plunger and
the source of the working fluid to regulate the ejection of the
therapeutic agent from the vessel.
45. The method of claim 44, wherein the damping mechanism comprises
a flow restrictor for maintaining a first hydraulic pressure
downstream of the flow restrictor toward the vessel at a lower
pressure that a second hydraulic pressure upstream of the flow
restrictor toward the source of the working fluid.
46. The method of claim 45, wherein the flow restrictor is coupled
to a retraction trigger, wherein administration of the therapeutic
agent in the vessel causes the flow restrictor to activate the
retraction trigger, and wherein activation of the retraction
trigger automatically retracts the administration assembly from the
extended position to the retracted position.
47. The method of claim 31, wherein the wearable automatic
injection device further comprises: an administration interface
locking mechanism for automatically locking the administration
interface in the retracted position within the housing in a
post-administration state.
48. The method of claim 47, wherein the administration interface
locking mechanism comprises: a barrier mechanism moveably disposed
over an administration interface aperture in the housing; wherein
the administration interface aperture allows the administration
interface to protrude outside the housing when the barrier
mechanism is in a first position; and wherein the administration
interface aperture prevents the administration interface from
protruding outside the housing when the barrier mechanism is in a
second position.
49. The method of claim 48, wherein the administration interface
locking mechanism comprises: an administration interface lock
release mechanism responsive to retraction of the administration
assembly from the extended position in an administration state to
the retraction position in the post-administration state; and a
pivoting member coupled to the administration interface and to the
administration interface lock release mechanism; wherein activation
of the administration interface lock release mechanism causes the
pivoting member to pivot the administration interface away from an
administration interface aperture in the housing.
50. The method of claim 31, wherein the wearable automatic
injection device is operable without power.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 14/111,933 filed Jan. 20, 2014, which is a 35 U.S.C. .sctn. 371
National Stage Entry of International Application No.
PCT/US2012/034683, filed Apr. 23, 2012. International Application
No. PCT/US2012/034683 is a non-provisional of and claims the
benefit of priority to U.S. Provisional Patent Application Ser. No.
61/478,039, filed Apr. 21, 2011. This application is also related
to U.S. patent application Ser. No. 13/092,102, filed Apr. 21, 2011
(published as U.S. Patent Publication No. 2012-0022499 A1 on Jan.
26, 2012), U.S. patent application Ser. No. 14/872,949, filed Oct.
1, 2015 (published as U.S. Patent Publication No. 2016-0082189 A1
on Mar. 24, 2016), and U.S. patent application Ser. No. 15/818,576,
filed Nov. 20, 2017. The entire contents of each of the
above-referenced applications are expressly incorporated herein by
reference in their entirety.
BACKGROUND
[0002] Automatic injection devices offer an alternative to
manually-operated syringes for administering therapeutic agents
into patients' bodies and allowing patients to self-administer
therapeutic agents. Automatic injection devices have been used to
administer medications under emergency conditions, for example, to
administer epinephrine to counteract the effects of a severe
allergic reaction. Automatic injection devices have also been
described for use in administering anti-arrhythmic medications and
selective thrombolytic agents during a heart attack (See, for
example, U.S. Pat. Nos. 3,910,260; 4,004,577; 4,689,042; 4,755,169;
and 4,795,433). Various types of automatic injection devices are
also described in, for example, U.S. Pat. Nos. 3,941,130;
4,261,358; 5,085,642; 5,092,843; 5,102,393; 5,267,963; 6,149,626;
6,270,479; and 6,371,939; and PCT Publication No. WO/2008/005315,
all of which are incorporated herein in their entirety by
reference.
[0003] Conventionally, an automatic injection device houses a
syringe and, when operated, causes the syringe to move forwardly
and a needle to project from the housing so that a therapeutic
agent contained in the syringe is administered to a patient's body.
Conventional automatic injection devices include hand-held
automatic injection devices and patch pumps, which are
self-adhesive, patient-mounted auto-injectors. In use, a patch pump
containing a therapeutic agent is mounted onto the body or clothing
of a patient and triggered to administer the therapeutic agent to
the patient. Conventional patch pumps are typically filled by a
patient prior to use. In addition, certain conventional patch pumps
have an exposed needle inside the pump, and thus require secondary
sterile packaging to maintain sterility.
SUMMARY
[0004] Exemplary embodiments provide wearable automatic injection
devices that may adhere to the skin or clothing of a patient and
administer a therapeutic agent to the patient at fast, controlled
administration rates, for example, in a single fast bolus.
Exemplary embodiments also provide methods of assembling wearable
automatic injection devices. Exemplary embodiments also provide
methods of using wearable automatic injection devices worn by a
patient for fast, controlled therapeutic agent administration.
Exemplary wearable automatic injection devices reduce or eliminate
a burning sensation often felt or perceived by patients who use a
conventional automatic injection device. Exemplary wearable
automatic injection devices maintain sterility of the therapeutic
agent (for example, a syringe), are easy to use, pre-fill capable,
easy to manufacture, and/or do not require aseptic assembly. The
wearable automatic injection devices provided by exemplary
embodiments be used to administer any therapeutic agent to a
patient including, but not limited to, a biologic drug, such as,
for example, a TNF.alpha. inhibitor, an antibody, insulin, and the
like.
[0005] In accordance with an exemplary embodiment, a wearable
automatic injection device is provided for administering a
therapeutic agent to a patient. The device includes a housing
including a patient contact portion for contacting the skin of the
patient. The device also includes an administration assembly
moveably disposed in the housing and bearing an administration
interface for administering the therapeutic agent to the patient.
The administration assembly is moveable between a retracted
position in which the administration interface does not protrude
outside the housing and an extended position in which the
administration interface protrudes outside the housing. The device
also includes a vessel provided in the housing for holding the
therapeutic agent and a plunger actuation mechanism moveably
disposed in the vessel for ejecting the therapeutic agent from the
vessel into the administration assembly. A volume of the
therapeutic agent of between 0.1 milliliters and 1.0 milliliter is
ejected from the vessel in less than thirty seconds.
[0006] In accordance with another exemplary embodiment, a method is
provided for administering a therapeutic agent to a patient. The
method includes providing a wearable automatic injection device
including a housing including a patient contact portion for
contacting the skin of the patient. The device also includes an
administration assembly moveably disposed in the housing and
bearing an administration interface for administering the
therapeutic agent to the patient. The administration assembly is
moveable between a retracted position in which the administration
interface does not protrude outside the housing and an extended
position in which the administration interface protrudes outside
the housing. The device also includes a vessel provided in the
housing for holding the therapeutic agent and a plunger actuation
mechanism moveably disposed in the vessel for ejecting the
therapeutic agent from the vessel into the administration assembly.
The method includes securing the wearable automatic injection
device to the skin of the patient using the patient contact portion
of the housing. The method also includes administering a volume of
the therapeutic agent of between 0.1 milliliters and 1.0 milliliter
to the patient using the wearable automatic injection device in
less than thirty seconds.
[0007] In accordance with another exemplary embodiment, a method is
provided for assembling a wearable automatic injection device. The
method includes assembling a first portion of the automatic
injection device in a sterile environment to hold a sterile dose of
a therapeutic agent. The method includes providing one or more
sterility barrier components associated with the first portion of
the device to maintain sterility, during and after assembly of the
automatic injection device, of a fluid pathway taken by the
therapeutic agent during administration to a patient. The method
also includes assembling a second portion of the automatic
injection device in a non-sterile environment while maintaining
sterility of the first portion of the automatic injection
device.
[0008] In accordance with another exemplary embodiment, a wearable
automatic injection device is provided for administering a
therapeutic agent to a patient. The device includes a housing
including a patient contact portion for contacting the skin of the
patient. The device also includes an administration assembly
moveably disposed in the housing and bearing an administration
interface for administering the therapeutic agent to the patient,
the administration assembly moveable between a retracted position
in which the administration interface does not protrude outside the
housing and an extended position in which the administration
interface protrudes outside the housing. The device also includes a
vessel provided in the housing for holding the therapeutic agent
and a plunger actuation mechanism moveably disposed in the vessel
for ejecting the therapeutic agent from the vessel into the
administration assembly. The device also includes a retraction
trigger responsive to a change of state of the wearable automatic
injection device from an administration state to a
post-administration state, and a retraction mechanism for
automatically retracting the administration assembly from the
extended position in the administration state to the retracted
position in the post-administration state upon triggering by the
retraction trigger. A volume of the therapeutic agent of between
0.1 milliliters and 1.0 milliliter is ejected from the vessel in
less than thirty seconds.
[0009] In accordance with another exemplary embodiment, a method is
provided for administering a therapeutic agent to a patient. The
method includes providing a wearable automatic injection device
including a housing including a patient contact portion for
contacting the skin of the patient. The device also includes an
administration assembly moveably disposed in the housing and
bearing an administration interface for administering the
therapeutic agent to the patient, the administration assembly
moveable between a retracted position in which the administration
interface does not protrude outside the housing and an extended
position in which the administration interface protrudes outside
the housing. The device also includes a vessel provided in the
housing for holding the therapeutic agent and a plunger actuation
mechanism moveably disposed in the vessel for ejecting the
therapeutic agent from the vessel into the administration assembly.
The device also includes a retraction trigger responsive to a
change of state of the wearable automatic injection device from an
administration state to a post-administration state, and a
retraction mechanism for automatically retracting the
administration assembly from the extended position in the
administration state to the retracted position in the
post-administration state upon triggering by the retraction
trigger. The method includes securing the wearable automatic
injection device to the skin of the patient using the patient
contact portion of the housing. The method also includes
administering a volume of the therapeutic agent of between 0.1
milliliters and 1.0 milliliter to the patient using the wearable
automatic injection device in less than thirty seconds.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The foregoing and other objects, aspects, features, and
advantages of exemplary embodiments will become more apparent and
may be better understood by referring to the following description
taken in conjunction with the accompanying drawings, in which:
[0011] FIG. 1A illustrates a first end view and a first side view
of an exemplary wearable device including a cartridge assembly in a
packaged pre-administration state.
[0012] FIG. 1B illustrates the first end view and the first side
view of the exemplary device of FIG. 1A in a pre-administration
state before administration of a therapeutic agent in which a cover
covering the administration interface is removed in preparation for
an administration of the therapeutic agent.
[0013] FIG. 1C illustrates the first end view and the first side
view of the exemplary device of FIG. 1A in an administration state
during administration of a therapeutic agent in which the
administration interface interfaces with the patient's body.
[0014] FIG. 1D illustrates the first end view and the first side
view of the exemplary device of FIG. 1A in an administration state
during administration of a therapeutic agent in which a barrel
portion of the device containing a dose of the therapeutic agent is
deployed forwardly within the housing of the device.
[0015] FIG. 1E illustrates the first end view and the first side
view of the exemplary device of FIG. 1A in an administration state
during administration of a therapeutic agent in which a bung of the
device is actuated by a plunger actuator to expel the dose of the
therapeutic agent from the barrel portion.
[0016] FIG. 1F illustrates the first end view and the first side
view of the exemplary device of FIG. 1A in a post-administration
state after administration of a therapeutic agent in which the
administration interface is retracted within the housing of the
device.
[0017] FIG. 2A illustrates a first end view and a first side view
of an exemplary wearable device including a syringe assembly in a
packaged pre-administration state.
[0018] FIG. 2B illustrates the first end view and the first side
view of the exemplary device of FIG. 2A in a pre-administration
state before administration of a therapeutic agent in which a cover
covering the administration interface is removed in preparation for
administration of the therapeutic agent.
[0019] FIG. 2C illustrates the first end view and the first side
view of the exemplary device of FIG. 2A in an administration state
during administration of a therapeutic agent in which the
administration interface interfaces with the patient's body.
[0020] FIG. 2D illustrates the first end view and the first side
view of the exemplary device of FIG. 2A in an administration state
during administration of a therapeutic agent in which a barrel
portion of the device containing a dose of the therapeutic agent is
deployed forwardly within the housing of the device.
[0021] FIG. 2E illustrates the first end view and the first side
view of the exemplary device of FIG. 2A in an administration state
during administration of a therapeutic agent in which a bung of the
device is actuated by a plunger actuator to expel the dose of the
therapeutic agent from the barrel portion.
[0022] FIG. 2F illustrates the first end view and the first side
view of the exemplary device of FIG. 2A in a post-administration
state after administration of a therapeutic agent in which the
administration interface is retracted within the housing of the
device.
[0023] FIG. 3 is a flow chart of an exemplary method of assembling
an exemplary wearable automatic injection device.
[0024] FIG. 4 is a flow chart of an exemplary method of using an
exemplary automatic wearable injection device.
[0025] FIG. 5 is a flow chart of an exemplary method of using an
exemplary wearable automatic injection device to administer a
therapeutic agent to a patient.
[0026] FIG. 6A illustrates an exemplary wearable automatic
injection device suitable for linear insertion into or application
to a patient's body in a pre-administration state.
[0027] FIG. 6B illustrates the exemplary device of FIG. 6A in an
administration state ready to administer or in the process of
administering a dose of a therapeutic agent to a patient.
[0028] FIG. 6C illustrates the exemplary device of FIGS. 6A and 6B
in a post-administration state after it has completed administering
the therapeutic agent to the patient or removed from the patient
prior to completion of the administration of the therapeutic
agent.
[0029] FIG. 7A illustrates an exemplary wearable automatic
injection device suitable for rotary insertion in a
pre-administration state ready for use by a patient.
[0030] FIG. 7B illustrates the exemplary device of FIG. 7A in an
administration state ready to administer or in the process of
administering a dose of a therapeutic agent to a patient.
[0031] FIG. 7C illustrates the exemplary device of FIGS. 7A and 7B
in a post-administration state after it has completed administering
the therapeutic agent to the patient or removed from the patient
prior to completion of the administration of the therapeutic
agent.
[0032] FIG. 8 is a flow chart of an exemplary method of assembling
an exemplary wearable automatic injection device.
[0033] FIG. 9 is a flow chart of an exemplary method of using an
exemplary wearable automatic injection device.
[0034] FIG. 10 is a flow chart of an exemplary method of using an
exemplary wearable automatic injection device to administer a
therapeutic agent to a patient.
[0035] FIG. 11A illustrates a perspective view of an exemplary
wearable automatic injection device.
[0036] FIG. 11B illustrates an exploded view showing the components
of the device of FIG. 11A.
[0037] FIG. 12A illustrates a side view of an exemplary wearable
automatic injection device.
[0038] FIG. 12B illustrates a perspective view showing the
components of the device of FIG. 12A.
[0039] FIG. 13A illustrates a perspective view of an exemplary
wearable automatic injection device.
[0040] FIG. 13B illustrates a top view of the device of FIG.
13A.
[0041] FIG. 13C illustrates a sectional side view of the transfer
mechanism of the device of FIG. 13A.
[0042] FIG. 14A illustrates a perspective view of an exemplary
wearable automatic injection device including an exemplary
cartridge assembly.
[0043] FIG. 14B illustrates a sectional side view of the exemplary
cartridge assembly of FIG. 14A taken along the longitudinal
axis.
[0044] FIG. 14C illustrates a transparent top view of the device of
FIG. 14A.
[0045] FIG. 15 illustrates an exemplary barrel portion in which a
distal end of the barrel portion bears an administration interface
that extends substantially along the longitudinal axis of the
barrel portion.
[0046] FIG. 16 illustrates an exemplary barrel portion in which a
distal end of the barrel portion bears an administration interface
that extends at about 90 degrees relative to the longitudinal axis
of the barrel portion.
[0047] FIG. 17 illustrates an exemplary assembly in which an
exemplary adapter couples a piercing needle to an administration
interface.
[0048] FIG. 18 illustrates an exemplary assembly in which a fluid
conduit couples a piercing needle to an administration
interface.
[0049] FIG. 19 illustrates an exemplary transfer mechanism for
providing a fluid conduit between a piercing needle and an
administration interface.
[0050] FIG. 20 illustrates an exemplary transfer mechanism for
providing a fluid conduit between a piercing needle and an
administration interface.
[0051] FIG. 21 illustrates an exemplary transfer mechanism for
providing a fluid conduit between a piercing needle and an
administration interface.
[0052] FIG. 22 illustrates an exemplary syringe or cartridge
actuator that may be used to advance a syringe or cartridge
assembly from a retraction position to an extended position within
the housing of a wearable automatic injection device.
[0053] FIG. 23 illustrates an exemplary syringe or cartridge
actuator including a first portion, a second portion and a hinge
portion provided between the first and second portions.
[0054] FIG. 24 is a perspective view through a cover of an
exemplary automatic injection device including a plunger actuation
mechanism that employs one or more fluid circuits.
[0055] FIG. 25 illustrates a graph of the cumulative volume of
therapeutic agent (in milliliters) against time (in seconds) as
administered by an exemplary administration system including a flow
restrictor.
[0056] FIG. 26 is a schematic drawing of an exemplary automatic
injection device including a plunger actuation mechanism that
employs one or more fluid circuits.
[0057] FIG. 27 is a top view of the exemplary device of FIG.
26.
[0058] FIG. 28 illustrates a top view of an exemplary automatic
injection device which shows a conduit coupling a master cylinder
of a working fluid to a flow restrictor, a conduit coupling the
flow restrictor to a bung, and a conduit coupling the master
cylinder to a retraction mechanism via a valve.
[0059] FIG. 29 illustrates a schematic diagram of the device of
FIG. 28.
[0060] FIG. 30 illustrates a graph of exemplary pressures after a
check valve and behind a bung (in psi) versus time (in seconds) in
an exemplary automatic injection device.
[0061] FIG. 31 illustrates a side view of an exemplary automatic
injection device in which the housing of the wearable automatic
injection device includes a skin sensor foot.
[0062] FIGS. 32A and 32B illustrate an exemplary administration
interface protection system that maintains an administration
interface in a retracted position within the housing of an
exemplary automatic injection device.
[0063] FIGS. 33A and 33B illustrate another exemplary
administration interface protection system that maintains an
administration interface in a retracted position within the housing
of an exemplary automatic injection device.
[0064] FIG. 34 illustrates another exemplary administration
interface protection system that maintains an administration
interface in a retracted position within the housing of an
exemplary automatic injection device.
[0065] FIG. 35A illustrates a perspective view of another exemplary
administration interface protection system that maintains an
administration interface in a retracted position within the housing
of an exemplary automatic injection device.
[0066] FIG. 35B illustrates a top view of the exemplary
administration interface protection system of FIG. 35A.
[0067] FIG. 35C illustrates a first side view of the exemplary
administration interface protection system of FIG. 35A.
[0068] FIG. 35D illustrates a second side view of the exemplary
administration interface protection system of FIG. 35A in which the
automatic injection device is in an administration state.
[0069] FIG. 35E illustrates the second side view of the exemplary
administration interface protection system of FIG. 35A in which the
automatic injection device is in a pre- or post-administration
state.
[0070] FIG. 36 illustrates a first end view and a first side view
of the exemplary wearable device of FIG. 1A in a pre-administration
state within an outer packaging in which a removal mechanism of a
protective film is coupled to a portion of the outer packaging.
[0071] FIG. 37 illustrates a first end view and a first side view
of the exemplary wearable device of FIG. 2A in a pre-administration
state within an outer packaging in which a removal mechanism of a
protective film is coupled to a portion of the outer packaging.
DETAILED DESCRIPTION
[0072] Automatic injection devices offer an alternative to
conventional manually-operated syringes for administering a
therapeutic agent and allow patients to self-administer therapeutic
agents. Exemplary embodiments provide wearable automatic injection
devices that may adhere to the body or clothing of a patient's body
and administer a therapeutic agent to the patient at fast,
controlled administration rates, for example, in a single fast
bolus. Exemplary embodiments also provide methods of using the
wearable automatic injection devices for fast, controlled
therapeutic agent administration.
[0073] In an exemplary embodiment, a volume of about 0.1
milliliters to about 1 milliliter or more of a therapeutic agent
may be administered in an administration time period of about one
second to about twelve hours. In an exemplary embodiment, the
administration time period for the same range of volumes may range
from about one second to about thirty seconds, but is not limited
to this exemplary range. In certain exemplary embodiments,
therapeutic agent volumes of about 0.1 milliliters to about 1
milliliter may be administered in a time duration ranging from
about 3 seconds to about 5 seconds. In certain exemplary
embodiments, therapeutic agent volumes of about 0.1 milliliters to
about 1 milliliter may be administered in time durations of or
shorter than about 20 seconds.
[0074] Exemplary wearable automatic injection devices are
disposable, easy to use, pre-fill capable, and may substantially or
completely eliminate the burning sensation often experienced by a
patient that uses a wearable automatic injection device. The fast,
controlled administration rates achieved by exemplary devices may
minimize the pain sensation associated with a volume of a
therapeutic agent entering into the patent's tissue. Exemplary time
durations for fast administration achieved by exemplary devices may
range from about one second to about thirty seconds, but are not
limited to this exemplary range. Exemplary volumes of therapeutic
agent that may be administered by exemplary devices within the
above time range may range from about 0.1 milliliters to about 1
milliliter, but are not limited to this exemplary range. In certain
exemplary embodiments, therapeutic agent volumes of about 0.1
milliliters to about 1 milliliter may be administered in a time
duration ranging from about 3 seconds to about 5 seconds. In
certain exemplary embodiments, therapeutic agent volumes of about
0.1 milliliters to about 1 milliliter may be administered in a time
duration of or shorter than about 20 seconds. In addition,
exemplary devices may advantageously provide a linear
administration profile, i.e., at a substantially constant rate of
administration, and may minimize inflections and abrupt changes in
the administration profile against time of the therapeutic
agent.
[0075] Exemplary embodiments minimize the size envelope of
exemplary automatic injection devices and provide scalable
solutions with configurable administration times and administration
profiles that may be used for a range of therapeutic agent
viscosities.
[0076] Exemplary embodiments may administer a therapeutic agent to
a patient without requiring battery power or other components
requiring electrical current or charge to operate.
[0077] The wearable automatic injection devices provided by
exemplary embodiments are pre-fillable and/or pre-filled prior to
administration to the patient, maintain sterility of the
therapeutic agent, sterility of all therapeutic agent contact
surfaces and patient contact surfaces (i.e., a vessel containing
the therapeutic agent, one or more fluid conduits in the device,
one or more skin penetrating surfaces of an administration
interface, one or more septa provided in the fluid conduits, and
the like) and sterility of the administration pathway taken by the
therapeutic agent during administration to the patient, in order to
avoid the need for aseptic assembly, and address the perceived
patient discomfort due to injection by conventional hand held
automatic injection devices. Exemplary wearable automatic injection
devices include a primary therapeutic barrel portion that maintains
sterility and therefore requires no aseptic assembly.
[0078] Exemplary automatic injection devices may be used to
administer therapeutic agents in any suitable delivery injection
depth by, for example, subcutaneous injection, intradermal
injection, intramuscular injection, topical administration, and the
like. The wearable automatic injection devices provided by
exemplary embodiments may be used to administer any therapeutic
agent including, but not limited to, an antibody, small molecule,
insulin, and the like. A syringe assembly of exemplary automatic
injection devices may contain a dose of a TNF.alpha. inhibitor. In
an exemplary embodiment, the TNF.alpha. inhibitor may be a human
TNF.alpha. antibody or antigen-biding portion thereof. In an
exemplary embodiment, the human TNF.alpha. antibody or
antigen-binding portion thereof may be adalimumab or golimumab.
[0079] Exemplary embodiments are described below with reference to
certain illustrative embodiments. While exemplary embodiments are
described with respect to using a wearable automatic injection
device to administer a dose of a liquid medication, one of ordinary
skill in the art will recognize that exemplary embodiments are not
limited to the illustrative embodiments and that exemplary
automatic injection devices may be used to administer any suitable
substance to a patient. In addition, components of exemplary
automatic injection devices and methods of making and using
exemplary automatic injection devices are not limited to the
illustrative embodiments described below.
I. Definitions
[0080] Certain terms are defined in this section to facilitate
understanding of exemplary embodiments.
[0081] The wearable automatic injection device of exemplary
embodiments may include a "therapeutically effective amount" or a
"prophylactically effective amount" of an antibody or antibody
portion of the invention. A "therapeutically effective amount"
refers to an amount effective, at dosages and for periods of time
necessary, to achieve the desired therapeutic result. A
therapeutically effective amount of the antibody, antibody portion,
or other TNF.alpha. inhibitor may vary according to factors such as
the disease state, age, sex, and weight of the patient, and the
ability of the antibody, antibody portion, or other TNF.alpha.
inhibitor to elicit a desired response in the patient. A
therapeutically effective amount is also one in which any toxic or
detrimental effects of the antibody, antibody portion, or other
TNF.alpha. inhibitor are outweighed by the therapeutically
beneficial effects. A "prophylactically effective amount" refers to
an amount effective, at dosages and for periods of time necessary,
to achieve the desired prophylactic result. Typically, since a
prophylactic dose is used in patients prior to or at an earlier
stage of disease, the prophylactically effective amount will be
less than the therapeutically effective amount.
[0082] The terms "substance" and "therapeutic agent" refer to any
type of drug, biologically active agent, biological substance,
chemical substance or biochemical substance that is capable of
being administered in a therapeutically effective amount to a
patient employing exemplary automatic injection devices. Exemplary
substances include, but are not limited to, agents in a liquid
state. Such agents may include, but are not limited to, small
molecule therapeutic agents. The therapeutic agent(s) may be used
for treating one or more diseases or physical conditions, e.g.,
pain, cancer, Parkinson's disease, and the like. Such agents may
also include, but are not limited to, adalimumab (HUMIRA.RTM.) and
proteins that are in a liquid solution, for example, fusion
proteins and enzymes. Examples of proteins in solution include, but
are not limited to, Pulmozyme (Dornase alfa), Regranex
(Becaplermin), Activase (Alteplase), Aldurazyme (Laronidase),
Amevive (Alefacept), Aranesp (Darbepoetin alfa), Becaplermin
Concentrate, Betaseron (Interferon beta-1b), BOTOX (Botulinum Toxin
Type A), Elitek (Rasburicase), Elspar (Asparaginase), Epogen
(Epoetin alfa), Enbrel (Etanercept), Fabrazyme (Agalsidase beta),
Infergen (Interferon alfacon-1), Intron A (Interferon alfa-2a),
Kineret (Anakinra), MYOBLOC (Botulinum Toxin Type B), Neulasta
(Pegfilgrastim), Neumega (Oprelvekin), Neupogen (Filgrastim), Ontak
(Denileukin diftitox), PEGASYS (Peginterferon alfa-2a), Proleukin
(Aldesleukin), Pulmozyme (Dornase alfa), Rebif (Interferon
beta-1a), Regranex (Becaplermin), Retavase (Reteplase), Roferon-A
(Interferon alfa-2), TNKase (Tenecteplase), and Xigris (Drotrecogin
alfa), Arcalyst (Rilonacept), NPlate (Romiplostim), Mircera
(methoxypolyethylene glycol-epoetin beta), Cinryze (C1 esterase
inhibitor), Elaprase (idursulfase), Myozyme (alglucosidase alfa),
Orencia (abatacept), Naglazyme (galsulfase), Kepivance (palifermin)
and Actimmune (interferon gamma-1b).
[0083] A protein in solution may also be an immunoglobulin or
antigen-binding fragment thereof, such as an antibody or
antigen-binding portion thereof. Examples of antibodies that may be
used in an exemplary automatic injection device include, but are
not limited to, chimeric antibodies, non-human antibodies, human
antibodies, humanized antibodies, and domain antibodies (dAbs). In
an exemplary embodiment, the immunoglobulin or antigen-binding
fragment thereof, is an anti-TNF.alpha. and/or an anti-IL-12
antibody (for example, it may be a dual variable domain
immunoglobulin (DVD) IgTM). Other examples of immunoglobulins or
antigen-binding fragments thereof that may be used in the methods
and compositions of exemplary embodiments include, but are not
limited to, 1D4.7 (anti-IL-12/IL-23 antibody; Abbott Laboratories);
2.5(E)mg1 (anti-IL-18; Abbott Laboratories); 13C5.5 (anti-IL-13
antibody; Abbott Laboratories); J695 (anti-IL-12; Abbott
Laboratories); Afelimomab (Fab 2 anti-TNF; Abbott Laboratories);
HUMIRA.RTM. (adalimumab) Abbott Laboratories); Campath
(Alemtuzumab); CEA-Scan Arcitumomab (fab fragment); Erbitux
(Cetuximab); Herceptin (Trastuzumab); Myoscint (Imciromab
Pentetate); ProstaScint (Capromab Pendetide); Remicade
(Infliximab); ReoPro (Abciximab); Rituxan (Rituximab); Simulect
(Basiliximab); Synagis (Palivizumab); Verluma (Nofetumomab); Xolair
(Omalizumab); Zenapax (Daclizumab); Zevalin (Ibritumomab Tiuxetan);
Orthoclone OKT3 (Muromonab-CD3); Panorex (Edrecolomab); Mylotarg
(Gemtuzumab ozogamicin); golimumab (Centocor); Cimzia (Certolizumab
pegol); Soliris (Eculizumab); CNTO 1275 (ustekinumab); Vectibix
(panitumumab); Bexxar (tositumomab and 1131 tositumomab); and
Avastin (bevacizumab).
[0084] Additional examples of immunoglobulins, or antigen-binding
fragments thereof, that may be used in the methods and compositions
of exemplary embodiments include, but are not limited to, proteins
comprising one or more of the following: the D2E7 light chain
variable region (SEQ ID NO: 1), the D2E7 heavy chain variable
region (SEQ ID NO: 2), the D2E7 light chain variable region CDR3
(SEQ ID NO: 3), the D2E7 heavy chain variable region CDR3 (SEQ ID
NO:4), the D2E7 light chain variable region CDR2 (SEQ ID NO: 5),
the D2E7 heavy chain variable region CDR2 (SEQ ID NO: 6), the D2E7
light chain variable reion CDR1 (SEQ ID NO: 7), the D2E7 heavy
chain variable region CDR1 (SEQ ID NO: 8), the 2SD4 light chain
variable region (SEQ ID NO: 9), the 2SD4 heavy chain variable
region (SEQ ID NO: 10), the 2SD4 light chain variable CDR3 (SEQ ID
NO: 11), the EP B12 light chain variable CDR3 (SEQ ID NO: 12), the
VL10E4 light chain variable CDR3 (SEQ ID NO: 13), theVL100A9 light
chain variable CDR3 (SEQ ID NO: 14), the VLL100D2 light chain
variable CDR3 (SEQ ID NO: 15), the VLLOF4 light chain variable CDR3
(SEQ ID NO: 16), the LOES light chain variable CDR3 (SEQ ID NO:
17), the VLLOG7 light chain variable CDR3 (SEQ ID NO: 18), the
VLLOG9 light chain variable CDR3 (SEQ ID NO: 19), the VLLOH1 light
chain variable CDR3 (SEQ ID NO: 20), the VLLOH10 light chain
variable CDR3 (SEQ ID NO: 21), the VL1B7 light chain variable CDR3
(SEQ ID NO: 22), the VL1C1 light chain variable CDR3 (SEQ ID NO:
23), the VL0.1F4 light chain variable CDR3 (SEQ ID NO: 24), the
VL0.1H8 light chain variable CDR3 (SEQ ID NO: 25), the LOE7.A light
chain variable CDR3 (SEQ ID NO: 26), the 2SD4 heavy chain variable
region CDR (SEQ ID NO: 27), theVH1B11 heavy chain variable region
CDR (SEQ ID NO: 28), the VH1D8 heavy chain variable region CDR (SEQ
ID NO: 29), the VH1A11 heavy chain variable region CDR (SEQ ID NO:
30), the VH1B12 heavy chain variable region CDR (SEQ ID NO: 31),
the VH1E4 heavy chain variable region CDR (SEQ ID NO: 32), the
VH1F6 heavy chain variable region CDR (SEQ ID NO: 33), the 3C-H2
heavy chain variable region CDR (SEQ ID NO: 34), and the VH1-D2.N
heavy chain variable region CDR (SEQ ID NO: 35).
[0085] The term "human TNF.alpha." (abbreviated herein as
hTNF.alpha., or simply hTNF) refers to a human cytokine that exists
as a 17 kD secreted form and a 26 kD membrane associated form, the
biologically active form of which is composed of a trimer of
noncovalently bound 17 kD molecules. The structure of hTNF.alpha.
is described further in, for example, Pennica, D., et al. (1984)
Nature 312:724-729; Davis, J. M., et al. (1987)
Biochem.26:1322-1326; and Jones, E. Y., et al. (1989) Nature
338:225-228. The term human TNF.alpha. is intended to include
recombinant human TNF.alpha. (rhTNFa), which can be prepared by
standard recombinant expression methods or purchased commercially
(R & D Systems, Catalog No. 210-TA, Minneapolis, Minn.).
TNF.alpha. is also referred to as TNF.
[0086] The term "TNF.alpha. inhibitor" refers to an agent that
interferes with TNF.alpha. activity. The term also includes each of
the anti-TNF.alpha. human antibodies (used interchangeably herein
with TNF.alpha. antibodies) and antibody portions described herein
as well as those described in U.S. Pat. Nos. 6,090,382; 6,258,562;
6,509,015; 7,223,394; and 6,509,015. In one embodiment, the
TNF.alpha. inhibitor used in the invention is an anti-TNF.alpha.
antibody, or a fragment thereof, including infliximab
(Remicade.RTM., Johnson and Johnson; described in U.S. Pat. No.
5,656,272); CDP571 (a humanized monoclonal anti-TNF-alpha IgG4
antibody); CDP 870 (a humanized monoclonal anti-TNF-alpha antibody
fragment); an anti-TNF dAb (Peptech); CNTO 148 (golimumab;
Centocor, See WO 02/12502 and U.S. Pat. No. 7,521,206 and U.S. Pat.
No. 7,250,165); and adalimumab (HUMIRA.RTM. Abbott Laboratories, a
human anti-TNF mAb, described in U.S. Pat. No. 6,090,382 as D2E7).
Additional TNF antibodies that may be used in the invention are
described in U.S. Pat. Nos. 6,593,458; 6,498,237; 6,451,983; and
6,448,380. In another embodiment, the TNF.alpha. inhibitor is a TNF
fusion protein, for example, etanercept (Enbrel.RTM., Amgen;
described in WO 91/03553 and WO 09/406476). In another embodiment,
the TNF.alpha. inhibitor is a recombinant TNF binding protein
(r-TBP-I) (Serono).
[0087] In one embodiment, the term "TNF.alpha. inhibitor" excludes
infliximab. In one embodiment, the term "TNF.alpha. inhibitor"
excludes adalimumab. In another embodiment, the term "TNF.alpha.
inhibitor" excludes adalimumab and infliximab.
[0088] In one embodiment, the term "TNF.alpha. inhibitor" excludes
etanercept, and, optionally, adalimumab, infliximab, and adalimumab
and infliximab.
[0089] In one embodiment, the term "TNF.alpha. antibody" excludes
infliximab. In one embodiment, the term "TNF.alpha. antibody"
excludes adalimumab. In another embodiment, the term "TNF.alpha.
antibody" excludes adalimumab and infliximab.
[0090] The term "antibody" refers to immunoglobulin molecules
generally comprised of four polypeptide chains, two heavy (H)
chains and two light (L) chains inter-connected by disulfide bonds.
Each heavy chain is comprised of a heavy chain variable region
(abbreviated herein as HCVR or VH) and a heavy chain constant
region. The heavy chain constant region is comprised of three
domains, CH1, CH2 and CH3. Each light chain is comprised of a light
chain variable region (abbreviated herein as LCVR or VL) and a
light chain constant region. The light chain constant region is
comprised of one domain, CL. The VH and VL regions can be further
subdivided into regions of hypervariability, termed complementarity
determining regions (CDR), interspersed with regions that are more
conserved, termed framework regions (FR). Each VH and VL is
composed of three CDRs and four FRs, arranged from amino-terminus
to carboxy-terminus in the following order: FR1, CDR1, 1-R2, CDR2,
FR3, CDR3, FR4. The antibodies of the invention are described in
further detail in U.S. Pat. Nos. 6,090,382; 6,258,562; and
6,509,015.
[0091] The term "antigen-binding portion" of an antibody (or simply
"antibody portion") refers to one or more fragments of an antibody
that retain the ability to specifically bind to an antigen (for
example, hTNFa). Fragments of a full-length antibody can perform
the antigen-binding function of an antibody. Examples of binding
fragments encompassed within the term "antigen-binding portion" of
an antibody include (i) a Fab fragment, a monovalent fragment
consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab')2
fragment, a bivalent fragment comprising two Fab fragments linked
by a disulfide bridge at the hinge region; (iii) a Fd fragment
consisting of the VH and CH1 domains; (iv) a Fv fragment consisting
of the VL and VH domains of a single arm of an antibody, (v) a dAb
fragment (Ward et al. (1989) Nature 341:544-546), which consists of
a VH or VL domain; (vi) an isolated complementarity determining
region (CDR); and (vii) a dual variable domain immunoglobulin
(DVD-Ig). Furthermore, although the two domains of the Fv fragment,
VL and VH, are coded for by separate genes, they can be joined,
using recombinant methods, by a synthetic linker that enables them
to be made as a single protein chain in which the VL and VH regions
pair to form monovalent molecules (known as single chain Fv (scFv);
See, for example, Bird et al. (1988) Science 242:423-426; and
Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). Such
single chain antibodies are also encompassed within the term
"antigen-binding portion" of an antibody. Other forms of single
chain antibodies, such as diabodies are also encompassed. Diabodies
are bivalent, bispecific antibodies in which VH and VL domains are
expressed on a single polypeptide chain, but using a linker that is
too short to allow for pairing between the two domains on the same
chain, thereby forcing the domains to pair with complementary
domains of another chain and creating two antigen binding sites
(See, for example, Holliger et al. (1993) Proc. Natl. Acad. Sci.
USA 90:6444-6448; Poljak et al. (1994) Structure 2:1121-1123). The
antibody portions of the invention are described in further detail
in U.S. Pat. Nos. 6,090,382; 6,258,562; and 6,509,015.
[0092] The term "recombinant human antibody" refers to all human
antibodies that are prepared, expressed, created or isolated by
recombinant means, such as antibodies expressed using a recombinant
expression vector transfected into a host cell (described further
below), antibodies isolated from a recombinant, combinatorial human
antibody library (described further below), antibodies isolated
from an animal (for example, a mouse) that is transgenic for human
immunoglobulin genes (See, for example, Taylor et al. (1992) Nucl.
Acids Res. 20:6287) or antibodies prepared, expressed, created or
isolated by any other means that involves splicing of human
immunoglobulin gene sequences to other DNA sequences. Such
recombinant human antibodies have variable and constant regions
derived from human germ line immunoglobulin sequences. In certain
embodiments, however, such recombinant human antibodies are
subjected to in vitro mutagenesis (or, when an animal transgenic
for human Ig sequences is used, in vivo somatic mutagenesis) and
thus the amino acid sequences of the VH and VL regions of the
recombinant antibodies are sequences that, while derived from and
related to human germ line VH and VL sequences, may not naturally
exist within the human antibody germ line repertoire in vivo.
[0093] Such chimeric, humanized, human, and dual specific
antibodies can be produced by recombinant DNA techniques known in
the art, for example using methods described in PCT International
Application No. PCT/US86/02269; European Patent Application No.
184,187; European Patent Application No. 171,496; European Patent
Application No. 173,494; PCT International Publication No. WO
86/01533; U.S. Pat. No. 4,816,567; European Patent Application No.
125,023; Better et al. (1988) Science 240:1041-1043; Liu et al.
(1987) Proc. Natl. Acad. Sci. USA 84:3439-3443; Liu et al. (1987)
J. Immunol. 139:3521-3526; Sun et al. (1987) Proc. Natl. Acad. Sci.
USA 84:214-218; Nishimura et al. (1987) Cancer Res. 47:999-1005;
Wood et al. (1985) Nature 314:446-449; Shaw et al. (1988) J. Natl.
Cancer Inst. 80:1553-1559; Morrison (1985) Science 229:1202- 1207;
Oi et al. (1986) BioTechniques 4:214; U.S. Pat. No. 5,225,539;
Jones et al. (1986) Nature 321:552-525; Verhoeyan et al. (1988)
Science 239:1534; and Beidler et al. (1988) J. Immunol.
141:4053-4060, Queen et al. (1989) Proc. Natl. Acad. Sci. USA
86:10029-10033 (1989); U.S. Pat. No. 5,530,101; U.S. Pat. No.
5,585,089; U.S. Pat. No. 5,693,761; U.S. Pat. No. 5,693,762; WO
90/07861; and U.S. Pat. No. 5,225,539.
[0094] The term "dose" or "dosage" refers to an amount of a
substance, such as a TNF.alpha. inhibitor, which is administered to
a patient preferably using the wearable automatic injection device
of the invention. In one embodiment, the dose comprises an
effective amount, for example, including, but not limited to, 20
mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110
mg, 120 mg, 130 mg, 140 mg, 150 mg, and 160 mg, of the TNF.alpha.
inhibitor adalimumab.
[0095] The term "dosing" refers to the administration of a
substance (for example, an anti-TNF.alpha. antibody) to achieve a
therapeutic objective (for example, treatment of rheumatoid
arthritis).
[0096] The term "dosing regimen" describes a treatment schedule for
a substance, such as a TNF.alpha. inhibitor, for example, a
treatment schedule over a prolonged period of time and/or
throughout the course of treatment, for example, administering a
first dose of a TNF.alpha. inhibitor at week 0 followed by a second
dose of a TNF.alpha. inhibitor on a biweekly dosing regimen.
[0097] The term "treatment" refers to therapeutic treatment, as
well as prophylactic or suppressive measures, for the treatment of
a disorder, such as a disorder in which TNF.alpha. is detrimental,
for example, rheumatoid arthritis.
[0098] The term "patient" or "user" refers to any type of animal,
human or non-human, that may receive an administration of a
substance using exemplary automatic injection devices.
[0099] The terms "wearable automatic injection device" and
"wearable autoinjector" refer to a device worn by a patient that
enables the patient to self-administer a therapeutically effective
dose of a therapeutic agent by either fastening the wearable device
directly to his or her skin or fastening the wearable device to an
article of clothing that allows the device to interface with the
patient's body, wherein the wearable device differs from a
conventional syringe by the inclusion of a mechanism for
automatically administering the therapeutic agent to the patient's
body when the mechanism is engaged.
[0100] The terms "syringe" and "cartridge" encompass a sterile
barrel portion that is filled with a dose of a therapeutic agent
prior to distribution or sale to a patient or other non-medical
professional for administration of the therapeutic agent to a
patient. In an exemplary embodiment in which the barrel portion
forms a syringe, a distal end of the barrel portion may be coupled
to a sterile needle or multiple sterile needles. In another
exemplary embodiment in which the barrel portion forms a cartridge,
a distal end of the barrel portion may not be coupled to a sterile
needle or multiple sterile needles. In some exemplary embodiments,
a syringe may be a cartridge with a pre-attached needle or a
plurality of needles coupled to its barrel portion.
[0101] Exemplary barrel portions of a syringe or cartridge may be
formed of any suitable material including, but not limited to, a
polymer material (e.g., a medical grade polymer), metal, glass,
silicone crystals, and the like. In an exemplary embodiment, the
barrel portion may be rigid or may take the form of one or more
flexible pouches for holding the therapeutic agent.
[0102] Exemplary embodiments described herein with reference to a
syringe assembly may also be implemented using a cartridge
assembly. Similarly, exemplary embodiments described herein with
reference to a cartridge assembly may also be implemented using a
syringe assembly.
[0103] The term "vessel" refers to either a syringe or cartridge
that may be used in an exemplary wearable automatic injection
device for holding a dose of a therapeutic agent.
[0104] The term "biasing mechanism" refers to one or more
components in an automatic injection device that directly or
indirectly provide a force to a plunger and/or a bung. In an
exemplary embodiment, the biasing mechanism may include one or more
springs (e.g., a helical spring, a compression spring). The biasing
mechanism may be in a retracted state before administration of a
therapeutic agent and may be released during administration to
actuate the bung forwardly within the barrel portion. In another
exemplary embodiment, the biasing mechanism may include a chemical
gas generator, for example, an expanding foam, that is in a
non-expanded phase before administration of the therapeutic agent
and that expands during administration to actuate the bung
forwardly within the barrel portion. In other exemplary
embodiments, the biasing mechanism may employ hydraulic pressure of
working fluids, gas pressure of compressed gases, osmotic pressure,
hydrogel expansion, and the like.
[0105] The term "administration" refers to any mechanism of
delivering or administering a therapeutic agent to a patient's
body. Exemplary mechanisms or techniques of administration include,
but are not limited to, subcutaneous, intradermal, intramuscular,
topical, and the like.
[0106] The term "administration site" refers to a location on or in
a patient's body at or near which an exemplary automatic injection
device may interface with the patient for administering a
therapeutic agent.
[0107] The term "administration interface" refers to one or more
components in a wearable automatic injection device that are
inserted into, applied upon or that otherwise interface with a
patient's body to administer a dose of a therapeutic agent to the
patient. In an exemplary embodiment, the administration interface
may be directly coupled to or in contact with a syringe or a
cartridge assembly that holds the dose of the therapeutic agent. In
another exemplary embodiment, the administration interface may be
indirectly coupled to the syringe or cartridge assembly, for
example, via a piercing needle. In an exemplary embodiment, a
transfer mechanism may provide fluid communication between the
piercing needle and the administration interface. Exemplary
administration interfaces may include, but are not limited to, a
single needle, multiple needles, a needle coupled to a tubing,
multiple needles coupled to a tubing, multiple microneedles
including dissolvable microneedles, a needle-free pad, a
needle-free patch, and the like.
[0108] The terms "microneedle" and "minineedle" refer to a
miniature injection needle having any suitable dimension for the
desired technique of administering a therapeutic agent to a
patient. Exemplary microneedles may range in length from about one
micron to about 5 mm, but are not limited to this exemplary
range.
[0109] The terms "piercing needle" and "piercing needle" refer to
one or more sharp components (e.g., one or more needles and/or one
or more spikes) in a wearable automatic injection device that are
coupled to or in contact with a syringe or a cartridge assembly for
conveying a dose of a therapeutic agent from the syringe or
cartridge assembly to an administration interface which, in turn,
administers the therapeutic agent to a patient. In an exemplary
embodiment, the piercing needle is not inserted into or applied to
the patient. In another exemplary embodiment, the piercing needle
may be inserted into or applied to the patient's body.
[0110] In an exemplary wearable automatic injection device
including a syringe assembly, the piercing needle may be coupled
directly to the barrel portion of the syringe and may be in fluid
communication with the barrel portion. In an exemplary wearable
automatic injection device including a cartridge assembly, the
piercing needle may be provided separately from the barrel portion
of the cartridge, for example, within an administration interface
button or a transfer mechanism. During an administration stage, the
piercing needle may be inserted into a distal end of the barrel
portion of the cartridge to establish fluid communication between
the piercing needle and the barrel portion.
[0111] The term "pre-administration state" refers to a state of a
wearable automatic injection device prior to the start of
administration of a therapeutic agent contained in the device.
[0112] The term "administration state" refers to one or more states
of a wearable automatic injection device during the administration
of a therapeutic agent contained in the device.
[0113] The term "post-administration state" refers to completion of
administration of a therapeutically effective dose of a therapeutic
agent contained in the device and to removal of the device from the
patient prior to completion of administration of a therapeutically
effective dose of the therapeutic agent.
[0114] The term "fast" refers to an administration rate of a volume
of a therapeutic agent. In an exemplary embodiment, a volume of
about 0.1 milliliters to about 1 milliliter or more of a
therapeutic agent may be administered in an administration time
period of about one second to about twelve hours. In an exemplary
embodiment, the administration time period for the same range of
volumes may range from about one second to about thirty seconds,
but is not limited to this exemplary range. In certain exemplary
embodiments, therapeutic agent volumes of about 0.1 milliliters to
about 1 milliliter may be administered in a time duration ranging
from about 3 seconds to about 5 seconds. In certain exemplary
embodiments, therapeutic agent volumes of about 0.1 milliliters to
about 1 milliliter may be administered in time durations of or
shorter than about 20 seconds.
[0115] In certain exemplary embodiments, two or more automatic
injection devices may be coupled or used simultaneously to
administer larger volumes than 1 milliliter within time durations
ranging from about one second to about thirty seconds.
[0116] In certain exemplary embodiments, two or more cartridges may
be provided in an automatic injection device to simultaneously
administer larger volumes than 1 milliliter within time durations
ranging from about one second to about thirty seconds.
[0117] In certain exemplary embodiments, two or more syringes may
be provided in an automatic injection device to simultaneously
administer larger volumes than 1 milliliter within time durations
ranging from about one second to about thirty seconds.
[0118] The term "clothing" refers to any suitable covering on a
patient's skin to which an exemplary wearable automatic injection
device may be coupled or attached. The article of clothing may thus
form an intermediate layer between the device and the patient's
skin and may be used to indirectly couple the device to the
patient's skin. In an exemplary embodiment, the article of clothing
may be snug clothing on the patient's skin, for example, nylon
stockings. In another exemplary embodiment, the article of clothing
may be a covering on the patient's skin including, but not limited
to, a medical tape, a bandage, and the like. In another exemplary
embodiment, the article of clothing may be a coupling mechanism
that adheres the device in the proximity of the patient's skin
including, but not limited to, a sleeve that may fit round a
portion of the patient's body, a belt, a strap (e.g., a Velcro
strap), and the like.
[0119] The term "proximal," as used herein, refers to a portion,
end or component of an exemplary automatic injection device that is
farthest from an injection site on a patient's body when the device
is held against the patient for an injection or for mimicking an
injection.
[0120] The term "distal," as used herein, refers to a portion, end
or component of an exemplary automatic injection device that is
closest to an injection site on a patient's body when the device is
held against the patient for an injection or for mimicking an
injection.
[0121] The term "equal" is used herein, in a broad lay sense, to
mean exactly equal or approximately equal within some
tolerance.
II. Exemplary Automatic Injection Devices
[0122] Certain exemplary wearable automatic injection devices are
described with reference to FIGS. 1-14. Certain exemplary needle
systems that may be used in exemplary wearable automatic injection
devices to convey a therapeutic agent are described with reference
to FIGS. 15-21. Certain exemplary plunger actuation systems and
administration interface retraction systems that may be used in
exemplary wearable automatic injection devices to expel a
therapeutic agent from a syringe or cartridge are described with
reference to FIGS. 22-31. Certain exemplary administration
interface protection systems that may be used in exemplary wearable
automatic injection devices to maintain an administration interface
in a retracted position after administration in a
post-administration state are described with reference to FIGS.
32-35.
[0123] Exemplary wearable automatic injection devices may employ a
cartridge assembly (as illustrated in FIGS. 1A-1F) or a syringe
assembly (as illustrated in FIGS. 2A-2F) for holding a dose of a
therapeutic agent that may be administered to a patient through an
administration interface. In some of FIGS. 1A-1F and 2A-2F, the
administration interface is represented as a single injection
needle. However, exemplary administration interfaces are not
limited to the illustrative embodiments shown in FIGS. 1A-1F and
2A-2F.
[0124] FIGS. 1A-1F illustrate an exemplary embodiment of a wearable
automatic injection device 100 including a cartridge assembly that
may be used to administer a dose of a therapeutic agent to a
patient. FIG. 1A illustrates a first end view and a first side view
of the exemplary wearable device 100 in a packaged
pre-administration state. FIG. 1B illustrates the first end view
and the first side view of the exemplary device 100 in a
pre-administration state in which a cover covering the
administration interface is removed in preparation for
administering the dose to the patient. FIG. 1C illustrates the
first end view and the first side view of the exemplary device 100
during administration in an administration state in which the
administration interface protrudes from the housing of the device
to interface with the patient's body. FIG. 1D illustrates the first
end view and the first side view of the exemplary device 100 during
administration in an administration state in which the barrel
portion containing the dose of the therapeutic agent is deployed
forwardly within the housing of the device 100.
[0125] FIG. 1E illustrates the first end view and the first side
view of the exemplary device 100 during administration in an
administration state in which the bung is actuated by a plunger
actuator to expel the dose of the therapeutic agent from the barrel
portion. FIG. 1F illustrates the first end view and the first side
view of the exemplary device 100 after administration in a
post-administration state in which the administration interface is
retracted within the housing of the device 100.
[0126] The wearable automatic injection device 100 may include a
housing 102 that includes a plurality of walls to define an
interior portion or cavity therein for accommodating a cartridge
assembly. In an exemplary embodiment, one or more apertures or open
ends may be provided at a side wall of the housing 102 and may be
configured to receive an exemplary cartridge assembly. In an
exemplary embodiment, during assembly of the automatic injection
device, the cartridge assembly may be slid into the cavity of the
housing 102 through the aperture or open end. In an exemplary
embodiment, a cover portion may be provided for covering the
aperture or open end.
[0127] In an exemplary embodiment, the housing 102 may have an
elongated configuration, although one of ordinary skill in the art
will recognize that the housing 102 may have any suitable size,
shape and configuration for housing a barrel portion containing a
dose of a therapeutic agent to be administered to a patient. In an
exemplary embodiment, the housing 102 may be provided as a unitary
cover coupled to a base that forms the patient contact portion. In
an exemplary embodiment, the housing 102 may be formed of any
suitable material including, but not limited to, plastic and other
known materials.
[0128] The housing 102 of the wearable automatic injection device
100 may include an adhesive layer 124 disposed along a patient
contact portion at the bottom of the housing 102 that is placed
proximal to the skin of the patient or an article of clothing of
the patient. In some exemplary embodiments, the adhesive layer 124
may be configured to be placed on the body of the patient in order
to attach the housing 102 to the patient to administer the dose of
the therapeutic agent. The adhesive layer 124 may include a
non-adhesive removal mechanism 126, e.g., a tab, that is not
adhesive. The non-adhesive removal mechanism 126 may be gripped by
the patient and pulled to remove the wearable automatic injection
device 100 from the skin or clothing of the patient.
[0129] Before the wearable automatic injection device 100 is put to
use, for example, in the package state illustrated in FIG. 1A, the
adhesive layer 124 may be covered by a protective film 128 which
preserves the adhesive nature of the adhesive layer 124. The
protective film 128 may include a removal mechanism 130 which may
be gripped by the patient and pulled to remove the protective film
128 from the adhesive layer 124. This exposes the adhesive layer
124, allowing the patient to attach the housing 102 to his or her
skin or article of clothing by placing the side with the adhesive
layer 124 on the skin or the article of clothing.
[0130] The housing 102 may house a therapeutic agent cartridge
assembly extending substantially along a longitudinal axis L
between a proximal end (farthest from the administration interface)
and a distal end (nearest to the administration interface). The
cartridge assembly may include a barrel portion 106 for holding a
dose 108 of a therapeutic agent to be administered to a patient.
The barrel portion 106 may extend substantially along the
longitudinal axis between a proximal end (farthest from the
administration interface) and a distal end (nearest to the
administration interface). In an exemplary embodiment, the barrel
portion 106 may be a substantially cylindrical member having a
circular cross-section, although one of ordinary skill in the art
will recognize that the barrel portion 106 may have any suitable
shape or configuration.
[0131] In an exemplary embodiment, the barrel portion 106 may be
stationary within the housing 102 so that the administration
process does not result in the movement of the barrel portion 106
within and relative to the housing 102. In another exemplary
embodiment, the barrel portion 106 may initially, i.e., in a
pre-administration state before administration of the therapeutic
agent, be in a retracted position toward the proximal end of the
device 100 (as illustrated in FIGS. 1A-1C), and may be actuated to
an extended position toward the distal end of the device 100 in an
administration state during administration of the therapeutic
agent. A bung 110 may be provided at or near the proximal end of
the barrel portion 106 to seal the dose of the therapeutic agent
within the barrel portion 106 and to apply a force to the dose to
expel the dose from the barrel portion 106. The bung 110 may be
moveable within the barrel portion 106 toward the distal end of the
barrel portion 106 in order to expel the dose from the barrel
portion 106 in an administration state during administration of the
therapeutic agent. In an exemplary embodiment, the bung 110 may be
configured to perform both functions of sealing the dose and
squeezing the dose out of the barrel portion 106. In another
exemplary embodiment, a bung may be provided to seal the dose
within the barrel portion 106 and a separate piston or plunger rod
may be provided to impart a force to the bung in order to squeeze
the dose out of the barrel portion 106.
[0132] The cartridge assembly may include, at or near its proximal
end, a plunger actuator 112 for selectively actuating the bung 110
forwardly within the barrel portion 106 toward the distal end in
order to administer the therapeutically effective dose contained in
the barrel portion 106 to a patient. The plunger actuator 112 may
employ an energy storage and controlled energy release mechanism to
actuate the bung 110. In exemplary embodiments, the plunger
actuator 112 may be located outside the barrel portion 106 or
partly or fully within the barrel portion 106. In an exemplary
embodiment, the plunger actuator 112 may drive the bung 110
directly or indirectly though the use of a plunger disposed between
the bung 110 and the plunger actuator 112.
[0133] In an exemplary embodiment, the plunger actuator 112 may
include a biasing mechanism, for example, a spring, that is
retracted before administration and that is released during
administration to actuate the bung 110 forwardly within the barrel
portion 106. In another exemplary embodiment, the plunger actuator
112 may include a chemical gas generator, for example, an expanding
foam, that is in a non-expanded phase before administration and
that expands during administration to actuate the bung 110
forwardly within the barrel portion 106. In other exemplary
embodiments, the plunger actuator 112 may employ hydraulic pressure
of working fluids, gas pressure of compressed gases, osmotic
pressure, hydrogel expansion, and the like.
[0134] In an exemplary embodiment, the plunger actuator 112 may be
moved forwardly within the barrel portion 106 in a substantially
linear manner, i.e., substantially constant speed. This may allow
the dose to be administered to the patient at a substantially
constant administration rate. The plunger actuator 112 may include
or may be coupled to a damping mechanism that may be used to absorb
energy, for example, an initial release of energy, and to provide a
more controlled release of energy during energy release by the
plunger actuator 112. The controlled release of energy may result
in a substantially linear administration profile, i.e., a
substantially constant rate of administration of the dose over
time, and may prevent abrupt changes in the speed of the
administration.
[0135] In an exemplary embodiment, a plunger actuator 112 may
employ one or more fluid circuits containing a working fluid in
which the hydraulic pressure of the working fluid applies a force
to the bung to move the bung within the barrel portion of the
cartridge. A damping mechanism may employ a flow restrictor placed
in the fluid circuit between a source of the working fluid and the
bung.
[0136] In another exemplary embodiment, a plunger actuator 112 may
employ a biasing mechanism, for example, a spiral spring or a
helical compression spring. A damping mechanism may employ a
viscous damper, a swiss lever escapement, a runaway escapement, and
the like.
[0137] In another exemplary embodiment, a plunger actuator 112 may
employ a stepper motor connected to a gear drive system to provide
a constant linear administration profile.
[0138] The cartridge assembly may include, at or near its distal
end, a cartridge stopper 114 that may include a septum and a cover
115 for the septum. The septum may be a pierceable layer of
material that is disposed adjacent to the distal end of the barrel
portion 106 in order to seal the dose in the barrel portion 106.
When intact, the septum may seal the dose within the barrel portion
106. When pierced by a sharp component, for example, a piercing
needle, the septum may allow the dose to leave the barrel portion
106 and enter the piercing needle. The septum may be formed of a
material that may be pierced by a piercing needle. A cover may be
provided to protectively cover the septum from accidental piercing
by the piercing needle when the device 100 is in the packaged
pre-administration state as illustrated in FIG. 1A. In an exemplary
embodiment, the cartridge stopper 114 may also include a cover to
protectively cover a piercing needle provided in the vicinity of
the cartridge stopper 114, thereby preventing accidental piercing
of the septum by the piercing needle when the device 100 is in the
packaged pre-administration state as illustrated in FIG. 1A.
[0139] The housing 102 of the wearable automatic injection device
100 may also house an administration interface button 116 bearing
an administration interface 118 that is configured to pierce the
patient's skin. In an exemplary embodiment, the administration
interface 118 may be aligned orthogonally to the longitudinal axis
L of the device 100. In an exemplary embodiment, the administration
interface 118 may be held in place by an administration interface
carrier (not pictured) provided in the administration interface
button 116 or separately from the administration interface button
116.
[0140] In some exemplary embodiments, the administration interface
118 may include one or more injection needles having any suitable
size, shape and configuration suitable for piercing the skin of the
patient to administer a therapeutic agent. In an exemplary
embodiment, the administration interface 118 may include a single
injection needle (shown as a continuous line in FIGS. 1A-1F). In
another exemplary embodiment, the administration interface 218 may
include two or more injection needles (the additional needles shown
as dashed lines in FIGS. 1A-1F). In some other exemplary
embodiments, the administration interface 118 may include a
needle-free pad and/or a needle-free patch for performing a topical
administration of a therapeutic agent.
[0141] Suitable injection needles that may be used in exemplary
administration interfaces may have a length configured or selected
to provide an administration depth suitable for the desired
therapy. Subcutaneous injections typically penetrate about six to
ten millimeters into the skin. In an exemplary embodiment,
exemplary injection needles may have a length of about twelve mm
and may be administered to a depth of about seven mm into the skin.
In other exemplary embodiments, exemplary injection needles may
have lengths suitable for intradermal, intramuscular therapies, and
the like.
[0142] Suitable injection needles may have a wall thickness
suitable to provide sufficient mechanism strength, a diameter
suitable to allow a desired flow rate of the substance while
minimizing patient sensation, and a tip geometry suitable for the
desired therapy while minimizing patient sensation.
[0143] Exemplary injection needles may be coated as needed to
minimize patient sensation as allowed by therapy. The
administration interface 118 may be covered, protected from
mechanical damage and maintained in a sterile or septic condition
by an administration interface cover 122, for example, a rigid
needle shield, a soft needle shield, or both. The administration
interface cover 122 may also maintain sterility of the fluid
conduit formed by and coupled to the administration interface
118.
[0144] The administration interface button 116 may also bear a
piercing needle 120 configured to pierce the septum and establish
fluid communication with the barrel portion 106. In an exemplary
embodiment, the piercing needle 120 may be aligned parallel to the
longitudinal axis L of the device 100. The piercing needle 120 may
have any suitable size, shape and configuration suitable for
piercing the septum and is not limited to the illustrative
embodiment.
[0145] In an exemplary embodiment, the administration interface 118
and the piercing needle 120 may be coupled to and in fluid
communication with each other via the body of the administration
interface button 116. In another exemplary embodiment, the
administration interface 118 and the piercing needle 120 may be
coupled to and in fluid communication with each other via one or
more fluid conduits (not pictured). In another exemplary
embodiment, the administration interface 118 and the piercing
needle 120 may be directly coupled to and in fluid communication
with each other.
[0146] In an exemplary embodiment, in a pre-administration state
before administration of the therapeutic agent, the administration
interface button 116 may be in a vertically raised position
relative to the housing 102 such that the administration interface
button 116 protrudes from the top of the housing 102, as
illustrated in FIGS. 1A and 1B. In this position, the
administration interface 118 may be retracted within the housing
102 and may not be applied to the patient's body. In this position,
the piercing needle 120 may be aligned vertically above the septum
in the cartridge stopper 114 and may not pierce the septum. At the
beginning of the administration process, the administration
interface button 116 may be pressed downward, for example, by a
user of the device or automatically. This may push the
administration interface button 116 to a vertically depressed
position relative to the housing 102 closer to the patient's body
such that the administration interface button 116 no longer
protrudes from the top of the housing 102, as illustrated in FIGS.
1C-1E. In this position, the administration interface 118 may
protrude from the bottom of the housing 102 and may be inserted
into or applied to the patient's body. In this position, the
piercing needle 120 may be aligned with the septum in the cartridge
stopper 114 and may pierce the septum.
[0147] In an exemplary embodiment, the septum may initially be
spaced from the administration interface button 116. In this
embodiment, the piercing needle 120 may pierce the septum when the
cartridge stopper 114 bearing the septum is advanced within the
housing 102 toward the administration interface button 116. That
is, in a pre-administration state before administration of the
therapeutic agent, the piercing needle 120 may be spaced from the
septum such that there is no fluid communication between the barrel
portion 106 and the administration interface 118 coupled to the
administration interface button 116. In an administration state,
the barrel portion 106 may advance within the housing 102 toward
the distal end of the device 100 so that the piercing needle 120
may pierce the septum and establish fluid communication between the
barrel portion 106 and the administration interface 118 coupled to
the administration interface button 116. This fluid communication
may allow the dose of the therapeutic agent to flow from the barrel
portion 106 to the patient through the piercing needle 120 and the
administration interface 118 when pressure is applied to the dose
by the bung 110 in an administration state during administration of
the therapeutic agent.
[0148] Referring now to FIG. 1F, in an exemplary embodiment, the
housing 102 of the wearable automatic injection device 100 may
include a skin sensor foot 132, which is a structure housed under
or in the portion of the housing 102 proximal to the administration
site on or in the patient's body. Prior to and during
administration of the therapeutic agent, the skin sensor foot 132
is retained within or forms a portion of the underside of the
housing 102. When the wearable automatic injection device 100 is
attached to the administration site on or in the patient's body and
activated, the skin sensor foot 132 may be free to move but may be
constrained by the administration site. When the wearable automatic
injection device 100 is removed from the administration site,
regardless of whether the administration of the therapeutic agent
was completed, the skin sensor foot 132 is no longer constrained,
and extends and projects outside the periphery of the housing 102.
This, in turn, activates a retraction trigger. When the retraction
trigger is activated, a retraction mechanism retracts the
administration interface 120 which may also raise the
administration interface button 116 from the vertically lowered
position to the vertically raised position, so that the
administration interface button 116 protrudes from the top of the
housing 102 and the administration interface 118 is retracted
within the housing 102.
[0149] FIG. 1A illustrates the wearable automatic injection device
100 in a pre-administration state, for example, as packaged, in
which the barrel portion 106 may be pre-filled and/or pre-fillable
with the dose 108 of the therapeutic agent and in a retracted
position ready for use. The barrel portion 106 may contain the dose
108 of the therapeutic agent in the interior space defined between
the wall or walls of the barrel portion 106 and the bung 110. In an
embodiment, the plunger actuator 112 may store energy that, when
released, may actuate the bung 110. The administration interface
button 116 may be partially disposed within the housing 102 at the
vertically raised position above the administration site, and the
administration interface 118 may be retracted within the housing
102. The protrusion of the administration interface button 116 out
of the top of the housing 102 may provide a visual indication to
the patient that the wearable automatic injection device 100 is not
in operation.
[0150] FIG. 1B illustrates the wearable automatic injection device
100 in a pre-administration state in which the administration
interface cover 122 and the septum cover are removed. In exemplary
embodiments, the protective film 128 may include a linking member
that is connected to the administration interface cover 122 and the
septum and piercing needle covers in the cartridge stopper 114. The
linking member may include a tether, a tab or other linkage
mechanism. When the protective film 128 is removed, the linking
member of the protective film 128 may remove the administration
interface cover 122 and the septum and piercing needle covers in
the cartridge stopper 114.
[0151] FIG. 1C illustrates the wearable automatic injection device
100 in an administration state during administration of the
therapeutic agent in which the administration interface button 116
is in the vertically lowered position within the housing 102. In
the vertically lowered position, the administration interface
button 116 may be disposed within the housing 102 at a depressed or
vertically lowered location above the administration site, and the
administration interface 118 may project from the housing 102
through one or more apertures or open ends in the housing 102 so
that it can interface with the patient's body at the administration
site. In an exemplary embodiment, a cover portion may be provided
for covering the aperture or open end. In an exemplary embodiment,
the aperture or open end of the housing may oppose the patient
contact portion of the housing such that the administration
interface button 116 may be vertically lowered to administer the
therapeutic agent. In the vertically lowered state, the
administration interface button 116 may not protrude from the top
of the housing 102, which may provide a visual indication to the
patient that the wearable automatic injection device 100 is in
operation. In another exemplary embodiment, the aperture or open
end in the housing 102 may not be disposed opposing the patient
contact portion and may instead be disposed in a side wall of the
housing. The administration interface button 116 may be moved
laterally or horizontally in some exemplary embodiments to
administer the therapeutic agent.
[0152] FIG. 1D illustrates the wearable automatic injection device
100 in an administration state during administration of the
therapeutic agent in which the barrel portion 106 containing the
dose 108 of the therapeutic agent is deployed forwardly from a
retracted position to an extended position within the housing of
the device 100. The advancement of the barrel portion 106 may bring
the distal end of the barrel portion 106 or the cartridge stopper
114 in the vicinity of or in contact with the administration
interface button 116. In an exemplary embodiment, the piercing
needle 120 may pierce the septum held in the cartridge stopper 114
in order to establish fluid communication between the barrel
portion 106 and the administration interface 118.
[0153] FIG. 1E illustrates the wearable automatic injection device
100 in an administration state during administration of the
therapeutic agent in which the plunger actuator 112 is triggered to
move the bung 110. Triggering of the plunger actuator 112 may
release stored energy in the plunger actuator 112 in order to move
the bung 110 within the barrel portion 106 toward the distal end of
the device 100. The movement of the bung 110 may eject the dose of
the therapeutic agent from the barrel portion 106 through the
distal end of the barrel portion 106. Any suitable mechanism may be
used to trigger the plunger actuator 112 including, but not limited
to, a linking member that is coupled to and activated by the
depression of the administration interface button 116 or by the
removal of the administration interface cover 122, a trigger button
that may be activated by the patient, and the like.
[0154] FIG. 1F illustrates the wearable automatic injection device
100 in a post-administration state, for example, after
administering a therapeutically effective dose of the therapeutic
agent or removal of the wearable automatic injection device 100
from the patient before administration of a therapeutically
effective dose of the therapeutic agent, in which the
administration interface button 116 is in the vertically raised
position. In the vertically raised position, the administration
interface button 116 may be disposed partly within the housing 102
at an elevated or vertically raised location above the
administration site, and the administration interface 118 may be
retracted within the housing 102. A portion of the administration
interface button 116 may project from the top of the housing 102 to
provide a visual indication to the patient that the wearable
automatic injection device assembly 100 is not in operation (i.e.,
in a post-administration state). The barrel portion 106 may be
empty of the therapeutic agent and the plunger actuator 112 may no
longer store energy. A skin sensor foot 132 may extend from the
bottom of the housing 102 upon removal of the device 100 from the
administration site.
[0155] The housing 102 may include a retraction mechanism that
automatically raises the administration interface button 116 from
the vertically lowered administration state (shown in FIGS. 1C-1E)
to the vertically raised post-administration state (shown in FIG.
1F). In an exemplary embodiment, the retraction mechanism may
include a biasing mechanism, for example, a spring, that biases the
cartridge assembly away from the administration site when the
retraction mechanism is triggered.
[0156] A retraction trigger, when activated, may trigger the
retraction mechanism in order to raise the administration interface
button 116 from the vertically lowered state to the vertically
raised state. In an exemplary embodiment, the bung 110 and/or the
plunger actuator 112 may include a linking member connected to the
retraction trigger. The linking member may include a tether, a tab
or other linkage mechanism. The linking member may be of a suitable
length such that, when the bung 110 has been moved to the end of
the barrel portion 106 (in order to administer a dose of the
therapeutic agent), the linking member triggers a latch that in
turn activates the retraction trigger. In another exemplary
embodiment, the extension of the skin sensor foot 132 from the
bottom of the housing 102 may activate the retraction trigger.
[0157] In an exemplary embodiment, the retraction mechanism may
include an end-of-dose retraction trigger that, when activated,
triggers the retraction mechanism The end-of-dose retraction
trigger may be activated when the therapeutically effective dose of
therapeutic agent in the wearable automatic injection device 100 is
administered. In an exemplary embodiment, the end-of-dose
retraction trigger may include a latch, for example, a flexible
plastic hook, that is released upon completed administration of the
therapeutic agent. The retraction mechanism may also include an
early-removal retraction trigger that, when activated, triggers the
retraction mechanism. The early-removal retraction trigger may be
activated when the wearable automatic injection device 100 is
removed from the administration site before the therapeutically
effective dose of therapeutic agent is completely administered. In
an exemplary embodiment, the early-removal retraction trigger may
include a latch, for example, a flexible plastic hook, that is
released upon removal of the wearable automatic injection device
100 from the administration site. The retraction mechanism is
responsive to the end-of-dose retraction trigger and responsive to
the early-removal retraction trigger to automatically retract the
cartridge assembly from the administration site.
[0158] In an exemplary embodiment, raising of the administration
interface button 116 to the vertically raised position may cause
the piercing needle 120 to bend upward, thus preventing undesirable
reuse of the piercing needle and the wearable automatic injection
device.
[0159] FIGS. 2A-2F illustrate an exemplary embodiment of a wearable
automatic injection device 200 including a syringe assembly that
may be used to administer a dose of a therapeutic agent to a
patient. FIG. 2A illustrates a first end view and a first side view
of the exemplary wearable device 200 in a packaged
pre-administration state. FIG. 2B illustrates the first end view
and the first side view of the exemplary device 200 in a
pre-administration state in which a cover covering the
administration interface is removed in preparation for
administration a therapeutic agent. FIG. 2C illustrates the first
end view and the first side view of the exemplary device 200 in an
administration state during administration of the therapeutic agent
in which the administration interface protrudes from the housing of
the device to interface with the patient's body FIG. 2D illustrates
the first end view and the first side view of the exemplary device
200 in an administration state during administration of the
therapeutic agent in which the barrel portion containing the dose
of the therapeutic agent is deployed forwardly within the housing
of the device 200. FIG. 2E illustrates the first end view and the
first side view of the exemplary device 200 in an administration
state during administration of the therapeutic agent in which the
bung is actuated by a plunger actuator to expel the dose of the
therapeutic agent from the barrel portion. FIG. 2F illustrates the
first end view and the first side view of the exemplary device 200
in an post-administration state after administration of the
therapeutic agent in which the administration interface is
retracted within the housing of the device 200.
[0160] The wearable automatic injection device 200 may include a
housing 202 for accommodating an exemplary syringe assembly. The
wearable automatic injection device 200 may include a housing 202
that includes a plurality of walls to define an interior portion or
cavity therein for accommodating a syringe assembly. In an
exemplary embodiment, one or more apertures or open ends may be
provided at a side wall of the housing 202 and may be configured to
receive an exemplary syringe assembly. In an exemplary embodiment,
during assembly of the automatic injection device, the syringe
assembly may be slid into the cavity of the housing 202 through the
aperture or open end. In an exemplary embodiment, a cover portion
may be provided for covering the aperture or open end.
[0161] In an exemplary embodiment, the housing 202 may have an
elongated configuration, although one of ordinary skill in the art
will recognize that the housing 202 may have any suitable size,
shape and configuration for housing a barrel portion containing a
dose of a therapeutic agent to be administered to a patient. In an
exemplary embodiment, the housing 202 may be provided as a unitary
cover coupled to a base that forms the patient contact portion. In
an exemplary embodiment, the housing 202 may be formed of any
suitable material including, but not limited to, plastic and other
known materials.
[0162] The housing 202 of the wearable automatic injection device
200 may include an adhesive layer 224 disposed along a patient
contact portion at the bottom of the housing 202 that is placed
proximal to the skin of the patient or an article of clothing of
the patient. In some exemplary embodiments, the adhesive layer 224
may be configured to be placed on the skin of the patient in order
to attach the housing 202 to the patient to administer the dose of
the therapeutic agent. The adhesive layer 224 may include a
non-adhesive removal mechanism 226, e.g., a tab, that is not
adhesive. The non-adhesive removal mechanism 226 may be gripped by
the patient and pulled to remove the wearable automatic injection
device 200 from the skin or clothing of the patient.
[0163] Before the wearable automatic injection device 200 is put to
use, for example, in the package state illustrated in FIG. 2A, the
adhesive layer 224 may be covered by a protective film 228 which
preserves the adhesive nature of the adhesive layer 224. The
protective film 228 may include a removal mechanism 230, e.g., a
tab, which may be gripped by the patient and pulled to remove the
protective film 228 from the adhesive layer 224. This exposes the
adhesive layer 224, allowing the patient to attach the housing 202
to his or her skin or article of clothing by placing the side with
the adhesive layer 224 on the skin or the article of clothing.
[0164] The housing 202 may house a syringe assembly extending
substantially along a longitudinal axis L between a proximal end
(farthest from the administration interface) and a distal end
(nearest to the administration interface). The syringe assembly may
include a barrel portion 206 for holding a dose 208 of a
therapeutic agent to be administered to a patient. The barrel
portion 206 may extend substantially along the longitudinal axis
between a proximal end (farthest from the administration interface)
and a distal end (nearest to the administration interface). In an
exemplary embodiment, the barrel portion 206 may be a substantially
cylindrical member having a circular cross-section, although one of
ordinary skill in the art will recognize that the barrel portion
206 may have any suitable shape or configuration.
[0165] In an exemplary embodiment, the barrel portion 206 may be
stationary within the housing 202 so that the administration
process does not result in the movement of the barrel portion 206
within and relative to the housing 202. In another exemplary
embodiment, the barrel portion 206 may initially, i.e., in a
pre-administration state before administration of the therapeutic
agent, be in a retracted position toward the proximal end of the
device 200 (as illustrated in FIGS. 2A-2C), and may be actuated to
an extended position toward the distal end of the device 200 in an
administration state during administration of the therapeutic
agent.
[0166] A bung 210 may be provided at or near the proximal end of
the barrel portion 206 to seal the dose of the therapeutic agent
within the barrel portion 206 and to apply a force to the dose to
expel the dose from the barrel portion 206. The bung 210 may be
moveable within the barrel portion 206 toward the distal end of the
barrel portion 206 in order to expel the dose from the barrel
portion 206 in an administration state during administration of the
therapeutic agent. In an exemplary embodiment, the bung 210 may be
configured to perform both functions of sealing the dose and
squeezing the dose out of the barrel portion 206. In another
exemplary embodiment, a bung may be provided to seal the dose
within the barrel portion 206 and a separate piston may be provided
to impart a force to the bung in order to squeeze the dose out of
the barrel portion 206.
[0167] The syringe assembly may include, at or near its distal end,
a syringe stopper or a distal portion of the syringe 214 that may
include a piercing needle 220. The piercing needle 220 may be
covered, protected from mechanical damage and maintained in aseptic
condition, i.e., sterile condition, by a piercing needle cover 234,
for example, a soft needle shield, a rigid needle shield, or both.
The piercing needle cover 234 may also maintain sterility of the
fluid conduit formed by and coupled to the piercing needle 220. In
an exemplary embodiment, the piercing needle 220 may be aligned
parallel to the longitudinal axis L of the device 200. The piercing
needle 220 may have any suitable size, shape and configuration
suitable for piercing the septum, and is not limited to the
illustrative embodiment.
[0168] The syringe assembly may include, at or near its proximal
end, a plunger actuator 212 for selectively actuating the bung 210
forwardly within the barrel portion 206 toward the distal end in
order to administer the therapeutically effective dose contained in
the barrel portion 206 to a patient. The plunger actuator 212 may
employ an energy storage and controlled energy release mechanism to
actuate the bung 210. In exemplary embodiments, the plunger
actuator 212 may be located outside the barrel portion 206 or
partly or fully within the barrel portion 206. In exemplary
embodiments, the plunger actuator 212 may drive the bung 210
directly or indirectly though the use of a plunger disposed between
the bung 210 and the plunger actuator 212.
[0169] In an exemplary embodiment, the plunger actuator 212 may
include a biasing mechanism, for example, a spring, that is
retracted before administration of the therapeutic agent and that
is released during administration to actuate the bung 210 forwardly
within the barrel portion 206. In another exemplary embodiment, the
plunger actuator 212 may include a chemical gas generator, for
example, an expanding foam, that is in a non-expanded phase before
administration of the therapeutic agent and that expands during
administration to actuate the bung 210 forwardly within the barrel
portion 206. In other exemplary embodiments, the plunger actuator
212 may employ hydraulic pressure of working fluids, gas pressure
of compressed gases, osmotic pressure, hydrogel expansion, and the
like.
[0170] In an exemplary embodiment, the plunger actuator 212 may be
moved forwardly within the barrel portion 206 in a substantially
linear manner, i.e., substantially constant speed. This may allow
the dose to be administered to the patient at a substantially
constant administration rate. The plunger actuator 212 may include
or may be coupled to a damping mechanism that may be used to absorb
energy, for example, an initial release of energy, and to provide a
more controlled release of energy during energy release by the
plunger actuator 212. The controlled release of energy may result
in a substantially linear administration profile, i.e., a
substantially constant rate of administration of the dose over
time, and may prevent abrupt changes in the speed of the
administration. In an exemplary embodiment, a plunger actuator 212
may employ the hydraulic pressure of a working fluid and a damping
mechanism may employ a flow restrictor placed in a fluid pathway
between the working fluid and the bung 210. In another exemplary
embodiment, a plunger actuator 212 may employ a biasing mechanism
and a damping mechanism may employ a viscous damper, a swiss lever
escapement, a runaway escapement, and the like. In another
exemplary embodiment, a plunger actuator 212 may employ a stepper
motor connected to a gear drive system to provide a constant linear
administration profile.
[0171] The housing 202 of the wearable automatic injection device
200 may also house an administration interface button 216 bearing
an administration interface 218 that is configured to administer a
therapeutic agent on, in or through the skin to any desired depth.
In an exemplary embodiment, the administration interface 218 may be
aligned orthogonally to the longitudinal axis L of the device 200.
In an exemplary embodiment, the administration interface 218 may be
held in place by an administration interface carrier (not pictured)
provided in the administration interface button 216 or separately
from the administration interface button 216.
[0172] In some exemplary embodiments, the administration interface
218 may include one or more injection needles that may have any
suitable size, shape and configuration suitable for piercing the
skin of the patient to administer the therapeutic agent, and is not
limited to the illustrative embodiment. In an exemplary embodiment,
the administration interface 218 may include a single injection
needle (shown as a continuous line in FIGS. 2A-2F). In another
exemplary embodiment, the administration interface 218 may include
two or more injection needles (the additional needles shown as
dashed lines in FIGS. 2A-2F). In some other exemplary embodiments,
the administration interface 218 may include a needle-free pad
and/or a needle-free patch for performing a topical administration
of a therapeutic agent.
[0173] Suitable injection needles that may be used in exemplary
administration interfaces may have a length configured or selected
to provide an administration depth suitable for the desired
therapy. Subcutaneous injections typically penetrate about six to
ten millimeters into the skin. In an exemplary embodiment,
exemplary injection needles may have a length of about twelve mm
and may be administered to a depth of about seven mm into the skin.
In other exemplary embodiments, exemplary injection needles may
have lengths suitable for intradermal, intramuscular therapies, and
the like. Suitable injection needles may have a wall thickness
suitable to provide sufficient mechanism strength, a diameter
suitable to allow a desired flow rate of the substance while
minimizing patient sensation, and a tip geometry suitable for the
desired therapy while minimizing patient sensation.
[0174] Exemplary injection needles may be coated as needed to
minimize patient sensation as allowed by therapy. The
administration interface 218 may be covered, protected from
mechanical damage and maintained in aseptic condition, i.e.,
sterile condition, by an administration interface cover 222, for
example, a rigid needle shield, a soft needle shield, or both. The
administration interface cover 222 may also maintain sterility of
the fluid conduit formed by and connected to the administration
interface 218.
[0175] The administration interface button 216 may also include a
pierceable septum disposed in the vicinity of the piercing needle
220. In a pre-administration state, the piercing needle 220 does
not pierce the septum, thus prevent fluid communication between the
barrel portion 206 and the piercing needle 220. In an
administration state, when pierced by a sharp component, for
example, the piercing needle 220, the septum may allow the dose to
leave the barrel portion 206 and enter the piercing needle 220. In
an exemplary embodiment, one or more covers 215 may enclose the
septum in a sterility barrier. The covers 215 may be pierced when
the piercing needle 220 pierces the septum.
[0176] In an exemplary embodiment, the administration interface 218
and the piercing needle 220 may be coupled to and in fluid
communication with each other via the body of the administration
interface button 216. In another exemplary embodiment, the
administration interface 218 and the piercing needle 220 may be
coupled to and in fluid communication with each other via one or
more fluid conduits (not pictured). In another exemplary
embodiment, the administration interface 218 and the piercing
needle 220 may be directly coupled to and in fluid communication
with each other.
[0177] In an exemplary embodiment, before administration in a
pre-administration state, the administration interface button 216
may be in a vertically raised position relative to the housing 202
such that the administration interface button 216 protrudes from
the top of the housing 202, as illustrated in FIGS. 2A and 2B. In
this position, the administration interface 218 may be retracted
within the housing 202 and may not interface with the patient's
body. In this position, the piercing needle 220 may be aligned
vertically below the septum in the syringe stopper 214 and may not
pierce the septum. At the beginning of the administration process,
the administration interface button 216 may be pressed downward,
for example, by a user of the device or automatically. This may
push the administration interface button 216 to a vertically
depressed position relative to the housing 202 closer to the
patient's body such that the administration interface button 216 no
longer protrudes from the top of the housing 202, as illustrated in
FIGS. 2C-2E. In this position, the administration interface 218 may
protrude from the bottom of the housing 202 and may be interface
with the patient's body, e.g., by penetrating the patient's body.
In this position, the piercing needle 220 may be aligned with the
septum in the syringe stopper 214 and may pierce the septum.
[0178] In an exemplary embodiment, the septum may initially be
spaced from the administration interface button 216. In this
embodiment, the piercing needle 220 may pierce the septum when the
syringe stopper 214 bearing the piercing needle 220 is advanced
within the housing 202 toward the septum. That is, before
administration in a pre-administration state, the piercing needle
220 may be spaced from the septum such that there is no fluid
communication between the barrel portion 206 and the administration
interface 218 coupled to the administration interface button 216.
In an administration state, the barrel portion 206 may advance
within the housing 202 toward the distal end of the device 200 such
that that the piercing needle 220 may pierce the septum and
establish fluid communication between the barrel portion 206 and
the administration interface 218 coupled to the administration
interface button 216. This fluid communication may allow the dose
of the therapeutic agent to flow from the barrel portion 206 to the
patient through the piercing needle 220 and the administration
interface 218 when pressure is applied to the dose by the bung 210
during administration in an administration state.
[0179] Referring now to FIG. 2F, in an exemplary embodiment, the
housing 202 of the wearable automatic injection device 200 may
include a skin sensor foot 232, which is a structure housed under
or in the portion of the housing 202 proximal to the administration
site. Prior to administration of the therapeutic agent and during
administration, the skin sensor foot 232 is retained within or
forms a portion of the underside of the housing 202. When the
wearable automatic injection device 200 is attached to the
administration site and activated, the skin sensor foot 232 may be
free to move but may be constrained by the administration site.
When the wearable automatic injection device 200 is removed from
the administration site, regardless of whether administration of
the therapeutic agent was completed, the skin sensor foot 232 is no
longer constrained, and extends and projects outside the periphery
of the housing 202. This, in turn, activates a retraction trigger.
When the retraction trigger is activated, a retraction mechanism
retracts the administration interface 220 which may also raise the
administration interface button 216 from the vertically lowered
position to the vertically raised position, so that the
administration interface button 216 protrudes from the top of the
housing 202 and the administration interface 218 is retracted
within the housing 202.
[0180] FIG. 2A illustrates the wearable automatic injection device
200 in a pre-administration state, for example, as packaged, in
which the barrel portion 206 may be pre-filled with the dose 208 of
the therapeutic agent and in a retracted position ready for use.
The barrel portion 206 may contain the dose 208 of the therapeutic
agent in the interior space defined between the wall or walls of
the barrel portion 206 and the bung 210. In an embodiment, the
plunger actuator 212 may store energy that, when released, may
actuate the bung 210. The administration interface button 216 may
be partially disposed within the housing 202 at the vertically
raised position above the administration site, and the
administration interface 218 may be retracted within the housing
202. The protrusion of the administration interface button 216 out
of the top of the housing 202 may provide a visual indication to
the patient that the wearable automatic injection device 200 is not
in operation.
[0181] FIG. 2B illustrates the wearable automatic injection device
200 in a pre-administration state before administration of the
therapeutic agent in which the administration interface cover 222
and the septum cover are removed. In exemplary embodiments, the
protective film 228 may include a linking member that is connected
to the administration interface cover 222, the septum cover and the
piercing needle cover in the syringe stopper 224. The linking
member may include a tether, a tab or other linkage mechanism. When
the protective film 228 is removed, the linking member of the
protective film 228 may automatically remove the administration
interface cover 222, the septum cover and the piercing needle cover
in the syringe stopper 214.
[0182] FIG. 2C illustrates the wearable automatic injection device
200 in an administration state during administration of the
therapeutic agent in which the administration interface button 216
is in the vertically lowered position within the housing 202. In
the vertically lowered position, the administration interface
button 216 may be disposed within the housing 202 at a depressed or
vertically lowered location above the administration site, and the
administration interface 218 may project from the housing 202
through one or more apertures or open ends in the housing 202 so
that it can interface with the patient's body at the administration
site. In an exemplary embodiment, a cover portion may be provided
for covering the aperture or open end. In an exemplary embodiment,
the aperture or open end of the housing may oppose the patient
contact portion of the housing such that the administration
interface button 216 may be vertically lowered to administer the
therapeutic agent. In the vertically lowered state, the
administration interface button 216 may not protrude from the top
of the housing 202, which may provide a visual indication to the
patient that the wearable automatic injection device 200 is in
operation. In another exemplary embodiment, the aperture or open
end in the housing 202 may not be disposed opposing the patient
contact portion and may instead be disposed in a side wall of the
housing. The administration interface button 216 may be moved
laterally or horizontally in some exemplary embodiments to
administer the therapeutic agent.
[0183] FIG. 2D illustrates the wearable automatic injection device
200 in an administration state during administration of the
therapeutic agent in which the barrel portion 206 containing the
dose 208 of the therapeutic agent is deployed forwardly from a
retracted position to an extended position within the housing of
the device 200. The advancement of the barrel portion 206 may bring
the distal end of the barrel portion 206 or the syringe stopper 214
in the vicinity of or in contact with the administration interface
button 216. In an exemplary embodiment, the piercing needle 220 may
pierce the septum held in the syringe stopper 214 in order to
establish fluid communication between the barrel portion 206 and
the administration interface 218.
[0184] FIG. 2E illustrates the wearable automatic injection device
200 in an administration state during administration of the
therapeutic agent in which the plunger actuator 212 is triggered to
move the bung 210. Triggering of the plunger actuator 212 may
release stored energy in the plunger actuator 212 in order to move
the bung 210 within the barrel portion 206 toward the distal end of
the device 200. The movement of the bung 210 may eject the dose of
the therapeutic agent from the barrel portion 206 through the
distal end of the barrel portion 206. Any suitable mechanism may be
used to trigger the plunger actuator 212 including, but not limited
to, a linking member that is coupled to and activated by the
depression of the administration interface button 216 or by the
removal of the administration interface cover 222, a trigger button
that may be activated by the patient, and the like.
[0185] FIG. 2F illustrates the wearable automatic injection device
200 in a post-administration state after administration of a
therapeutic agent, for example, after administering a
therapeutically effective dose of the therapeutic agent or removal
of the wearable automatic injection device 200 from the patient
before administration of a therapeutically effective dose of the
therapeutic agent, in which the administration interface button 216
is in the vertically raised position. In the vertically raised
position, the administration interface button 216 may be disposed
partly within the housing 202 at an elevated or vertically raised
location above the administration site, and the administration
interface 218 may be retracted within the housing 202. A portion of
the administration interface button 216 may project from the top of
the housing 202 to provide a visual indication to the patient that
the wearable automatic injection device assembly 200 is not in
operation (i.e., in a post-administration state). The barrel
portion 206 may be empty of the therapeutic agent and the plunger
actuator 212 may no longer store energy. A skin sensor foot 232 may
extend from the bottom of the housing 202 upon removal of the
device 200 from the administration site.
[0186] The housing 202 may include a retraction mechanism that
automatically raises the administration interface button 216 from
the vertically lowered administration state (shown in FIGS. 2C-2E)
to the vertically raised post-administration state (shown in FIG.
2F). In an exemplary embodiment, the retraction mechanism may
include a biasing mechanism, for example, a spring, that biases the
syringe assembly away from the administration site when the
retraction mechanism is triggered.
[0187] A retraction trigger, when activated, may trigger the
retraction mechanism in order to raise the administration interface
button 216 from the vertically lowered state to the vertically
raised state. In an exemplary embodiment, the bung 210 and/or the
plunger actuator 212 may include a linking member connected to the
retraction trigger. The linking member may include a tether, a tab
or other linkage mechanism. The linking member may be of a suitable
length such that, when the bung 210 has been moved to the end of
the barrel portion 206 (in order to administer a dose of the
therapeutic agent), the linking member triggers a latch that in
turn activates the retraction trigger. In another exemplary
embodiment, the extension of the skin sensor foot 232 from the
bottom of the housing 202 may activate the retraction trigger.
[0188] In an exemplary embodiment, the retraction mechanism may
include an end-of-dose retraction trigger that, when activated,
triggers the retraction mechanism The end-of-dose retraction
trigger may be activated when the therapeutically effective dose of
therapeutic agent in the wearable automatic injection device 200 is
administered. In an exemplary embodiment, the end-of-dose
retraction trigger may include a latch, for example, a flexible
plastic hook, that is released upon completed administration of the
therapeutic agent. The retraction mechanism may also include an
early-removal retraction trigger that, when activated, triggers the
retraction mechanism. The early-removal retraction trigger may be
activated when the wearable automatic injection device 200 is
removed from the administration site before the therapeutically
effective dose of therapeutic agent is completely administered. In
an exemplary embodiment, the early-removal retraction trigger may
include a latch, for example, a flexible plastic hook, that is
released upon removal of the wearable automatic injection device
200 from the administration site. The retraction mechanism is
responsive to the end-of-dose retraction trigger and responsive to
the early-removal retraction trigger to automatically retract the
syringe assembly from the administration site.
[0189] In an exemplary embodiment, raising of the administration
interface button 216 to the vertically raised position may cause
the piercing needle 220 to bend upward, thus preventing undesirable
reuse of the piercing needle and the wearable automatic injection
device 200.
[0190] In exemplary embodiments, the barrel portion of the wearable
automatic injection device 100 (in FIG. 1)/200 (in FIG. 2) may be
pre-filled with any suitable volume of a therapeutic agent. In an
exemplary embodiment, the barrel portion 106 may be pre-filled with
a volume of between about 0.1 milliliters and about 3.0
milliliters, although exemplary devices are not limited to this
exemplary range of therapeutic agent volumes. In an exemplary
embodiment in which the volume to be administered is larger than
the capacity of the barrel portion of the device, two or more
barrel portions may be provided in the device for holding the
entire volume of the therapeutic agent. Other components in the
device may be configured to eject the therapeutic agent from the
multiple barrel portions out through an administration interface
for administration to the patient. In another exemplary embodiment,
two or more automatic injection devices, each including a barrel
portion, may be provided to administer the entire volume of the
therapeutic agent.
[0191] In exemplary embodiments, the wearable automatic injection
device 100 (in FIG. 1)/200 (in FIG. 2) may be used to administer a
therapeutically effective amount of therapeutic agent over a period
of time ranging from about twenty seconds to about twelve hours.
Certain other exemplary embodiments provide actuation devices and
systems that cause actuation of the syringe plunger at fast rate in
order to administer the therapeutic agent to a patient at a fast
rate. Exemplary fast embodiments may administer therapeutic agent
volumes of about 0.5 milliliters to about 1 milliliter in about one
second to about twenty seconds, although exemplary administration
rates are not limited to this exemplary range.
[0192] Exemplary embodiments may provide a linear administration
profile for the therapeutic agent so that the administration rate
is substantially constant over time. In some cases, a linear
administration profile may reduce discomfort experienced by the
patient. In an exemplary embodiment, the therapeutic agent may be
administered in a single fast bolus.
[0193] The rate of administration of the therapeutic agent may be
dependent on the ambient temperature. At room temperature, i.e.,
about 72.degree. F., the accuracy of the administration time may
range between about three percent and about ten percent.
[0194] Exemplary dimensions of exemplary devices are described with
reference to Tables 1-6. However, one of ordinary skill in the art
will recognize that the exemplary dimensions are provided for
illustrative purposes, and that exemplary automatic injection
devices are not limited to the illustrative dimensions.
[0195] In an exemplary embodiment, a wearable automatic injection
device may have an exemplary length of about 4.37 inches, an
exemplary width of about 2.12 inches, and an exemplary height of
about 1.25 inches. In an exemplary embodiment, the diameter of the
barrel portion is about 1.470 inches and the length of the barrel
portion is about 2.520 inches. Tables 1-3 summarize the components
of the length, width and height, respectively, for two exemplary
types of the exemplary device.
TABLE-US-00001 TABLE 1 Summary of components of the length of an
exemplary device (inch) Element Type 1 Type 2 Wall thickness 0.185
0.120 Septum 0.397 0.272 Needle 0.500 0.500 Barrel portion 2.520
2.520 Advance spring 0.470 0.322 Hydraulic connection 0.113 0.113
Wall thickness 0.185 0.120 Total 4.370 3.968
TABLE-US-00002 TABLE 2 Summary of components of the width of an
exemplary device (inch) Element Type 1 Type 2 Wall thickness 0.185
0.120 Administration interface lock 1.045 0.935 Barrel portion
width 0.470 0.470 Syringe lock 0.235 0.235 Wall thickness 0.185
0.120 Total 2.120 1.880
TABLE-US-00003 TABLE 3 Summary of components of the height of an
exemplary device (inch) Element Type 1 Type 2 Wall thickness 0.100
0.120 Needle cover 0.431 0.431 Septum 0.400 0.350 Spring solid
height 0.200 0.000 Wall thickness 0.185 0.125 Total 1.316 1.026
[0196] In an exemplary embodiment, the diameter of the barrel
portion in production may be increased from about 1.470 inches by
about 0.125 inches, and the length of the barrel portion may be
decreased in production from about 2.520 inches by about 0.732
inches. Tables 4-6 summarize the components of the length, width
and height, respectively, for two exemplary types of the exemplary
device.
TABLE-US-00004 TABLE 4 Summary of components of the length of an
exemplary device (inch) Element Type 1 Type 2 Wall thickness 0.185
0.120 Septum 0.397 0.272 Needle 0.500 0.250 Barrel portion 2.520
1.788 Advance spring 0.470 0.322 Hydraulic connection 0.113 0.113
Wall thickness 0.185 0.120 Total 4.370 2.986
TABLE-US-00005 TABLE 5 Summary of components of the width of an
exemplary device (inch) Element Type 1 Type 2 Wall thickness 0.185
0.120 Administration interface lock 1.045 0.935 Barrel portion
width 0.470 0.595 Syringe lock 0.235 0.235 Wall thickness 0.185
0.120 Total 2.120 2.005
TABLE-US-00006 TABLE 6 Summary of components of the height of an
exemplary device (inch) Element Type 1 Type 2 Wall thickness 0.100
0.120 Needle cover 0.431 0.493 Septum 0.400 0.350 Spring solid
height 0.200 0.000 Wall thickness 0.185 0.125 Total 1.316 1.088
[0197] FIG. 3 is a flow chart of an exemplary method 300 of
assembling an exemplary automatic injection device 100.
[0198] In step 302, a syringe assembly or a cartridge assembly may
be sterilized and assembled.
[0199] In step 304, an administration interface button may be
sterilized and assembled. In an exemplary embodiment in which the
therapeutic agent is contained in a cartridge assembly, the
administration interface button may include and/or hold an
administration interface, a piercing needle and a fluid pathway
provided between the piercing needle and the administration
interface. In this exemplary embodiment, the administration
interface, the piercing needle and the fluid pathway of the
administration interface button may be sterilized before assembly.
In an exemplary embodiment, a sterile piercing needle cover, e.g.,
a foil, a soft or rigid needle cover, etc., may be used to cover
the piercing needle and maintain the piercing needle in a sterile
condition. In an exemplary embodiment, a sterile cover, e.g., a
foil, a soft or rigid needle cover, etc., may be used to cover the
administration interface and maintain the administration interface
in a sterile condition. The sterile piercing needle, the sterile
piercing needle cover, the sterile administration interface and the
sterile administration interface cover may provide sterility
barriers to maintain sterility of the fluid pathway within the
administration interface button during and after assembly of the
automatic injection device. Thus, the inner surfaces and fluid
pathway within the administration interface button may be
maintained in a sterile condition during and after assembly of the
automatic injection device so that a sterile therapeutic agent may
be administered in a sterile manner
[0200] In another exemplary embodiment in which the therapeutic
agent is contained in a syringe assembly, the administration
interface button may include and/or hold an administration
interface and a fluid pathway for coupling the syringe assembly to
the administration interface. In this exemplary embodiment, the
administration interface and the fluid pathway of the
administration interface button may be sterilized before assembly.
In an exemplary embodiment, a sterile cover, e.g., a foil, a soft
or rigid needle cover, etc., may be used to cover the
administration interface and maintain the administration interface
in a sterile condition. In an exemplary embodiment, the
administration interface may also include a sterile septum covered
by a sterile septum cover for covering and maintaining sterility of
the septum. The sterile administration interface, the sterile
administration interface cover, the sterile septum and the sterile
septum cover may provide sterility barriers to maintain sterility
of the fluid pathway within the administration interface button
during and after assembly of the automatic injection device. Thus,
the inner surfaces and fluid pathway within the administration
interface button may be maintained in a sterile condition during
and after assembly of the automatic injection device so that a
sterile therapeutic agent may be administered in a sterile
manner.
[0201] In step 306, the sterile barrel portion of the syringe
assembly or the cartridge assembly may be filled with a sterile
dose of a therapeutic agent that is to be administered to a
patient. In step 308, a sterile bung may be placed at a proximal
portion (farther from the administration interface) within the
barrel portion of the syringe or cartridge assembly to seal the
dose of the therapeutic agent within the barrel portion.
[0202] In an exemplary embodiment in which the therapeutic agent is
contained in a cartridge assembly, a sterile septum covered by a
sterile septum cover may be provided at a distal portion (closer to
the administration interface) of the barrel portion of the
cartridge assembly. The sterile bung and the sterile septum may
collectively seal the sterile dose of the therapeutic agent inside
the sterile barrel portion. The sterile barrel portion, the sterile
bung, the sterile septum and the sterile septum cover may provide
sterility barriers to maintain sterility of the fluid pathway
within the cartridge assembly during and after assembly of the
automatic injection device. Thus, the containment of the
therapeutic agent within the sterile barrel portion by the sterile
bung and the sterile septum covered by the sterile septum cover
maintains sterility of the therapeutic agent during and after
assembly of the automatic injection device.
[0203] In another exemplary embodiment in which the therapeutic
agent is contained in a syringe assembly, a sterile piercing needle
may be attached to a distal portion of the barrel portion of the
syringe assembly. In an exemplary embodiment, a sterile piercing
needle cover, e.g., a foil, a soft or rigid needle cover, etc., may
be used to cover the piercing needle and maintain the piercing
needle in a sterile condition. The piercing needle cover may also
maintain sterility of the fluid conduit formed by and coupled to
the piercing needle. The sterile barrel portion, the sterile bung,
the sterile piercing needle and the sterile piercing needle cover
may provide sterility barriers to maintain sterility of the fluid
pathway within the syringe assembly. Thus, the containment of the
therapeutic agent within the sterile barrel portion by the sterile
bung and the sterile piercing needle covered by the sterile
piercing needle cover maintains sterility of the therapeutic agent
during and after assembly of the automatic injection device.
[0204] Using the exemplary embodiments described above, sterility
is maintained in a fluid pathway within and extending between the
barrel portion of the syringe or cartridge assembly and the
administration interface button. Sterility is maintained during and
after assembly of the automatic injection device so that the device
may be used to perform a sterile administration of a therapeutic
agent. In this manner, exemplary embodiments ensure that, during
administration of a sterile therapeutic agent, the therapeutic
agent takes or follows a sterile fluid pathway from the syringe or
cartridge assembly through the administration interface button to
the patient.
[0205] In an exemplary embodiment, the remaining components of the
wearable automatic injection device may be assembled in a
non-sterile environment, while maintaining sterility of the fluid
pathway within the device. In another exemplary embodiment, the
remaining components may be sterilized before assembly.
[0206] In step 310, a non-sterile plunger actuator, for example, a
biasing mechanism, may be inserted behind the bung for actuating
the bung in an administration state to eject the therapeutic agent
from the barrel portion.
[0207] In step 312, the syringe or cartridge assembly may be
inserted into a non-sterile housing. The housing may be
pre-assembled with one or more other non-sterile components, for
example, an adhesive layer, a protective film, a skin sensor foot,
and the like.
[0208] In step 314, the administration interface button (with an
enclosed sterile fluid pathway and a sterile administration
interface in an exemplary embodiment) may be inserted into the
non-sterile housing.
[0209] In step 316, the assembled automatic injection device may be
placed in an outer packaging, if necessary, and may then be
commercially packaged for sale. In an exemplary embodiment, a
portion of the device may be attached to a portion of the inner
surface of the packaging.
[0210] FIG. 4 is a flow chart of an exemplary method 400 of using
an exemplary automatic injection device. The wearable automatic
injection device packaged and pre-filled with a therapeutic agent
may be generally stored in refrigerated storage before use.
[0211] In step 402, the packaged automatic injection device may be
removed from storage. In step 404, the wearable automatic injection
device may be removed from its packaging and any over-wrap, and
warmed to room temperature, for example, by leaving the wearable
device outside the packaging at room temperature or by warming the
wearable device. In step 406, the patient may confirm that the
barrel portion contains a volume of the therapeutic agent through
an therapeutic agent inspection window disposed in the device
housing, and may also confirm the clarity of the therapeutic agent
if necessary.
[0212] In step 408, the administration site on the body of the
patient may be selected and prepared for the administration of the
therapeutic agent. In step 410, the patient uses the wearable
automatic injection device to administer the therapeutic agent to
the patient at the administration site. The steps generally
involved within step 410 are described below in connection with
FIG. 5. In step 412, after administering the therapeutic agent, the
wearable automatic injection device may be removed from the patient
and discarded in an appropriate manner
[0213] FIG. 5 is a flow chart of an exemplary method 500 of using
an exemplary automatic injection device to administer a
therapeutically effective amount of a therapeutic agent to a
patient. Exemplary method 500 is a detailed outline of step 410 in
FIG. 4.
[0214] In step 502, the patient removes the protective film that
covers and protects the adhesive layer of the wearable automatic
injection device. In an exemplary embodiment, a portion of the
protective film may be attached to the inner surface of the
packaging of the device, and removal of the device from the
packaging may automatically remove the protective film. In some
exemplary embodiments, removal of the protective film also removes
the administration interface cover, the piercing needle cover and
the septum cover in the syringe or cartridge stopper.
[0215] In step 504, the patient applies the patient contact portion
of the wearable automatic injection device with the adhesive layer
to the administration site on the patient's body (or an article of
clothing around the administration site) so that the device is
reliably retained on the administration site during the
administration of the therapeutically effective dose of therapeutic
agent.
[0216] In step 506, once the wearable automatic injection device is
attached to the administration site, the patient may depress the
administration interface button from a vertically raised position
in the pre-administration state to a vertically lowered position in
the administration state within the housing. In the vertically
raised position, the end of the administration interface button
bearing the administration interface is retracted within the
housing and is not exposed to the outside of the housing. When
depressed, the end of the administration interface button bearing
the administration interface is moved downward either linearly or
rotationally within the housing so that the administration
interface emerges from an aperture in the housing and is exposed
outside the housing. This allows the administration interface to
interface with the patient's body, e.g., by penetrating the
patient's body to an appropriate depth, for administration of the
therapeutic agent. The downward movement of the administration
interface button in the housing may be linear (i.e., a vertical
downward movement) or rotary (i.e., in a circular movement about a
pivot point).
[0217] In an exemplary embodiment, the administration interface
button is depressed into the housing by the patient manually
pushing down the administration interface button. In another
exemplary embodiment, the patient may activate an administration
trigger, for example, a trigger button located in a conveniently
accessible location such as the top of the housing, which causes
the administration trigger to automatically depress the
administration interface button into the housing and in turn, cause
the administration interface to interface with the patient's body,
e.g., by piercing the body of the patient. In an exemplary
embodiment, pressing the trigger button may release a latch in the
administration trigger that allows a spring to bias the
administration interface button downwardly in the housing. The same
motion of the administration interface button may cause the
administration interface to be inserted into or applied to the
administration site on the patient's body to an appropriate
depth.
[0218] In step 508, depressing the administration interface button
may trigger a syringe or cartridge actuator that moves the syringe
or cartridge assembly, more specifically, the barrel portion,
forwardly within and relative to the housing from a retracted
position (in which the distal end of the syringe or cartridge
assembly is spaced from the administration interface button) to an
extended position (in which the distal end of the syringe or
cartridge assembly is adjacent to and/or in contact with the
administration interface button). In another exemplary embodiment,
the syringe or cartridge actuator is triggered not by depressing
the administration interface button, but by the patient activating
a trigger, for example, in the form of a trigger button. In an
exemplary embodiment, movement of the syringe or cartridge assembly
toward the administration interface button may cause the piercing
needle to pierce the septum.
[0219] In step 510, the plunger actuator may break the static
friction (i.e., stiction) between the bung and the inside wall or
walls of the barrel portion and cause the bung to move forwardly
toward the piercing needle in the administration interface button
to administer the therapeutic agent via the administration
interface. The plunger actuator may overcome the bung stiction in
one step and actuate the bung in a subsequent step, or the plunger
actuator may overcome the bung stiction and actuate the bung
concurrently. Movement of the bung may cause the dose to be
released through the piercing needle into the administration
interface, and the dose may thereby be administered to the
patient.
[0220] In an exemplary embodiment, the forward advancement of the
syringe or cartridge assembly within the housing and the forward
advancement of the bung within the barrel portion may take place in
separate steps. In another exemplary embodiment, the forward
advancement of the syringe or cartridge assembly within the housing
and the forward advancement of the bung within the barrel portion
may take place in the same step, for example, simultaneously.
[0221] The rate of therapeutic agent administration may depend on
the characteristics of the plunger actuator. The plunger actuator
may take the form of several exemplary embodiments. In some
exemplary embodiments, the plunger actuator may employ means of
energy storage and release, for example, biasing mechanisms
(including, but not limited to, one or more springs, for example,
spiral springs or helical compression springs), compressed gases,
chemical gas generators (such as expanding foams), osmotic
pressure, hydrogel expansion, and the like. A damping or control
mechanism (including, but not limited to, a viscous damper or an
escapement) may be used to absorb energy, for example, an initial
release of energy, and to provide a more controlled release of
energy during energy release by the plunger actuator. A flow
restrictor placed in a fluid pathway between the administration
interface and the bung may be used to further regulate the rate of
therapeutic agent administration, for example, where the plunger
actuator administers an unconstrained spring force via a working
fluid. Thus, an appropriate plunger actuator and an appropriate
control mechanism may be selected to administer the dose at a
controlled rate, for example, in a single fast bolus, free of or
substantially free of any burning sensation to the patient.
[0222] In an exemplary embodiment, depressing the administration
interface button may arm the retraction mechanism which, when
triggered, retracts the administration interface button into the
housing 102 after administration in a post-administration
state.
[0223] In step 512, upon administration of the therapeutically
effective dose, the bung and/or the plunger actuator may activate
the end-of-dose retraction trigger of the retraction mechanism. The
bung and/or the plunger actuator may include a linking member
connected to the end-of-dose retraction trigger. The linking member
may include a tether, a tab or other linkage mechanism. The linking
member may be of a suitable length such that, when the bung has
been moved to the end of the syringe or cartridge assembly (in
order to administer a dose of the therapeutic agent), the linking
member triggers a latch that in turn activates the retraction
trigger.
[0224] In step 514, once the end-of-dose retraction trigger is
activated, the retraction mechanism may retract the administration
interface button upward inside the housing and away from the
patient contact portion so that the syringe or cartridge assembly
enters a post-administration state. In an exemplary embodiment, the
movement of the administration interface button from the
administration state to the post-administration state creates an
audible sound, for example, a "click," which provides an aural
indication of the completion of therapeutic agent administration.
Once retracted, the administration interface button protrudes
outside the housing, which provides a visual indication of the
state of the wearable automatic injection device, for example,
completion of therapeutic agent administration or a visual
indication of the device in the post-administration state.
[0225] However, if the wearable device is removed from the body of
the patient before the completion of therapeutically effective dose
of the therapeutic agent, the skin sensor foot may extend to the
outside of the housing and activate the early-removal retraction
trigger of the retraction mechanism. Once the early-removal
retraction trigger is activated, the retraction mechanism deploys
the administration interface button upward in the housing away from
the patient contact portion so that the syringe or cartridge
assembly enters a post-administration state. In an exemplary
embodiment, the plunger actuator may continue to move forwardly in
the barrel portion toward the piercing needle when the device is
removed from the patient before completion of administration of a
therapeutically effective dose of the therapeutic agent.
[0226] In step 516, upon retraction, an administration interface
locking mechanism engages with the administration interface to
prevent redeployment of the administration interface after
administration of the therapeutic agent in order to provide
needle-stick protection. The administration interface lock may be a
member that prevents the administration interface from protruding
outside the housing once engaged, and may be located in the housing
near the administration interface. Exemplary administration
interface locks may include, but are not limited to, a plastic
plate, a metal plate, a clip, and the like.
[0227] FIGS. 6A-6C illustrate an exemplary embodiment of a wearable
automatic injection device 600 suitable for linear insertion or
application of an administration interface to a patient. By linear
insertion, the end of a cartridge assembly bearing an
administration interface descends linearly within a housing of the
wearable automatic injection device so that the administration
interface is inserted into or applied to the patient. More
specifically, FIG. 6A illustrates the exemplary wearable device in
a pre-administration state, for example, as packaged; FIG. 6B
illustrates the exemplary wearable device in an administration
state just before, while or just after it administers a therapeutic
agent to a patient; and FIG. 6C illustrates the exemplary wearable
device in a post-administration state after it has completed
administration of the therapeutic agent to the patient or removed
from the patient prior to completion of administration of the
therapeutic agent. In some of FIGS. 6A-6C, the administration
interface is represented as a single injection needle. However,
exemplary administration interfaces are not limited to the
illustrative embodiments shown in FIGS. 6A-6C.
[0228] The wearable automatic injection device 600 includes a
housing 635 for housing a therapeutic agent cartridge assembly 610
which contains a dose of a therapeutic agent for administering to a
patient. In an exemplary embodiment, the outside of the therapeutic
agent cartridge assembly 610 may be provided with one or more
ridges, and the inside of the housing 635 may be provided with one
or more grooves or channels that provide a smooth pathway for the
ridges of the cartridge assembly 610 as the cartridge assembly
moves within the housing 635. The one or more ridges on the outside
of the cartridge assembly 610 may take the form of raised lines on
the cartridge assembly 610. The one or more grooves or channels on
the inside of the housing 635 may take the formed of U-shaped
depressed or trough-like lines. The top portion of the grooves or
channels may be open so that the ridges may slide in and out of the
top portion of the grooves or channels. In the linear insertion
embodiment illustrated in FIGS. 6A-6C, the ridges and
grooves/channels may be straight lines. In the rotary insertion
embodiment illustrated in FIGS. 7A-7C, the ridges and
grooves/channels may be lines that are curved about the center of
rotation, i.e., the pivot point of the cartridge assembly 610.
[0229] In another exemplary embodiment, the outside of the
cartridge assembly 610 may not have any ridges, and the inside of
the housing 635 may not have any grooves or channels.
[0230] The housing 635 preferably has an elongated configuration,
though one of ordinary skill in the art will recognize that the
housing 635 may have any suitable size, shape and configuration for
housing a barrel portion for holding a dose of a therapeutic agent
and couplable to an administration interface for administering the
therapeutic agent to a patient. The housing 635 may be formed of
any suitable material including, but not limited to, plastic and
other known materials. In another embodiment, the therapeutic agent
cartridge 610 may be formed of any compatible material suitable for
sterilization including, but not limited to, glass and other known
materials.
[0231] The housing 635 includes an adhesive layer 640 disposed
along a patient contact portion of the housing 635 that is placed
proximal to the skin of the patient or an article of clothing of
the patient. In some embodiments, the adhesive layer 640 is
configured to be placed on the skin of the patient to attach the
housing 635 to the patient to administer a therapeutic agent. The
adhesive layer 640 includes a non-adhesive removal mechanism 645,
e.g., a tab, which is not adhesive. The non-adhesive removal
mechanism 645 may be gripped by the patient and pulled to remove
the adhesive layer 640 and thus the wearable automatic injection
device 600 from the skin or clothing of the patient.
[0232] Before the wearable automatic injection device 600 is put to
use, for example, in the pre-administration state, the adhesive
layer 640 is covered by a protective film 650 which preserves the
adhesive nature of the adhesive layer 640. The protective film 650
may include a removal mechanism 655, e.g., a tab, which may be
gripped by the patient and pulled to remove the protective film 650
from the adhesive layer 640. This exposes the adhesive layer 640,
allowing the patient to attach the housing 635 to his or her skin
or an article of clothing by placing the side with the adhesive
layer 640 on the skin or the article of clothing.
[0233] In exemplary embodiments, the protective film 650 (in FIG.
6A)/750 (in FIG. 7A) may include a linking member that is connected
to the plunger actuator 630 (in FIG. 6A)/730 (in FIG. 7A). The
linking member may include a tether, a tab or other linkage
mechanism. When the protective film 650 (in FIG. 6A)/750 (in FIG.
7A) is removed, the linking member of the protective film 650 (in
FIG. 6A)/750 (in FIG. 7A) relieves static friction between the bung
615 (in FIG. 6A)/715 (in FIG. 7A) and the interior wall of the
barrel 605 (in FIG. 6A)/705 (in FIG. 7A), and triggers the plunger
actuator 630 (in FIG. 6A)/730 (in FIG. 7A).
[0234] The therapeutic agent cartridge assembly 610 may include a
hollow barrel portion 605 for holding a therapeutically effective
dose of the therapeutic agent to be administered to a patient. The
illustrative barrel portion 605 is substantially cylindrical in
shape, although one of ordinary skill in the art will recognize
that the barrel portion 605 may have any suitable shape or
configuration. A bung 615 seals the dose of the therapeutic agent
within the barrel portion 605. The therapeutic agent cartridge
assembly 610 may also include an administration interface 625
couplable or coupled to, and in fluid communication with, the
barrel portion 605, through which the dose can be ejected by
applying pressure to the bung 615.
[0235] In some exemplary embodiments, the administration interface
625 may include one or more injection needles having any suitable
size, shape and configuration suitable for piercing the skin of the
patient to administer the therapeutic agent, and is not limited to
the illustrative embodiment. In an exemplary embodiment, the
administration interface 625 may include a single injection needle
(shown as a continuous line in FIGS. 6A-6C). In another exemplary
embodiment, the administration interface 625 may include two or
more injection needles (the additional needles shown as dashed
lines in FIGS. 6A-6C). In some other exemplary embodiments, the
administration interface 625 may include a needle-free pad and/or a
needle-free patch for performing a topical administration of a
therapeutic agent.
[0236] Suitable needles that may be used in exemplary
administration interfaces may have a length configured or selected
to provide an administration depth suitable for the desired
therapy. Subcutaneous injections typically penetrate about six to
ten millimeters into the skin. In an exemplary embodiment,
exemplary injection needles may have a length of about twelve mm
and may be administered to a depth of about seven mm into the skin.
In other exemplary embodiments, exemplary injection needles may
have lengths suitable for intradermal, other subcutaneous, or
intramuscular therapies. Suitable needles may have a wall thickness
suitable to provide sufficient mechanism strength, a diameter
suitable to allow a desired flow rate of the substance while
minimizing patient sensation, and a tip geometry suitable for the
desired therapy while minimizing patient sensation.
[0237] Exemplary injection needles may be coated as needed to
minimize patient sensation as allowed by therapy. The
administration interface 625 may be covered and maintained in a
septic condition by an administration interface cover 620, for
example, a soft needle shield, a rigid needle shield or both.
[0238] In the exemplary embodiment illustrated in FIGS. 6A-6C, the
administration interface 625 projects substantially at a right
angle to the longitudinal axis of the wearable device 600. In this
exemplary embodiment, the barrel portion 605 includes an elbow 607
that extends substantially at a right angle to the longitudinal
axis of the device 600. In this embodiment, the administration
interface 625 is connected to the elbow 607.
[0239] The wearable automatic injection device 600 may include a
plunger actuator 630 for selectively actuating the bung 615
forwardly toward the distal end of the therapeutic agent cartridge
assembly 610 to administer the therapeutically effective dose
contained in the barrel portion 605 to the patient. The plunger
actuator 630 may employ an energy storage and controlled energy
release mechanism to actuate the bung 615. In an exemplary
embodiment, the plunger actuator 630 may include a biasing
mechanism, for example, a spring, that is retracted before
administration and that is released during administration to
actuate the bung 615 forwardly in the barrel portion 605. In
another exemplary embodiment, the plunger actuator 630 may include
a chemical gas generator, for example, an expanding foam, that is
in a non-expanded phase before administration and that expands
during administration to actuate the bung 615 forwardly in the
barrel portion 605 toward the distal end of the therapeutic agent
cartridge assembly 610. In other exemplary embodiments, the plunger
actuator 630 may employ compressed gases, osmotic pressure,
hydrogel expansion, and the like. A damping mechanism may be used
to absorb energy, for example, an initial release of energy, and to
provide a controlled release of energy during energy release by the
plunger actuator 630 (in FIG. 6A)/730 (in FIG. 7A). A flow
restrictor placed in a fluid pathway between the administration
interface and the bung 615 (in FIG. 6A)/715 (in FIG. 7A) may be
used to further regulate the rate of therapeutic agent
administration, for example, where the plunger actuator 630 (in
FIG. 6A)/730 (in FIG. 7A) administers an unconstrained spring
force.
[0240] In an exemplary embodiment, the plunger actuator 630 may be
advanced forwardly inside the barrel portion 605 in a constant
linear motion. Any number of mechanisms, internal or external to
the wearable automatic injection device 600, may be used to provide
a constant linear motion including, but not limited to, a stepper
motor connected to a gear drive system.
[0241] The bung 615 (in FIG. 6A)/715 (in FIG. 7A) and/or the
plunger actuator 630 (in FIG. 6A)/730 (in FIG. 7A) may include a
linking member connected to the retraction trigger. The linking
member may include a tether, a tab or other linkage mechanism. The
linking member may be of a suitable length such that, when the bung
615 (in FIG. 6A)/715 (in FIG. 7A) has been moved to the end of the
cartridge assembly 610 (in FIG. 6A)/710 (in FIG. 7A) (in order to
administer a dose of the therapeutic agent), the linking member
triggers a latch that in turn activates the retraction trigger.
[0242] Referring now to FIG. 6C, in an exemplary embodiment, the
housing 635 includes a skin sensor foot 660, which is a structure
housed under or in the portion of the housing 635 proximal to the
administration site. Prior to administration of the therapeutic
agent and during administration, the skin sensor foot 660 is
retained within or forms a portion of the underside of the housing
635. When the wearable automatic injection device 600 is attached
to the administration site and activated, the skin sensor foot 660
may be free to move but may be constrained by the administration
site. When the wearable automatic injection device 600 is removed
from the administration site, regardless of whether administration
of the therapeutic agent was completed, the skin sensor foot 660 is
no longer constrained, and extends and projects outside the
periphery of the housing 635. This, in turn, activates the removal
retraction trigger.
[0243] FIG. 6A illustrates the wearable automatic injection device
600 in a pre-administration state, for example, as packaged and
ready for use or as ready for packaging. The device 600 may include
a pre-fillable and/or pre-filled syringe or cartridge assembly. In
an exemplary embodiment, in a pre-administration state, the syringe
or cartridge assembly may be in a retracted position ready for use.
In the pre-administration state, the therapeutic agent cartridge
assembly 610 is partially disposed within the housing 635 at an
elevated location distal from the administration site, and the
administration interface 625 is retracted within the housing 635.
Visual indications to the patient that the wearable automatic
injection device 600 is not in operation may include a portion of
the therapeutic agent cartridge assembly 610 projecting outside the
housing 635 in the pre-administration state. The barrel portion 605
contains a dose of a therapeutic agent which is contained by the
interior space defined between the wall or walls of the barrel
portion 605 and the bung 615. In an embodiment, the plunger
actuator 630 stores energy.
[0244] FIG. 6B illustrates the wearable automatic injection device
600 in an administration state ready to administer, in the process
of administering or just after administering a therapeutically
effective dose of a therapeutic agent, in which the therapeutic
agent cartridge assembly 610 is in a depressed position. In the
depressed position, the therapeutic agent cartridge assembly 610 is
disposed within the housing 635 at a depressed location proximal to
the administration site, and the administration interface 625
projects outside the housing 635 through an aperture in the housing
635 so that it can penetrate the body at the administration site.
In the administration state, the therapeutic agent cartridge
assembly 610 does not project outside the housing 635 to provide a
visual indication to the patient that the wearable automatic
injection device 600 is in operation. The plunger actuator 630
releases its stored energy to actuate the bung 615. This
cooperative movement of the plunger actuator 630 and the bung 615
ejects the therapeutic agent in the barrel portion 605 out through
the administration interface 625.
[0245] FIG. 6C illustrates the wearable automatic injection device
600 in a post-administration state, for example, after
administering a therapeutically effective dose of the therapeutic
agent or removal of the wearable automatic injection device 600
from the patient before administration of a therapeutically
effective dose of the therapeutic agent, in which the therapeutic
agent cartridge assembly 610 is in a retracted position. In the
retracted position, the therapeutic agent cartridge assembly 610 is
disposed within the housing 635 at an elevated location distal from
the administration site, and the administration interface 625 is
retracted within the housing 635. A portion of the therapeutic
agent cartridge assembly 610 projects outside the housing 635 to
provide a visual indication to the patient that the wearable
automatic injection device assembly 600 is not in operation (i.e.,
in a post-administration state). The barrel portion 605 may be
empty of the therapeutic agent, and the plunger actuator 630 may no
longer store energy.
[0246] The housing 635 includes a retraction mechanism that
automatically raises the therapeutic agent cartridge assembly 610
from the administration state (depressed position shown in FIG. 6B)
to the post-administration state (retracted position shown in FIG.
6C). In an exemplary embodiment, the retraction mechanism may
include a biasing mechanism, for example, a spring, that biases the
cartridge assembly away from the administration site when the
retraction mechanism is triggered.
[0247] The retraction mechanism includes an end-of-dose retraction
trigger that, when activated, triggers the retraction mechanism.
The end-of-dose retraction trigger is activated when the
therapeutically effective dose of therapeutic agent in the wearable
automatic injection device is administered. In an exemplary
embodiment, the end-of-dose retraction trigger may include a latch,
for example, a flexible plastic hook, that is released upon
completed administration of the therapeutic agent. The retraction
mechanism also includes an early-removal retraction trigger that,
when activated, triggers the retraction mechanism. The
early-removal retraction trigger is activated when the wearable
automatic injection device is removed from the administration site
before the therapeutically effective dose of therapeutic agent is
completely administered.
[0248] In an exemplary embodiment, the early-removal retraction
trigger may include a latch, for example, a flexible plastic hook,
that is released upon removal of the wearable automatic injection
device 600 from the administration site. The retraction mechanism
is responsive to the end-of-dose retraction trigger and responsive
to the early-removal retraction trigger to automatically retract
the cartridge assembly from the administration site.
[0249] FIGS. 7A-7C illustrate an exemplary embodiment of a wearable
automatic injection device 700 suitable for rotary insertion or
application of the administration interface to a patient. In rotary
insertion, the end of a therapeutic agent cartridge assembly 710
bearing an administration interfaces 725 descends in a rotary
fashion about a pivot point to insert or apply the administration
interface 725 to the patient. The administration interface 725 may
be configured to administer a therapeutic agent on, in or through
the skin to any desired depth. More specifically, FIG. 7A
illustrates the exemplary wearable device in a pre-administration
state, for example, as packaged with a pre-filled and curved
administration interface and barrel portion holding a therapeutic
agent; FIG. 7B illustrates the exemplary wearable device while in
an administration state just before, while or just after
administering a therapeutic agent to a patient; and FIG. 7C
illustrates the exemplary wearable device in a post-administration
state after administration of the therapeutic agent to the patient
or removal of the wearable device from the patient prior to
completing administration of the therapeutic agent to the patient.
In some of FIGS. 7A-7C, the administration interface is represented
as a single injection needle. However, exemplary administration
interfaces are not limited to the illustrative embodiments shown in
FIGS. 7A-7C.
[0250] The therapeutic agent cartridge assembly 710 is rotatably
movable within the housing 735 about a pivot point 765 in the
housing. In an exemplary embodiment, the outside of the therapeutic
agent cartridge assembly 710 may be provided with one or more
ridges, and the inside of the housing 735 may be provided with one
or more grooves or channels that provide a pathway for the ridges
of the cartridge 710 as the cartridge moves within the housing 735
amongst the various states. In another exemplary embodiment, the
outside of the cartridge assembly 710 is free of ridges, and the
inside of the housing 735 is free of grooves or channels.
[0251] When the therapeutic agent cartridge assembly 710 is
depressed into the housing 735, the therapeutic agent cartridge
assembly 710 moves rotatably downward about the pivot point 765
such that the administration interface 725 becomes exposed and
penetrates the skin of the patient. In an exemplary embodiment, the
administration interface 725 may include a single injection needle
(shown as a continuous line in FIGS. 7A-7C). In another exemplary
embodiment, the administration interface 725 may include two or
more injection needles (the additional needles shown as dashed
lines in FIGS. 7A-7C). In some other exemplary embodiments, the
administration interface 725 may include a needle-free pad and/or a
needle-free patch for performing a topical administration of a
therapeutic agent.
[0252] In the exemplary embodiment illustrated in FIGS. 7A-7C, the
administration interface 725 penetrates the skin of the patient at
an angle offset from 90.degree.. Similarly, when the therapeutic
agent cartridge assembly 710 is retracted, the therapeutic agent
cartridge assembly 710 moves rotatably upward about the pivot point
765 such that the administration interface 725 retracts within the
housing 735. The mechanism to implement this rotational motion of
the therapeutic agent cartridge assembly 710 may be simpler and
more robust than the mechanism required for the linear insertion of
FIGS. 6A-6C.
[0253] In an exemplary embodiment, the administration interface 725
is curved, with a radius defined by the pivot point 765 and the
distance from the administration interface 725 to the pivot point
765 along the longitudinal axis of the housing 735. The curvature
of the administration interface 725 increases the comfort of the
patient during application of the administration interface. For
example, in an exemplary embodiment, the curvature of the
administration interface 725 increases comfort of the patient
during insertion of one or more injection needles of an exemplary
administration interface into the patient's body. In an exemplary
embodiment in which the administration interface 725 includes one
or more injection needles, the administration interface 725 may be
preferentially oriented with the sharp needle tip closest to the
pivot point 765.
[0254] Features in FIGS. 7A-7C similar to those illustrated in
FIGS. 6A-6C are described above in connection with FIGS. 6A-6C.
[0255] In exemplary embodiments, the therapeutic agent cartridge
assembly 610 and 720 of FIGS. 6A-6C and 7A-7C, respectively, may be
pre-filled with any volume of a therapeutic agent, for example, a
therapeutic antibody. In an exemplary embodiment, the cartridge
assembly 610 and 720 may be pre-filled with a volume of about 0.1
to about 3.0 milliliters, although exemplary cartridge assemblies
are not limited to these exemplary volumes. In another exemplary
embodiment, the cartridge assembly 610 and 720 may be pre-filled
with a volume of up to about 1 milliliter.
[0256] In exemplary embodiments, the wearable automatic injection
device 600 (in FIG. 6A)/700 (in FIG. 7A) may be used to administer
the therapeutically effective amount of therapeutic agent over a
period of time ranging from about twenty seconds to about twelve
hours. In an exemplary embodiment, the therapeutic agent may be
administered at a fixed rate for an administration time of between
about five minutes and about thirty minutes. The wearable automatic
injection device 600 (in FIG. 6A)/700 (in FIG. 7A) may be used to
administer a volume of therapeutic agent in a single fast
bolus.
[0257] The rate of administration of the therapeutic agent may be
dependent on the ambient temperature. At room temperature, i.e.,
about 72.degree. F., the accuracy of the administration time may
range between about three percent and about ten percent.
[0258] FIG. 8 is a flow chart of an exemplary method 800 of
assembling an exemplary wearable automatic injection device 600 or
700.
[0259] In step 805, the barrel portion 605/705 of the cartridge
assembly, administration interface 625/725 and administration
interface cover 620/720 are sterilized. In step 810, the barrel
portion 605/705 is filled with a sterile dose of the therapeutic
agent that is to be administered to the patient. In step 815, a
sterile bung 615/715 is placed in the barrel portion 605/705 to
seal the therapeutic agent inside the barrel portion 605/705. The
containment of the therapeutic agent inside the wearable automatic
injection device 600 or 700 by the sterile barrel portion 605/705,
the sterile bung 615/715, the administration interface 625/725, and
the cover assembly 620/720 provide sterility barriers to maintain
sterility of a fluid pathway of the therapeutic during and after
assembly of the device.
[0260] In an exemplary embodiment, the remaining components of the
wearable automatic injection device may be assembled in a
non-sterile environment after the barrel portion 605/705 is
pre-filled with a therapeutic agent, while maintaining sterility of
the fluid pathway within the device. In another exemplary
embodiment, the remaining components of the wearable automatic
injection device may be assembled in a sterile environment.
[0261] In step 820, a non-sterile plunger actuator 630/730 is
inserted behind the bung 615/715 in the therapeutic agent cartridge
assembly 610/710 for actuating the bung in an administration state
to eject the therapeutic agent from the barrel portion.
[0262] In step 825, the therapeutic agent cartridge assembly
610/710 is inserted into a non-sterile housing 635/735. The housing
635/735 may be pre-assembled with one or more other non-sterile
components, for example, the adhesive layer 640/740, the protective
film 650/750, the skin sensor foot 660/760.
[0263] In step 830, the assembled wearable automatic injection
device 600/700 may be placed in an outer packaging, if necessary,
and is then commercially packaged for sale. In an exemplary
embodiment, a portion of the device may be attached to a portion of
the inner surface of the packaging.
[0264] FIG. 9 is a flow chart of an exemplary method 900 of using
an exemplary wearable automatic injection device 600 or 700. The
wearable automatic injection device 600/700 packaged and pre-filled
with a therapeutic agent is generally stored in refrigerated
storage before use. In step 905, the packaged wearable automatic
injection device 600/700 is removed from storage. In step 910, the
wearable automatic injection device 600/700 is removed from its
packaging and any over-wrap and warmed to room temperature, for
example, by leaving the wearable device outside the packaging at
room temperature or by warming the wearable device. In step 915,
the patient confirms the therapeutic agent cartridge assembly
610/710 includes a volume of the therapeutic agent in the wearable
device 600/700 through an therapeutic agent inspection window
disposed in the wearable device housing and may also confirm the
clarity of the therapeutic agent, if necessary. In step 920, the
administration site on the patient's body is selected and prepared
for the administration of the therapeutic agent. In step 925, the
patient uses the wearable automatic injection device 600/700 to
administer the therapeutic agent to the administration site on the
patient. The steps generally involved within step 920 are described
below in connection with FIG. 10. In step 930, after the wearable
automatic injection device 600/700 is removed from the patient, the
removed wearable automatic injection device 600/700 is discarded in
an appropriate manner.
[0265] FIG. 10 is a flow chart of an exemplary method 1000 of using
an exemplary wearable automatic injection device 600 or 700 to
administer a therapeutically effective amount of a therapeutic
agent to a patient. Exemplary method 1000 is a detailed outline of
step 920 in FIG. 9. In step 1005, the patient removes the
protective film 650/750 that covers and protects the adhesive layer
640/740 of the wearable automatic injection device 600/700. In an
exemplary embodiment, a portion of the protective film may be
attached to the inner surface of the packaging, and removal of the
device from the packaging may automatically remove the protective
film. In some exemplary embodiments, removal of the protective film
650/750 also removes the cover assembly 620/720 and exposes the
administration interface 625/725 for administering the therapeutic
agent to the patient. In some exemplary embodiments, removal of the
protective film 650/750 also breaks static friction (i.e.,
stiction) between the bung 615/715 and the interior wall of the
barrel 605/705 and triggers the plunger actuator 630/730. In
exemplary embodiments, the protective film 650/750 may include a
linking member that is connected to the plunger actuator 630/730.
The linking member may include a tether, a tab or other linkage
mechanism. When the protective film 650/750 is removed, the linking
member of the protective film 650/750 relieves static friction
between the bung 615/715 and the interior wall of the barrel
605/705, and triggers the plunger actuator 630/730.
[0266] In step 1010, the patient applies the patient contact
portion of the wearable automatic injection device 600/700 with the
adhesive layer 640/740 to the administration site (or an article of
clothing around the administration site) so that the wearable
device is reliably retained on the administration site during the
administration of the therapeutically effective dose of therapeutic
agent.
[0267] In step 1015, once the wearable automatic injection device
600/700 is attached to the administration site, the therapeutic
agent cartridge assembly 610/710 is depressed from a ready position
in the pre-administration state to a depressed position in the
administration state within the housing 635/735. In the ready
position, the end of the therapeutic agent cartridge assembly
610/710 bearing the administration interface 625/725 is retracted
within the housing 635/735 and is not exposed to the outside of the
housing. When depressed, the end of the therapeutic agent cartridge
assembly 610/710 bearing the administration interface 625/725 is
moved downward either linearly or rotationally within the housing
635/735 so that the administration interface 625/725 emerges from
an aperture in the housing 635/735 and is exposed. This allows the
administration interface 625/725 to penetrate the body of the
patient to an appropriate depth for administration of the
therapeutic agent. The downward movement of the therapeutic agent
cartridge assembly 610/710 in the housing 635/735 may be linear
(i.e., a vertical downward movement) or rotary (i.e., in a circular
movement about a pivot point). FIGS. 6B and 7B illustrate exemplary
embodiments of the wearable automatic injection device 600 and 700
in an administration state with the therapeutic agent cartridge
610/710 depressed into the housing 635/735 after step 1015 is
performed.
[0268] In an exemplary embodiment, the therapeutic agent cartridge
assembly 610/710 is depressed into the housing 635/735 by the
patient manually pushing down the therapeutic agent cartridge
assembly 610/710. In another exemplary embodiment, the patient may
activate an insertion trigger, for example, a trigger button
located in a conveniently accessible location such as the top of
the housing 635/735, which causes an insertion trigger to
automatically depress the therapeutic agent cartridge assembly
610/710 into the housing 635/735 and in turn, cause the
administration interface 625/725 to pierce the body of the patient.
In an exemplary embodiment, pressing the trigger button may release
a latch in the trigger that allows a spring to bias the cartridge
assembly 610/710 downwardly in the housing 635/735. The same motion
of the cartridge assembly 610/710 may cause the administration
interface 625/725 to be inserted into or applied to the
administration site on the patient to an appropriate depth.
[0269] In an exemplary embodiment, depressing the therapeutic agent
cartridge assembly 610/710 triggers the plunger actuator 630/730 to
begin movement of the bung 615/715 to cooperatively administer the
therapeutically effective dose to the patient. Depression of the
therapeutic agent cartridge assembly 610/710 causes the plunger
actuator 630/730 to break the static friction (i.e., stiction)
between the bung 615/715 and the inside wall or walls of the barrel
portion 605/705 and cause the bung 615/715 to move forwardly toward
the administration interface 625/725 in the therapeutic agent
cartridge assembly 610/710 to administer the therapeutic agent via
the administration interface 625/725. The plunger actuator 630/730
may overcome the bung stiction in one step and actuate the bung in
a subsequent step, or the plunger actuator 630/730 may overcome the
bung stiction and actuate the bung concurrently. In another
exemplary embodiment, the plunger actuator 630/730 is triggered not
by depressing the therapeutic agent cartridge, but by the patient
activating an administration trigger, for example, in the form of a
trigger button.
[0270] The rate of therapeutic agent administration may depend on
the characteristics of the plunger actuator 630/730. The plunger
actuator 630/730 may take the form of several exemplary
embodiments. In some exemplary embodiments, the plunger actuator
630/730 may employ means of energy storage and release, for
example, biasing mechanisms (such as springs), compressed gases,
chemical gas generators (such as expanding foams), osmotic
pressure, hydrogel expansion, and the like. A damping mechanism may
be used to absorb energy, for example, an initial release of
energy, and to provide a more controlled release of energy during
energy release by the plunger actuator 630/730. A flow restrictor
placed in a fluid pathway between the administration interface and
the bung 615/715 may be used to further regulate the rate of
therapeutic agent administration, for example, where the plunger
actuator 630/730 administers an unconstrained spring force. Thus,
an appropriate plunger actuator 630/730 and an appropriate flow
restrictor may be selected to administer the dose at a controlled
rate, for example, in a single fast bolus free, of or substantially
free of any burning sensation to the patient.
[0271] In an exemplary embodiment, depressing the therapeutic agent
cartridge assembly 610/710 also arms the retraction mechanism
which, when triggered, retracts the therapeutic agent cartridge
assembly 610/710 into the housing 635/735.
[0272] In step 1020, the therapeutic agent cartridge assembly
610/710 is retracted from the depressed position to a retracted
position in a post-administration state so that it protrudes
outside the housing 635/735 and the administration interface
625/725 is retracted within the housing 635/735 or protected by the
skin sensor foot 660/760 or both. FIGS. 6C and 7C illustrate
exemplary embodiments of automatic injection device 600 and 700,
respectively, in a retracted position after step 1020. Step 1020 is
performed either when the therapeutically effective dose of
therapeutic agent is administered or when the wearable automatic
injection device 600/700 is removed from the administration site
before the therapeutically effective dose is completely
administered.
[0273] Upon administration of the therapeutically effective dose,
the bung 615/715 and/or the plunger actuator 630/730 activates the
end-of-dose retraction trigger of the retraction mechanism. The
bung 615/715 and/or the plunger actuator 630/730 may include a
linking member connected to the retraction trigger. The linking
member may include a tether, a tab or other linkage mechanism. The
linking member may be of a suitable length such that, when the bung
615/715 has been moved to the end of the cartridge assembly 610/710
(in order to administer a dose of the therapeutic agent), the
linking member triggers a latch that in turn activates the
retraction trigger.
[0274] Once the end-of-dose retraction trigger is activated, the
retraction mechanism deploys the therapeutic agent cartridge
assembly 610/710 upward inside the housing 635/735 and away from
the patient contact portion so that the therapeutic agent cartridge
assembly 610/710 enters a post-administration state. In an
exemplary embodiment, the movement of the therapeutic agent
cartridge assembly 610/710 from the administration state to the
post-administration state creates an audible sound, for example, a
"click," which provides an aural indication of the completion of
therapeutic agent administration.
[0275] Once retracted, the therapeutic agent cartridge assembly
610/710 protrudes outside the housing 635/735 (as shown in FIGS. 6C
and 7C), which provides a visual indication of the state of the
wearable automatic injection device 600/700, for example,
completion of therapeutic agent administration or a visual
indication of the device in the post-administration state.
[0276] However, if the wearable device 600/700 is removed from the
body of the patient before the completion of therapeutically
effective dose of the therapeutic agent, the skin sensor foot
660/760 extends to the outside of the housing 635/735 and activates
the early-removal retraction trigger of the retraction mechanism.
Once the early-removal retraction trigger is activated, the
retraction mechanism deploys the therapeutic agent cartridge
assembly 610/710 upward in the housing 635/735 away from the
patient contact portion so that the therapeutic agent cartridge
assembly 610/710 is returned to a retracted position. In an
exemplary embodiment, the plunger actuator 630/730 may continue to
move forwardly in the therapeutic agent cartridge 610/720 toward
the administration interface 625/725 when the wearable device
600/700 is removed from the patient before completion of
administration of a therapeutically effective dose of the
therapeutic agent.
[0277] In step 1025, upon retraction, an automatic administration
interface lock engages with the administration interface 625/725 to
prevent its redeployment to provide needle-stick protection. The
administration interface lock may be a member that prevents the
administration interface 625/725 from exiting the housing 635/735
once engaged, and may be located in the housing 635/735 near the
administration interface 625/725. Exemplary administration
interface locks may include, but are not limited to, a plastic
plate, a metal plate, a clip, and the like.
[0278] FIGS. 11A and 11B illustrate an exemplary wearable automatic
injection device including a syringe and an exemplary transfer
mechanism. FIG. 11A illustrates a perspective view of the device.
FIG. 11B illustrates a disassembled view showing the components of
the device. The automatic injection device 1100 includes a housing
portion 1102 that includes an adhesive layer 1104 provided at a
patient contact portion that may be used to attach the device to a
patient's body or clothing.
[0279] The housing portion 1102 holds a syringe 1106 in a
stationary or moveable manner in the device 1100. The syringe 1106
holds a dose of a therapeutic agent and is coupled to a piercing
needle 1108 at its distal end. The piercing needle 1108 may extend
substantially along the longitudinal axis of the syringe 1106. In a
packaged pre-administration state, the piercing needle 1108 may be
covered by a piercing needle cover 1105, which may be removed by a
patient before administration so that the piercing needle 1108 is
uncovered in an administration state. The piercing needle cover
1105 may maintain sterility of the piercing needle and a fluid
conduit formed by and coupled to the piercing needle 1108. In an
exemplary embodiment, removal of the adhesive layer 1104 may also
remove the piercing needle cover 1105.
[0280] An administration interface button 1110 is provided in the
vicinity of the piercing needle 1108. The administration interface
button 1110 holds an administration interface 1112 configured to
administer a therapeutic agent on, in or through the skin to any
desired depth. The administration interface 1112 may be configured
at substantially 90 degrees relative to the piercing needle 1108,
and may include a transfer mechanism that provides a fluid conduit
between the piercing needle 1108 and the administration interface
1112. In an exemplary embodiment, the administration interface 1112
may include a single injection needle (shown as a continuous line
in FIG. 11B). In another exemplary embodiment, the administration
interface 1112 may include two or more injection needles (the
additional needles shown as dashed lines in FIG. 11B). In other
exemplary embodiments, the administration interface 1112 may
include a needle-free pad and/or needle-free patch for performing a
topical administration of a therapeutic agent.
[0281] In a packaged pre-administration state, the administration
interface 1112 may be covered by an administration interface cover
1113, which may be removed by a patient before administration of
the therapeutic agent. In an administration state, the
administration interface 1112 may be uncovered. In an exemplary
embodiment, removal of the adhesive layer 1104 may also remove the
administration interface cover 1113.
[0282] The administration interface button 1110 also includes a
septum 1111 that prevents the piercing needle 1108 from
establishing fluid communication with the fluid conduit in the
administration interface button 1110. A cover 1115 may be provided
to cover the septum 1111 in a pre-administration state, which may
be removed by a patient before administration. In an exemplary
embodiment, the septum cover 1115 and the piercing needle cover
1105 may be coupled so that removal of one also removes the
other.
[0283] In an exemplary embodiment, in a pre and post-administration
state, the piercing needle cover 1105 may cover the piercing needle
1108 and the administration interface button 1110 may be in a
vertically raised position as displaced by the piercing needle
cover 1105 such that the administration interface 1112 is retracted
within the housing 1102. In this state, the septum 1111 of the
administration interface button 1110 may be disposed vertically
above the piercing needle 1108. In addition, the syringe 1106 may
be in a retracted position along the longitudinal axis of the
assembly 1106 spaced from the septum 1111 of the administration
interface button 1110.
[0284] When the piercing needle cover 1105 is removed from the
piercing needle 1108, the administration interface button 1110 is
lowered to a vertically lowered position such that the
administration interface 1112 protrudes outside the housing 1102 at
the administration site. In an exemplary embodiment, the
administration interface button 1110 may be automatically lowered
by the removal of the piercing needle cover 1105. In another
exemplary embodiment, the administration interface button 1110 may
be lowered by the patient pushing downward on the administration
interface button 1110.
[0285] In an exemplary embodiment, the lowering of the
administration interface button 1110 aligns the piercing needle
1108 with the septum 1111 of the administration interface button
1110. The lowering of the administration interface button 1110 also
triggers a syringe actuator that advances the syringe 1106 along
its longitudinal axis toward the septum 1111 of the administration
interface button 1110. This causes the piercing needle 1108 to
pierce the septum 1111 and establish fluid communication with the
administration interface 1112.
[0286] FIGS. 12A and 12B illustrate an exemplary wearable automatic
injection device. FIG. 12A illustrates a side view of the device.
FIG. 12B illustrates a perspective view showing the components of
the device. The automatic injection device 1200 includes a housing
1202 holding a syringe 1204 in a stationary or moveable manner
relative to the housing 1202. An administration interface button
1206 is provided in the housing 1202 in the vicinity of the syringe
1204 and holds an administration interface (not pictured). The
housing 1202 includes an adhesive layer 1208 for attachment at or
near an administration site.
[0287] Other components in the device 1200 similar to the
components in the device 1200 are described with reference to FIGS.
11A and 11B.
[0288] FIGS. 13A-13C illustrate an exemplary wearable automatic
injection device. FIG. 13A illustrates a perspective view of the
device. FIG. 13B illustrates a top view of the device. FIG. 13C
illustrates a side view of the transfer mechanism of the device.
The automatic injection device 1300 includes a housing 1302 having
an adhesive layer 1303 for attachment at or near an administration
site. The housing 1302 holds a cartridge 1304 in a stationary or
moveable manner relative to the housing 1302. The cartridge 1304 is
configured to hold a dose of a therapeutic agent.
[0289] An administration interface button 1306 is provided in the
housing 1302 in the vicinity of the cartridge 1304. The
administration interface button 1306 may hold or be coupled to one
or more administration interfaces 1308 that are configured to
administer a therapeutic agent on, in or through the skin to any
desired depth. The administration interface 1308 may extend
substantially at 90 degrees relative to the longitudinal axis of
the cartridge 1304, and a piercing needle 1310 may extend
substantially parallel to the longitudinal axis of the cartridge
1304. In an exemplary embodiment, the administration interface 1308
may include a single injection needle (shown as a continuous line
in FIG. 13C). In another exemplary embodiment, the administration
interface 1308 may include two or more injection needles (the
additional needles shown as dashed lines in FIG. 13C). In other
exemplary embodiments, the administration interface 1308 may
include a needle-free pad and/or needle-free patch for performing a
topical administration of a therapeutic agent. The administration
interface button 1306 may form or include a transfer mechanism that
establishes fluid communication between the cartridge 1304 to the
administration interface 1308 through the piercing needle 1310.
[0290] The administration interface button 1306 may include a
housing engagement portion 1312 that engages with a housing portion
1314 of the housing 1302 when the administration interface button
1306 is pressed down during administration in an administration
state. In an exemplary embodiment illustrated in FIG. 13C, the
engagement between the housing engagement portion 1312 and the
housing portion 1314 causes the housing portion 1314 to move
parallel to the longitudinal axis of the cartridge 1304 toward the
distal end of the cartridge 1304, thus allowing the piercing needle
1310 to establish fluid communication with the barrel portion of
the cartridge 1304. In another exemplary embodiment, the engagement
between the housing engagement portion 1312 and the housing portion
1314 causes the cartridge 1304 to move parallel to the longitudinal
axis of the cartridge 1304 toward the piercing needle 1310, thus
allowing the piercing needle 1310 to establish fluid communication
with the barrel portion of the cartridge 2004. In another exemplary
embodiment, the engagement between the housing engagement portion
1312 and the housing portion 1314 causes the cartridge 1304 and the
administration interface button 1306 to move toward each other,
thus allowing the piercing needle 1310 to establish fluid
communication with the barrel portion of the cartridge 2004.
[0291] Other components in the device 1300 similar to the
components in the device 1100 are described with reference to FIGS.
11A and 11B.
[0292] FIGS. 14A-14C illustrate an exemplary wearable automatic
injection device including an exemplary cartridge assembly. FIG.
14A illustrates a perspective view of the device. FIG. 14B
illustrates a sectional side view of the cartridge assembly taken
along a longitudinal axis. FIG. 14C illustrates a transparent top
view of the device. The automatic injection device 1400 includes a
housing 1402 having an adhesive layer 1403 for attachment at or
near an administration site. The housing 1402 holds a cartridge
1404 in a stationary or moveable manner relative to the housing
1402. The cartridge 1404 is configured to hold a dose of a
therapeutic agent. A proximal end of the cartridge 1404 includes a
bung 1406 and a distal end of the cartridge 1404 includes a septum
1408 that cooperatively seal the dose within the cartridge
1404.
[0293] An administration interface button 1410 is provided in the
housing 1402 in the vicinity of the cartridge 1404. The
administration interface button 1410 holds an administration
interface at a distal end that extends substantially at 90 degrees
relative to the longitudinal axis of the cartridge 1404. The
administration interface button 1410 is coupled to a transfer
mechanism 1411 that holds a piercing needle 1412 in the vicinity of
the cartridge 1404. The piercing needle 1412 extends substantially
parallel to the longitudinal axis of the cartridge 1404. The
transfer mechanism 1411 includes a fluid conduit to establish fluid
communication between the cartridge 1404 and the administration
interface through the piercing needle 1412. In a pre-administration
state, the piercing needle 1412 may extend partly into a distal end
of the cartridge 1404 but may be spaced from the septum 1408. In an
administration state, the bung 1406 may be moved within the
cartridge 1404 such that the fluid pressure in the cartridge 1404
moves the septum 1408 forward toward the piercing needle 1412. This
causes the piercing needle 1412 to pierce the septum 1408 and
establishes fluid communication between the cartridge 1404 and the
administration interface through the piercing needle 1412.
[0294] Other components in the device 1400 similar to the
components in the device 1100 are described with reference to FIGS.
11A and 11B.
III. Exemplary Administration Systems
[0295] Exemplary embodiments provide different exemplary
administration systems and assemblies for administering a dose of a
therapeutic agent to a patient. In some exemplary embodiments, an
administration interface - coupled to a barrel portion of an
exemplary automatic injection device containing the dose - may be
inserted into or applied to the patient's body to administer the
dose to the patient. In other exemplary embodiments, a piercing
needle may be coupled to a barrel portion containing the dose to
conduct the dose out of the barrel portion, and an administration
interface coupled to the piercing needle may be inserted into or
applied to the patient's body to administer the dose to the
patient.
[0296] In some exemplary embodiments, as illustrated in FIGS. 15
and 16, a syringe may include a barrel portion and an
administration interface coupled to a distal end of the barrel
portion. The administration interface may interface with the
patient's body, e.g., by insertion into or application to the
patient, to administer a therapeutic agent contained in the barrel
portion of the syringe. The administration interface may be aligned
at any suitable angle relative to the longitudinal axis of the
barrel portion ranging from about 0 degrees to about 180 degrees,
but is not limited to this exemplary range.
[0297] FIG. 15 illustrates an exemplary syringe 1500 suitable for
use in an exemplary automatic injection device. The syringe 1500
includes a barrel portion 1502 configured to hold a dose of a
therapeutic agent and extending between a proximal end and a distal
end along a longitudinal axis L. A distal end of the barrel portion
1502 is coupled to one or more administration interfaces 1504 that
extend along the longitudinal axis L. In an exemplary embodiment,
the administration interface 1504 may include a single injection
needle (shown as a continuous line in FIG. 15). In another
exemplary embodiment, the administration interface 1504 may include
two or more injection needles (the additional needles shown as
dashed lines in FIG. 15). In other exemplary embodiments, the
administration interface 1504 may include a needle-free pad and/or
a needle-free patch for performing a topical administration of a
therapeutic agent.
[0298] FIG. 16 illustrates an exemplary syringe 1600 suitable for
use in an exemplary automatic injection device. The syringe 1600
includes a barrel portion 1602 configured to hold a dose of a
therapeutic agent and extending between a proximal end and a distal
end along a longitudinal axis L. A distal end of the barrel portion
1602 may include an elbow portion 1604 that extends substantially
at 90 degrees from the longitudinal axis L. A distal end of the
elbow portion 1604 is coupled to an administration interface 1606
that extends substantially at 90 degrees from the longitudinal axis
L. The administration interface 1606 may be configured to
administer a therapeutic agent on, in or through the skin to any
desired depth. One of ordinary skill in the art will recognize that
exemplary automatic injection devices may include administration
interfaces that extend along the longitudinal axis L of the syringe
or that extend at any suitable angle relative to the longitudinal
axis L of the syringe. Exemplary angles may include, but are not
limited to, about 70 degrees to about 110 degrees. In an exemplary
embodiment, the administration interface 1606 may include a single
injection needle (shown as a continuous line in FIG. 16). In
another exemplary embodiment, the administration interface 1606 may
include two or more injection needles (the additional needles shown
as dashed lines in FIG. 16). In other exemplary embodiments, the
administration interface 1606 may include a needle-free pad and/or
a needle-free patch for performing a topical administration of a
therapeutic agent.
[0299] In some exemplary embodiments, as illustrated in FIGS. 17
and 18, a syringe may include a barrel portion and an
administration interface coupled to a distal end of the barrel
portion. The administration interface may interface with the
patient's body, e.g., by insertion into or application to the
patient's body, to administer a therapeutic agent contained in the
barrel portion of the syringe. The administration interface may be
aligned at any suitable angle relative to the longitudinal axis of
the barrel portion ranging from about 0 degrees to about 180
degrees, but is not limited to this exemplary range.
[0300] In some exemplary embodiments, as illustrated in FIGS. 17
and 18, a syringe may include a barrel portion and an
administration interface coupled directly or indirectly to a distal
end of the barrel portion. The piercing needle may convey a
therapeutic agent contained in the barrel portion of the syringe to
the administration interface, and the administration interface may
administer the therapeutic agent to a patient. A coupling between
the piercing needle and the administration interface may be
provided by one or more intermediate components. An exemplary
coupling component may include, for example, an adapter, provided
between the distal end of the barrel portion and the administration
interface.
[0301] FIG. 17 illustrates an exemplary syringe 1700 suitable for
use in an exemplary automatic injection device. The syringe 1700
includes a barrel portion 1702 configured to extend from a proximal
end to a distal end along a longitudinal axis L and configured to
hold a dose of a therapeutic agent. A distal end of the barrel
portion 1702 is coupled to a piercing needle 1704. The piercing
needle 1704 is, in turn, coupled to one or more administration
interfaces 1706 through an exemplary intermediate adapter 1708. The
administration interface 1706 may be configured to administer a
therapeutic agent on, in or through the skin to any desired depth.
More specifically, a proximal portion of the adapter 1708 is
coupled to the piercing needle 1704 and a distal portion of the
adapter 1708 is coupled to the administration interface 1706. The
adapter 1708 may establish a substantially 90 degree alignment
between the longitudinal axis L of the barrel portion 1702 and the
administration interface 1706. In an exemplary embodiment, the
administration interface 1706 may include a single injection needle
(shown as a continuous line in FIG. 17). In another exemplary
embodiment, the administration interface 1706 may include two or
more injection needles (the additional needles shown as dashed
lines in FIG. 17). In other exemplary embodiments, the
administration interface 1706 may include a needle-free pad and/or
a needle-free patch for performing a topical administration of a
therapeutic agent.
[0302] The exemplary adapter 1708 is a component that includes a
first portion 1710 that extends from the barrel portion 1702
substantially parallel to the longitudinal axis L, and a second
portion 1712 that extends from the first portion 1710 substantially
perpendicular to the longitudinal axis L. More specifically, a
proximal end of the first portion 1710 is coupled to a distal end
of the barrel portion 1702. In an exemplary embodiment, the
proximal end of the first portion 1710 may envelope the distal end
of the barrel portion 1702. A distal end of the first portion 1710
is coupled to a proximal end of the second portion 1712. A distal
end of the second portion 1712 is coupled to a proximal end of the
administration interface 1706. In an exemplary embodiment, the
first portion 1710 and the second portion 1712 of the adapter 1708
may be formed integrally.
[0303] Exemplary adapters may be formed of a rigid material
including, but not limited to, plastic materials, steel, and the
like. Exemplary adapters may alternatively be formed of a flexible
material including, but not limited to, rubber and the like.
[0304] The configuration of the adapter 1708 coupled to the
administration interface 1706 allows the administration interface
1706 to extend at about 90 degrees relative to the longitudinal
axis L of the syringe. This configuration simplifies the
manufacturing of the wearable automatic injection device as it
eliminates the need for a bent administration interface. The
exemplary administration interface 1706 maintains a low profile
against the patient while allowing for proper insertion into or
application to the patient's body. One of ordinary skill in the art
will recognize that exemplary administration interfaces may be bent
from the longitudinal axis of the syringe to any suitable angle not
limited to about 90 degrees, for example, about 70 degrees to about
110 degrees.
[0305] In some exemplary embodiments, one or more fluid conduits
may be disposed between the piercing needle and the administration
interface to allow a flow of the therapeutic agent from the barrel
portion to the administration needle through the piercing needle.
Any suitable fluid conduit or fluid transfer mechanism may be used
to establish the one or more fluid conduits between the piercing
needle and the administration interface. In an exemplary
embodiment, a pierceable septum in its intact state may separate
the piercing needle from fluid communication from the
administration interface. When the piercing needle pierces the
septum during administration in an administration state, fluid
communication may be established between the piercing needle and
the administration interface through the fluid conduit.
[0306] FIG. 18 illustrates a portion of an exemplary automatic
injection device in which a fluid conduit within a transfer
mechanism couples a piercing needle and an administration
interface. The device includes a syringe or cartridge assembly
having a barrel portion 1800 holding a dose of a therapeutic agent.
A distal end of the barrel portion 1800 is coupled to a piercing
needle 1802. A transfer mechanism 1804 is provided in contact with
or in the vicinity of the piercing needle 1802, and also in contact
with or in the vicinity of an administration interface (not
pictured). The transfer mechanism 1804 includes a fluid conduit or
passageway 1806 that establishes fluid communication between the
piercing needle 1802 and the administration interface. In another
exemplary embodiment, the piercing needle and the administration
interface may be coupled directly without an intervening transfer
mechanism.
[0307] In an exemplary embodiment, the transfer mechanism 1804
includes a pierceable septum 1808 that separates the piercing
needle 1802 from the fluid conduit 1806 in the transfer mechanism
1804 before administration in a pre-administration state. In an
exemplary embodiment, during administration in an administration
state, the syringe or cartridge may be moved toward the transfer
mechanism 1804 so that the piercing needle 1802 pierces the septum
1808 to create a fluid communication path among the barrel portion
1800, the fluid conduit 1806 of the transfer mechanism 1804, and
the administration interface. The therapeutic agent may thereby
flow out of the barrel portion 1800 through the piercing needle
1802 into the fluid conduit 1806. The therapeutic agent may then be
transmitted through the fluid conduit 1806 into the administration
interface for administration of the therapeutic agent to a
patient.
[0308] FIG. 19 illustrates an exemplary transfer mechanism 1900 for
providing a fluid conduit 1902 between a piercing needle (not
pictured) and an administration interface (not pictured). The fluid
conduit 1902 may include a centrally extending channel 1904 through
which the therapeutic agent flows from the piercing needle to the
administration interface, and raised wall portions 1906 extending
along the edges of the channel 1904 in order to constrain the fluid
to the channel 1904. The fluid conduit 1902 may take any suitable
form and dimension. In the illustrative embodiment, the fluid
conduit 1902 has a first substantially straight portion 1908
aligned at about 90 degrees from a second substantially straight
portion 1910.
[0309] The fluid conduit 1902 may include a fluid inlet 1912 for
entry of the therapeutic agent from the piercing needle, and a
fluid outlet 1914 for exit of the therapeutic agent into the
administration interface. The fluid inlet 1912 may be coupled
directly or indirectly to the distal end of a piercing needle. In
an exemplary embodiment, a pierceable septum (not pictured) may be
provided at the fluid inlet 1912 to prevent fluid flow from the
piercing needle when the septum is intact, and to allow fluid flow
from the piercing needle when the septum is pierced by the piercing
needle. The fluid outlet 1914 may be coupled directly or indirectly
to the proximal end of the administration interface in order to
establish a fluid flow path between the fluid conduit 1902 and the
administration interface.
[0310] Alternatively, 1912 may be used as the fluid outlet and 1914
may be used as the fluid inlet. In this exemplary embodiment, the
fluid inlet 1914 may be coupled directly or indirectly to a
piercing needle, and the fluid outlet 1912 may be coupled directly
or indirectly to an administration interface.
[0311] The transfer mechanism 1900 may be formed of two housing
portions 1916 and 1918 stacked together. In an exemplary
embodiment, the fluid conduit 1902 may be formed on the surface of
portion 1916, and portion 1918 may be stacked over the fluid
conduit 1902 so as to seal the edges of the fluid conduit 1902 in
order to prevent fluid leakage from the fluid conduit. Compression
between the two housing portions 1916 and 1918 may be provided by
one or more mechanical interlocking mechanism, for example, one or
more fasteners, snaps, chemical bonding, ultrasonic welding, and
others.
[0312] The fluid conduit 1902 may be formed on the surface of the
housing portion 1916 using any suitable technology. In an exemplary
embodiment, the raised wall portions 1906 of the fluid conduit 1902
may be formed of a low durometer material molded as a gasket to
seal the flow path of the therapeutic agent. In another exemplary
embodiment, laser welding may be used to trace a path around the
perimeter of the channel 1904 in order to simultaneously create a
seal around the channel 1904 and bond the two housing portions 1916
and 1918 together.
[0313] In another exemplary embodiment, the piercing needle and the
administration interface may be coupled directly without an
intervening transfer mechanism.
[0314] FIG. 20 illustrates an exemplary transfer mechanism 2000 for
providing a fluid conduit 2002 between a syringe with a piercing
needle 2004 coupled to a barrel portion 2006 and an administration
interface (not pictured). The transfer mechanism 2000 may include a
first portion 2008 having a septum 2010 provided in the vicinity of
the piercing needle 2004.
[0315] The first portion 2008 of the transfer mechanism 2000 may
include an internal hollow space for accommodating the therapeutic
agent and an inlet port 2012 coupled to one end of a hollow tube
2014. Another end of the hollow tube 2014 is coupled directly or
indirectly (for example, through a second portion similar to first
portion 2008) to the administration interface. The hollow tube 2014
provides a fluid path from the piercing needle 2004 to the
administration interface. The hollow tube 2014 may take any
suitable form, alignment and dimension. In the illustrative
embodiment, the hollow tube 2014 extends substantially at right
angles to the longitudinal axis of the barrel portion 2006.
[0316] In an exemplary embodiment, the transfer mechanism 2000 may
be moveable upward and/or downward along the vertical axis. In this
embodiment, before administration in a pre-administration state
(for example, when the piercing needle is covered by a needle
cover), the transfer mechanism 2000 may be in a vertically raised
position above the piercing needle 2004 such that the piercing
needle 2004 is not aligned with the septum 2010 in the transfer
mechanism 2000, thereby preventing fluid communication between the
piercing needle 2004 and the transfer mechanism 2000. At the
beginning of administration (for example, upon removal of the
syringe cover from the piercing needle 2004), the transfer
mechanism 2000 may be automatically lowered to a vertically lowered
position such that the piercing needle 2004 becomes aligned with
the septum 2010 in the transfer mechanism 2000, thus allowing the
piercing needle 2004 to pierce the septum 2010. Exemplary
embodiments may provide any suitable actuation mechanism for
lowering the transfer mechanism 2000 from the vertically raised
position to the vertically lowered position at the beginning of
administration.
[0317] In an exemplary embodiment, the piercing needle 2004 may be
initially coupled to or provided immediately adjacent to the first
portion 2008. In another embodiment, the syringe may be in a
retraction position within the wearable automatic injection device
and the piercing needle 2004 may be initially separated from the
first portion 2008 of the transfer mechanism 2000. In this
embodiment, before administration in a pre-administration state,
the piercing needle 2004 may be separated from the septum 2010 in
the first portion 2008 and may not be in fluid communication with
the transfer mechanism 2000. At the beginning of administration,
the syringe may be moved forwardly by a cartridge or syringe
actuator to an extended position within the device, and the
piercing needle 2004 may pierce the septum 2010, allowing the
therapeutic agent to flow from the barrel portion 2006 to the
transfer mechanism 2000. Exemplary embodiments may provide any
suitable syringe or cartridge actuation mechanism for advancing the
barrel portion and/or the cartridge assembly within the housing
between the retracted position and the extended position in order
to pierce the septum and convey the therapeutic agent to the
patient's body through the administration interface.
[0318] An advantage of the exemplary transfer mechanism 2000 is
that the motions of the piercing needle 2004 and the administration
interface are decoupled and independent from each other. For
example, the mechanism coupling the piercing needle 2004 to the
inlet port 2012 need not take into consideration how this coupling
would affect the outlet of the transfer mechanism 2000 coupled to
the administration interface.
[0319] FIG. 21 illustrates an exemplary transfer mechanism 2100 for
providing a fluid conduit between a syringe having a piercing
needle 2104 coupled to a barrel portion 2106 and an administration
interface (not pictured). The transfer mechanism 2100 may include
an inlet portion (not pictured) couplable to the piercing needle
2104 and an outlet portion (not pictured) couplable to the
administration interface. A hollow tube 2108, for example, a jumper
tube, may be used to couple the inlet portion of the transfer
mechanism to the outlet portion of the transfer mechanism. The
hollow tube 2108 provides a fluid path from the piercing needle
2104 to the administration interface. The hollow tube 2108 may take
any suitable form, alignment and dimension. In the illustrative
embodiment, the hollow tube 2108 extends substantially at right
angles to the longitudinal axis of the barrel portion 2106.
[0320] In an exemplary embodiment, the inlet portion of the
transfer mechanism 2100 may include a septum (not pictured)
provided in the vicinity of the piercing needle 2104. Piercing of
the septum by the piercing needle 2104 may establish fluid
communication between the barrel portion 2106 and the transfer
mechanism 2100. In an exemplary embodiment, the outlet portion of
the transfer mechanism may include a septum (not pictured) provided
in the vicinity of the administration interface. Piercing of the
septum by the administration interface may establish fluid
communication between the transfer mechanism 2100 and the patient's
body.
[0321] In an exemplary embodiment, the transfer mechanism 2100 may
be moveable upward and/or downward along the vertical axis. In this
embodiment, before administration in a pre-administration state
(for example, when the piercing needle is covered by a needle
cover), the transfer mechanism 2100 may be in a vertically raised
position above the piercing needle 2104 such that the piercing
needle 2104 is not aligned with the septum in the transfer
mechanism 2100, thereby preventing fluid communication between the
piercing needle 2104 and the transfer mechanism 2100. At the
beginning of administration (for example, upon removal of the
syringe cover from the piercing needle 2104), the transfer
mechanism 2100 may be automatically lowered to a vertically lowered
position such that the piercing needle 2104 becomes aligned with
the septum in the transfer mechanism 2100, thus allowing the
piercing needle 2104 to pierce the septum. Exemplary embodiments
may provide any suitable actuation mechanism for lowering the
transfer mechanism 2100 from the vertically raised position to the
vertically lowered position at the beginning of administration.
[0322] In an exemplary embodiment, the piercing needle 2104 may be
initially coupled to or provided immediately adjacent to the first
portion 2108. In another embodiment, the syringe may be in a
retraction position within the wearable automatic injection device
and the piercing needle 2104 may be initially separated from the
transfer mechanism 2100. In this embodiment, before administration
in a pre-administration state, the piercing needle 2104 may be
separated from the septum and may not be in fluid communication
with the transfer mechanism 2100. At the beginning of
administration, the syringe may be moved forwardly by a cartridge
or syringe actuator to an extended position within the device, and
the piercing needle 2104 may pierce the septum, allowing the
therapeutic agent to flow from the barrel portion 2106 to the
transfer mechanism 2100. Exemplary embodiments may provide any
suitable syringe or cartridge actuation mechanism for advancing the
barrel portion and/or the cartridge assembly within the housing
between the retracted position and the extended position in order
to pierce the septum and convey the therapeutic agent to the
patient's body through the administration interface.
[0323] In another exemplary embodiment, the piercing needle and the
administration interface may be coupled directly without an
intervening transfer mechanism.
[0324] In the exemplary embodiments illustrated in FIGS. 17-21, a
tight and reliable fluid path conveys the therapeutic agent from
the barrel portion of a syringe or cartridge through a pierced
septum and a tube or channel in a transfer mechanism and eventually
into an administration interface. This configuration allows the
piercing needle assembly and the administration interface assembly
to move independently of each other, which facilitates retraction
of the administration interface into the housing in a
post-administration state after administration has been performed,
while leaving the piercing needle in a position in which it pierces
the septum.
[0325] FIG. 22 illustrates an exemplary syringe or cartridge
actuator 2200 that may be used to advance a syringe 2202 or a
cartridge assembly from a retraction position to an extended
position toward an administration interface within the housing of a
wearable automatic injection device. A proximal end of the syringe
or cartridge assembly may be coupled to a biasing member 2204, for
example, a drive spring, that applies a force on the syringe or
cartridge assembly to move the syringe or cartridge assembly toward
a septum in a transfer mechanism (not pictured). The syringe or
cartridge actuator 2200 may counter the biasing force of the
biasing member, and may hold and lock the barrel portion and/or the
cartridge assembly in a retracted position in a stable and reliable
manner. In an exemplary embodiment in which a syringe is provided,
the syringe may be coupled to a piercing needle that pierces the
septum. In another exemplary embodiment in which a cartridge is
provided, the transfer mechanism may be provided with a piercing
needle that pierces the septum.
[0326] When triggered by a suitable trigger mechanism in an
administration state, the syringe or cartridge actuator 2200 may
allow the syringe or cartridge assembly to move forward toward the
septum under the force of the biasing member. In an exemplary
embodiment, the syringe or cartridge actuator 2200 may be
configured and/or set to a certain distance to control the level of
triggering force required to advance the syringe or cartridge
assembly from the retracted position to the extended position.
[0327] Any suitable trigger mechanism may be used to trigger the
syringe or cartridge actuation systems. In an exemplary embodiment,
the trigger mechanism may automatically trigger the syringe or
cartridge actuation system when the wearable automatic injection
device moves from a pre-administration state to an administration
state. In an exemplary embodiment, the downward vertical movement
of an administration interface button within the housing to provide
a fluid path between the syringe or cartridge assembly and the
administration interface may provide a trigger force to trigger the
plunger actuation system. In another exemplary embodiment, the
forward movement of the syringe or cartridge assembly within the
housing to establish a fluid path between the syringe or cartridge
assembly and the administration interface may provide a trigger
force to trigger the syringe or cartridge system. In another
exemplary embodiment, the syringe or cartridge system may be
manually triggered by a patient.
[0328] Before administration in a pre-administration state, a
piercing needle cover, for example, a rigid needle cover (not
pictured), provided at the distal end of the syringe 2202 may
protectively cover the piercing needle. The piercing needle cover
may maintain sterility of the piercing needle and a fluid conduit
formed by and coupled to the piercing needle. At this stage, since
the piercing needle is covered with the needle cover, the distal
end of the syringe 2202 has a first greater diameter. As such, the
administration interface button including the septum is maintained
in a vertically raised position above the piercing needle cover,
and the septum is not aligned with the piercing needle. When the
piercing needle cover is removed from the syringe in preparation
for administration (for example, manually by a patient or by an
automatic mechanism), the administration interface button is
allowed to lower to a vertically lowered position since it is not
longer kept displaced by the rigid piercing needle cover, and the
septum in the administration interface button is aligned with the
piercing needle. The removal of the piercing needle cover thus
lowers the administration interface button from its vertically
raised position to its vertically lowered position. The lowering of
the administration interface button, in turn, applies a trigger
force to the syringe or cartridge actuator 2200 and operates as the
trigger mechanism for the syringe or cartridge actuator 2200.
[0329] FIG. 23 illustrates an exemplary syringe or cartridge
actuator 2300 including a first portion 2302, a second portion 2304
and a hinge portion 2306 provided between the first and second
portions. The hinge portion 2306 allows the first and second
portions to rotate about the hinge relative to each other. In
different rotational configurations, the first and second portions
may have exemplary angles of between about 0 degrees and about 180
degrees between each other. The actuator 2300 may be coupled to the
syringe and/or the administration interface button. When the septum
and/or the administration interface button is in a vertically
raised position, the actuator 2300 may hold the syringe in place in
its retracted position. When the septum and/or the administration
interface button is in a vertically lowered position, the actuator
2300 may release the syringe so that the biasing member may push
the syringe forward to its extended position in order to pierce the
septum.
IV. Exemplary Plunger Actuation Systems and Administration
Interface Retraction Systems
[0330] Exemplary embodiments provide plunger actuation systems for
actuating a bung in a barrel portion of a wearable automatic
injection device so that the bung moves forwardly within the barrel
portion and expels a dose of a therapeutic agent contained in the
barrel portion. Any suitable trigger mechanism may be used to
trigger the plunger actuation systems. In an exemplary embodiment,
the trigger mechanism may automatically trigger the plunger
actuation system when the wearable automatic injection device moves
from a pre-administration state to an administration state. In an
exemplary embodiment, the downward vertical movement of an
administration interface button within the housing to provide a
fluid path between the syringe or cartridge assembly and the
administration interface may provide a trigger force to trigger the
plunger actuation system. In another exemplary embodiment, the
forward movement of the syringe or cartridge assembly within the
housing to establish a fluid path between the syringe or cartridge
assembly and the administration interface may provide a trigger
force to trigger the plunger actuation system. In another exemplary
embodiment, the plunger actuation system may be manually triggered
by a patient.
[0331] Certain exemplary embodiments provide plunger actuation
systems that cause actuation of the syringe plunger at a fast rate
in order to administer the therapeutic agent to a patient at a fast
rate. Exemplary fast embodiments may administer therapeutic agent
volumes of about 0.1 milliliters to about 1 milliliter in about one
second to about thirty seconds, although exemplary administration
rates are not limited to this exemplary range. In certain exemplary
embodiments, therapeutic agent volumes of about 0.1 milliliters to
about 1 milliliter may be administered in a time duration ranging
from about 3 seconds to about 5 seconds. In certain exemplary
embodiments, therapeutic agent volumes of about 0.1 milliliters to
about 1 milliliter may be administered in a time duration of or
shorter than about 20 seconds. Exemplary embodiments may provide a
linear administration profile for the therapeutic agent so that the
administration rate is substantially constant over time. In some
cases, a linear administration profile may reduce discomfort
experienced by the patient.
[0332] FIG. 24 illustrates an exemplary automatic injection device
2400 that employs a fluid-based plunger actuation mechanism in
which the fluid pressure of a working fluid and/or movement of a
working fluid is used to move a bung within the barrel portion of a
syringe or cartridge. The plunger actuation mechanism includes one
or more fluid circuits to provide a force of the working fluid to a
bung for expressing a dose of a therapeutic agent from a barrel
portion 2404 of a syringe or cartridge. The wearable automatic
injection device 2400 may include a pressure element 2406 that
stores or is coupled to a source of an incompressible working fluid
that provides a fluid pressure. Exemplary working fluids may
include, but are not limited to, water, air, oil, and the like.
Exemplary pressure elements may include, but are not limited to, an
elastic bladder, a master cylinder, a spring-loaded syringe, and
the like.
[0333] The pressure element 2406 may be coupled to a flow
restrictor 2408 via a tubing. The flow restrictor 2408 may restrict
the flow of the working fluid so that the fluid pressure upstream
of the flow restrictor is greater than the fluid pressure
downstream of the flow restrictor. The flow restrictor 2408 may
include an orifice of diameter ranging from about 0.001 inch to
about 0.01 inch, but the diameters of exemplary flow restrictor
orifices are not limited to this exemplary range. The orifice of
the flow restrictor 2408 may have lengths ranging from about 10 mm
to about 50 mm, but the lengths of exemplary flow restrictor
orifices are not limited this exemplary range.
[0334] Exemplary embodiments may configure a number of
characteristics of the administration system to control the total
administration time of the therapeutic agent. Exemplary embodiments
may also configure a number of characteristics of the
administration system based on the viscosity of the working fluid
and/or the therapeutic agent. Exemplary characteristics may
include, but are not limited to, the diameter of the orifice, the
length of the orifice, the viscosity of the working fluid, and the
like. For example, the diameter of the orifice of the flow
restrictor may be decreased to increase the total administration
time.
[0335] The flow restrictor 2408 may be coupled to the bung via a
tubing 2412. When the working fluid is released from the pressure
element 2406 via the flow restrictor 2408, the fluid pressure of
the working fluid drives the bung forwardly within the barrel
portion 2404 in order to expel the dose of the therapeutic agent
from the barrel portion 2404.
[0336] In an exemplary embodiment, before administration in a
pre-administration state, the working fluid may not be released
from the pressure element 2406. In this exemplary embodiment, an
administration trigger (not pictured) may be coupled to the
pressure element 2406 so that, upon activation of the
administration trigger, the working fluid is released from the
pressure element 4106 into the tubings that couple the pressure
element to the bung. The fluid pressure of the working fluid
subsequently advances the bung within the barrel portion 2404, thus
administering the dose to the patient. The fluid circuit
established by the flow of the working fluid and the flow
restrictor thereby provide a regulated force to the bung.
[0337] In an exemplary embodiment, the dose is administered in a
linear administration profile, i.e., at a substantially constant
administration rate. Linearity of the administration profile may be
achieved by the high pressure of the working fluid provided by the
pressure element 2406 upstream of the flow restrictor 2408 and the
damping effect provided by the flow restrictor 2408. The pressure
upstream of the flow restrictor 2408 may be maintained at a high
level relative to projected stick-slip forces such that a highly
damped system is achieved. For the bung to be moved forward within
the barrel portion 2404, the bung would need to pull a vacuum on
the working fluid between the flow restrictor 2408 and the barrel
portion 2404, which is difficult to achieve to an appreciable
extent because the working fluid is essentially incompressible.
[0338] Exemplary damped hydraulic administration circuits allow
movement of the bung via volumetric metering, rather than by a
direct application of force, thereby minimizing stick-slip
phenomena in the administration profile of the therapeutic
agent.
[0339] FIG. 25 illustrates a graph of the cumulative volume of
therapeutic agent (in milliliters) against time (in seconds) as
administered by the exemplary administration system of FIG. 24
including a first exemplary flow restrictor having an exemplary
diameter of about 0.008 inches and an exemplary length of about
34.3 mm The total administration time for administering about 1
milliliter of a therapeutic agent was about 20 seconds. In the
illustrative graph, the administration profile is substantially
linear, i.e., substantially constant over time, and does not
display an initial bolus or abrupt changes or inflections
representative of inconsistent administration rates.
[0340] FIG. 26 is a schematic drawing of an exemplary automatic
injection device 2600 that employs one or more fluid circuits to
provide a force for expressing a therapeutic agent from a cartridge
assembly. FIG. 27 is a top view of the exemplary device 2600. The
exemplary automatic injection device 2600 includes a barrel portion
2602 containing a dose of a therapeutic agent. A distal end of the
barrel portion 2602 is provided in the vicinity of or coupled to a
piercing needle (hidden by a piercing needle cover 2604) that is
protectively covered by a piercing needle cover 2604. The piercing
needle cover 2604 may maintain sterility of the piercing needle and
a fluid conduit formed by and coupled to the piercing needle. The
device 2600 includes an administration interface button that
includes a septum and bears an administration interface (not
pictured). In an exemplary embodiment, the device 2600 may include
an administration interface carrier 2606 for holding the
administration interface. In another exemplary embodiment, the
piercing needle may be coupled directly to the administration
interface without an intermediate carrier component for the
administration interface. In an exemplary embodiment, the
administration interface may be extend substantially orthogonally
to the plane of the device as illustrated, and may be held in place
by the administration interface carrier 2606. An administration
interface lock 2608 may be provided for preventing the
administration interface in a retracted position from protruding
outside the housing once engaged and may be located in the housing
near the administration interface.
[0341] In an exemplary embodiment, a syringe or cartridge actuator
2610 may be provided for advancing the barrel portion 2602 within
the housing toward the septum. A trigger may be provided for
triggering the syringe or cartridge actuator 2610, for example,
when the administration interface button is pressed down or when
the piercing needle cover 2604 is removed.
[0342] In this exemplary embodiment, a master cylinder 2612
containing a working fluid is provided for providing a fluid
pressure to actuate a bung 2614 within the barrel portion 2602. The
master cylinder 2612 may be coupled to an administration trigger
2616 that, when activated, releases the working fluid into fluid
communication with the bung 2614 and allows the fluid pressure to
advance the bung 2614 within the barrel portion 2602.
[0343] Exemplary embodiments also provide administration interface
retraction systems for retracting an administration interface from
a vertically lowered position (or an extended or deployed position)
outside the housing of the device at the patient contact region to
a vertically raised position (or a retracted position) within the
housing of the device. The wearable automatic injection device 2600
includes a retraction mechanism that automatically raises the
administration interface button from an extended or deployed
position within the housing during administration in an
administration state to a retracted position within the housing in
a post-administration state after administration. In an exemplary
embodiment, the retraction mechanism may be a telescoping element.
The master cylinder 2612 may be coupled to a retraction trigger
that, when activated, releases the working fluid into fluid
communication with the retraction mechanism and allows the fluid
pressure to activate the retraction mechanism.
[0344] FIG. 28 illustrates a top view of the device 2600 which
shows a conduit 2802 coupling the master cylinder 2612 to a flow
restrictor 2804, a conduit 2806 coupling the flow restrictor 2804
to the bung in the barrel portion 2602 of the device, and a conduit
2808 coupling the master cylinder 2612 to a retraction mechanism
2810 via a valve 2812, for example, a check valve. FIG. 28
illustrates a schematic diagram of the device 2600.
[0345] The check valve 2812 may have a suitable cracking pressure
at or above which the check valve 2812 allows fluid into the
conduit 2808 coupled to the retraction mechanism 2810. In an
exemplary embodiment, the cracking pressure is higher than the
maximum fluid pressure in the conduit 2806 required to drive the
bung during administration in an administration state. Otherwise,
undesirably, the administration interface retraction process may
begin during or even before administration. In an exemplary
embodiment, the pressure in the conduit 2806 at the end of the
movement of the bung during administration in an administration
state is higher than the cracking pressure. Otherwise, at the end
of the movement of the bung, the pressure in the conduit 2808 may
be insufficient to activate the retraction mechanism 2810. The
volume of the working fluid in the master cylinder 2612 is
sufficient to administer the entire dose of the therapeutic agent
and to activate the retraction mechanism 2810.
[0346] In an exemplary embodiment, the retraction mechanism 2810
and the check valve 2812 may be provided separately. In another
exemplary embodiment, the retraction mechanism 2810 and the check
valve 2812 may be provided as a single element, for example, as an
inverting diaphragm.
[0347] FIG. 30 illustrates a graph of the pressure after the check
valve and behind the bung (in psi) versus time (in seconds) in an
exemplary embodiment. In an exemplary embodiment, the cracking
pressure of the check valve may be about 7.5 psi and the diameter
of the flow restrictor orifice may be about 0.008 inches.
[0348] During administration in an administration state, the flow
restrictor 2804 may cause the pressure in the conduit 2802 to be
about 10 to about 15 psi, while the pressure in the conduit 2806
may be about 5 to about 6 psi. The check valve 2812 thus prevents
any flow of the working fluid from entering the conduit 2808 while
the bung is moving during administration. Once the bung stops
moving at the end of administration, i.e., when the dose has been
expelled from the barrel portion 2602, the pressure in the conduit
2806 increases beyond 7.5 psi. This causes the check valve 2812 to
open, allowing the working fluid to flow into the conduit 2808
which activates the retraction mechanism 2810. The retraction
mechanism 2810 in turn unlocks the administration interface lock
and retracts the administration interface button/carrier 2606
bearing the administration interface. Because it is based on
pressure equalization in the hydraulic circuit, the administration
interface retraction process ensures that the entire dose is
administered before the administration interface is retracted,
maximizes utilization of the therapeutic agent, and minimizes the
overfill required in the barrel portion 2602.
[0349] Any suitable trigger mechanism may be used to trigger the
administration interface retraction systems. In an exemplary
embodiment, the trigger mechanism may automatically trigger the
administration interface retraction system when the wearable
automatic injection device moves from an administration state to a
post-administration state. In an exemplary embodiment, completion
of the administration of a therapeutically effective dose of the
therapeutic agent may trigger the administration interface
retraction system. In another exemplary embodiment, the removal of
the device from the patient before completion of the administration
of a therapeutically effective dose of the therapeutic agent may
trigger the administration interface retraction system. In another
exemplary embodiment, the administration interface retraction
system may be manually triggered by a patient.
[0350] FIG. 31 illustrates a side view of an exemplary automatic
injection device 3100 in which the housing 3102 of the wearable
automatic injection device 3100 includes a skin sensor foot 3104,
which is a structure in an exemplary embodiment housed under or in
the portion of the housing 3102 proximal to the administration
site. In an exemplary embodiment, prior to administration of the
therapeutic agent and during administration, the skin sensor foot
3104 is retained within or forms a portion of the underside of the
housing 3102. When the wearable automatic injection device 3100 is
attached to the administration site and activated, the skin sensor
foot 3104 may be free to move but may be constrained by the
administration site. In an exemplary embodiment, when the wearable
automatic injection device 3100 is removed from the administration
site, regardless of whether administration of the therapeutic agent
was completed, the skin sensor foot 3104 is no longer constrained,
and extends and projects outside the periphery of the housing 3102.
This, in turn, activates a retraction trigger. When the retraction
trigger is activated, a retraction mechanism retracts the
administration interface which may also raise the administration
interface button from the vertically lowered position to the
vertically raised position, so that the administration interface
button protrudes from the top of the housing 3102 and the
administration interface is retracted within the housing 3102.
V. Exemplary Administration Interface Protection Systems
[0351] Exemplary embodiments provide different exemplary
administration interface protection systems for maintaining an
administration interface in a retracted position within the
wearable automatic injection device in a pre-administration state
before administration of a therapeutic agent and in a
post-administration state after administration. Retraction and
protection of the administration interface within the housing of
the device prevents accidental needle sticks from injuring the
patient or any other humans in the vicinity of the wearable
automatic injection device.
[0352] FIGS. 32A and 32B illustrate an exemplary administration
interface protection system 3200 that maintains an administration
interface 3202 in a retracted position within a housing 3204 of an
automatic injection device. Exemplary administration interfaces may
include a single injection needle, a plurality of injection
needles, a needle-free pad, a needle-free patch, and the like.
[0353] In an exemplary embodiment, the administration interface
3202 is movable relative to the housing 3204 away from or toward
the patient's body. When the administration interface 3202 is in a
position within the housing 3204 farther from the patient's body,
the administration interface 3202 is in a retracted position and
does not protrude outside the housing 3204. The administration
interface 3202 is in a retracted position when the device is in a
pre or post-administration state. When the administration interface
3202 is in a position within the housing 3204 closer to the
patient's body, the administration interface 3202 is in an extended
or deployed position and protrudes fully or partly from the housing
3204. The housing 3204 may be provided with an aperture 3206
through which the administration interface 3202 may protrude
outside the housing 3204. The administration interface 3202 is in
an extended or deployed position when the device is in an
administration state.
[0354] The administration interface protection system 3200 employs
a barrier mechanism 3208 which prevents the administration
interface 3202 from protruding from the housing 3204 in a
pre-administration state before administration and in a
post-administration state after administration when the
administration interface 3202 is in the retracted position. FIG.
32A illustrates the system 3200 in which the administration
interface 3202 is in an extended or deployed position and protrudes
fully or partly through the aperture 3206 outside the housing 3204,
for example, during administration in an administration state. In
this case, the barrier mechanism 3208 is displaced away from the
aperture 3206 so that the aperture 3206 is open to the outside of
the housing 3204 and the administration interface 3202 is free to
protrude through the aperture 3206 to the outside of the housing
3204. FIG. 32B illustrates the system 3200 in which the
administration interface 3202 is in a retracted position and does
not protrude from the housing 3204, for example, in a
pre-administration state and a post-administration state.
[0355] In this case, the barrier mechanism 3208 is aligned with and
covers the aperture 3206 so that the aperture 3206 is no longer
open to the outside of the housing 3204 and the administration
interface 3202 is not free to protrude through the aperture 3206 to
the outside of the housing 3204. In an exemplary embodiment, the
barrier mechanism 3208 may be moved rotatably above a point of
rotation between a first position in which it exposes the aperture
3206 (in FIG. 32A) to a second position in which it covers the
aperture 3206 (in FIG. 32B).
[0356] FIGS. 33A and 33B illustrate another exemplary
administration interface protection system 3300 provided in the
housing 3302 of an automatic injection device. The housing 3302 may
be provided with an aperture through which an administration
interface may protrude outside the housing 3302. An exemplary
administration interface may include, but is not limited to, an
injection needle, multiple injection needles, a needle-free patch
or pump, and the like. In an exemplary embodiment, the automatic
injection device includes an administration interface that is
movable relative to the housing 3302 away from or toward the
patient's body along vertical axis V. Exemplary administration
interfaces may include a single injection needle, a plurality of
injection needles, a needle-free pad, a needle-free patch, and the
like. When the device is in a pre- or post-administration state,
the administration interface is in a retracted position farther
from the patient's body and does not protrude outside the housing
3302. When the device is in an administration state, the
administration interface is in an extended or deployed position
closer to the patient's body and protrudes fully or partly outside
the housing 3302. In an exemplary embodiment, the administration
interface may be directly or indirectly coupled to a tab or pin
3308. The tab 3308 is a mechanical member coupled to the
administration interface to enable the administration interface to
be extended when the device is in an administration position, and
that locks the administration interface in a retracted position
when the device is in a pre- or post-administration state.
[0357] The administration interface protection system 3300 includes
a lockout sleeve 3306 provided in the vicinity of the
administration interface for locking the administration interface
in the retracted position in a pre-administration state and a
post-administration state. An exemplary lockout sleeve 3306 is a
substantially tubular or cylindrical member that is capable of
rotating about a central axis of rotation extending through the
member. The lockout sleeve 3006 may include a L-shaped slot or
groove including a first portion 3304 extending along the vertical
axis V and a second portion 3310 extending perpendicular to the
vertical axis V. The tab 3308 is provided to be accommodated within
and to extend through the slot to the outside of the lockout sleeve
3306.
[0358] The administration interface protection system 3300 also
includes a skin sensor foot 3312 that interfaces with the lockout
sleeve 3306 at a wedged interface 3314. The skin sensor foot 3312
may be activated when the wearable automatic injection device 3300
is removed from the administration site. When activated, the skin
sensor foot 3312 may move relative to the interface 3314 to
protrude outside the housing 3302. The movement of the skin sensor
foot 3312 relative to the interface 3314 causes the lockout sleeve
3306 to rotate about its central axis of rotation. Before the skin
sensor foot 3312 is activated, the tab 3308 may be positioned at
the connection between the first and second portions of the slot
(illustrated in FIG. 33A). In this position, the tab 3308 is able
to slide downward along the first portion 3304 of the slot
extending along the vertical axis V. This, in turn, enables the
administration interface to be moved along with the tab 3308 from
the retracted position to the extended position in which the
administration interface may be used to administer a therapeutic
agent to a patient. When the activation of the skin sensor foot
3312 causes rotation of the lockout sleeve 3306, the second portion
3310 of the slot is moved horizontally so that the tab 3308 is
positioned at the terminal end of the second portion 3310 of the
slot (illustrated in FIG. 33B). In this position, the tab 3308 is
no longer free to slide downward along the vertical axis V. This,
in turn, prevents the administration interface to be moved along
with the tab 3308 from the retracted position to the extended
position, and effectively locks the administration interface to the
retracted position within the housing 3302.
[0359] FIG. 34 illustrates an exemplary administration interface
protection system 3400 that maintains an administration interface
held by an administration interface carrier 3402 in a retracted
position within a housing 3404 of an automatic injection device. In
an exemplary embodiment, the administration interface is movable
relative to the housing 3404 away from or toward the patient's body
along the vertical axis V. When the administration interface is in
a position within the housing 3404 farther from the patient's body,
the administration interface may be in a retracted position and may
not protrude outside the housing 3404. In an exemplary embodiment,
the administration interface is in a retracted position when the
device is in a pre or post-administration state. When the
administration interface is in a position within the housing 3404
closer to the patient's body, the administration interface may be
in an extended or deployed position and may protrude fully or
partly from the housing 3404. The housing 3404 may be provided with
an aperture through which the administration interface may protrude
outside the housing 3404. In an exemplary embodiment, the
administration interface is in an extended or deployed position
when the device is in an administration state.
[0360] The administration interface protection system 3400 may
include an administration interface lock 3408 coupled to the
administration interface carrier 3402. In an exemplary embodiment,
the administration interface lock 3408 may be a pivoting or
rotating member that may pivot or rotate about a pivoting point or
interface. An administration interface lock release mechanism 3410
may be provided in the vicinity of or in contact with the
administration interface lock 3408. The administration interface
protection system 3400 may also include a biasing mechanism 3412
that is biased against a skin sensor foot (not illustrated).
[0361] When the device is placed on an administration site, the
skin sensor foot is not activated and the administration interface
lock release mechanism 3410 is in a released position. This
prevents a locking interaction between the administration interface
lock release mechanism 3410 and the administration interface lock
3408, which allows the administration interface carrier 3402 to
move downward along the vertical axis V from the retracted position
to the extended position to protrude outside the housing 3404. When
the skin sensor foot is activated by removal of the device from the
administration site, the biasing mechanism 3412 triggers the
administration interface lock release mechanism 3410 to move
linearly or in a rotary manner so that it interacts with the
administration interface lock 3408 and locks the administration
interface lock 3408. In this position of the administration
interface lock 3408, the administration interface carrier 3402 is
locked in a raised position in which the administration interface
is retracted within the housing 3404.
[0362] In an exemplary embodiment, the piercing needle may be
coupled directly to the administration interface without an
intermediate carrier component for the administration interface. In
another exemplary embodiment, the piercing needle may be coupled to
the administration interface through an intermediate carrier
component for the administration interface.
[0363] FIGS. 35A-35E illustrates another exemplary administration
interface protection system 3500 that maintains an administration
interface held by an administration interface carrier 3502 in a
retracted position within a housing 3504 of an automatic injection
device. FIG. 35A illustrates a perspective view of the system 3500;
FIG. 35B illustrates a top view of the system 3500; FIG. 35C
illustrates a first side view of the system 3500; FIG. 35D
illustrates a second side view of the system 3500 in which the
device is in an administration state; and FIG. 35E illustrates a
second side view of the system 3500 in which the device is in a
pre- or post-administration state.
[0364] The device may include a housing 3504 and an administration
interface carrier 3502 provided in the housing 3504 for holding an
administration interface aligned along the vertical axis V. The
housing 3504 may include an aperture for allowing the
administration interface to protrude outside the housing 3504 and
to administer a therapeutic agent to a patient. Vertical movement
of the administration interface carrier 3502 enables vertical
movement of the administration interface between a retracted
position in which the administration interface does not protrude
outside the housing 3504 (in a pre- or post-administration state of
the device) and an extended position in which the administration
interface protrudes fully or partially outside the housing 3504 at
the administration site on the patient's body (in an administration
state of the device).
[0365] The administration interface carrier 3502 includes a tab or
pin 3516 that extends radially outwardly from the carrier 3502. The
tab 3516 is configured to interact with an administration interface
lock mechanism 3508 when the device is in a pre- or
post-administration state in order to lock the administration
interface carrier 3502 in a vertically raised retracted position.
The administration interface protection system 3500 may include an
administration interface lock mechanism 3508 provided in the
vicinity of or in contact with the administration interface carrier
3502. In an exemplary embodiment, the administration interface lock
3508 may be a pivoting or rotating member that may pivot or rotate
about a pivoting point or interface 3520.
[0366] The administration interface protection system 3500 may
include a biasing mechanism 3506 provided around a biasing
mechanism carrier 3512 that is an elongated mechanical member,
e.g., a metallic bar or rod. The biasing mechanism carrier 3512 may
be coupled to a skin sensor foot 3518. The biasing mechanism
carrier 3512 may also be coupled to a pivot point 3514 of an
administration interface release mechanism 3510 so that rotation of
the biasing mechanism carrier 3512 under the bias of the biasing
mechanism 3506 causes rotation of the administration interface
release mechanism 3510 about the pivot point 3514. In an exemplary
embodiment, the administration interface release mechanism 3510 may
be a separate component from the skin sensor foot 3518. In another
exemplary embodiment, the administration interface release
mechanism 3510 may be a component of the skin sensor foot 3518.
[0367] Placement of the device against an administration site may
cause the skin sensor foot 3518 to be raised toward the housing
3504, thereby causing the biasing mechanism 3506 (and the biasing
mechanism carrier 3512) to rotate in a first direction so that the
administration interface release mechanism 3510 is pivoted into a
position in which the mechanism 3510 does not interact with the
administration interface lock mechanism 3508 in a locking manner.
This results in the administration interface lock mechanism 3508
being maintained in a "down" position so that the administration
interface carrier 3502 is free to move downward to extend the
administration interface outside the housing 3502 to administer a
therapeutic agent.
[0368] Removal of the device from the administration site causes
the skin sensor foot 3518 to extend or protrude outside the housing
3504, thereby causing the biasing mechanism 3506 (and the biasing
mechanism carrier 3512) to rotate in a second direction so that the
administration interface release mechanism 3510 also rotates to a
position in which it interacts with the administration interface
lock mechanism 3508 in a locking manner This results in the
administration interface lock mechanism 3508 being rotated to and
maintained in an "up" position so that the administration interface
carrier 3502 is moved away from the administration site and locked
in place in a vertically raised position so that the administration
interface is in the retracted position and cannot be used to
administer a therapeutic agent.
VI. Exemplary Components and Methods for Maintaining Sterility in
Automatic Injection Devices
[0369] Exemplary embodiments provide exemplary components for use
in automatic injection devices for maintaining sterility of the
therapeutic agent and the therapeutic agent administration pathway
in the devices to avoid the need for aseptic assembly. Exemplary
embodiments also provide automatic injection devices that use the
exemplary components to maintain sterility, and methods for using
automatic injection devices including such components in a manner
that maintains sterility of the devices.
[0370] A sterility barrier is maintained around the therapeutic
agent contained in exemplary automatic injection device and the
administration pathway taken by the therapeutic agent before and
during administration to a patient. In exemplary embodiments, the
barrel portion of a syringe or cartridge for holding the
therapeutic agent may be sterilized prior to filling with the
therapeutic agent. A sterile bung may be placed in the barrel
portion of the syringe or cartridge assembly to seal the
therapeutic agent inside the barrel portion. The containment of the
therapeutic agent inside the wearable automatic injection device by
the sterile barrel portion and the sterile bung maintains sterility
of the therapeutic agent after assembly of the device.
[0371] An administration interface button may be provided between
the barrel portion and an administration interface for
administering the therapeutic agent to the patient. The
administration interface button may include a sterile fluid path
and a sterile pierceable septum provided in the vicinity of an
piercing needle. The sterilized piercing needle (e.g., a single
needle, multiple needles, a needle-free pad, a needle-free patch,
and the like) may be provided in the vicinity of the sterile septum
in the administration interface button for piercing the septum and
establishing fluid communication with the barrel portion. One or
more sterile covers may enclose the septum in the administration
interface button in a sterility barrier. That is, in exemplary
embodiments, the sterile barrel portion, the sterile piercing
needle, the sterile septum and septum cover, the sterile
administration interface, and the administration interface cover
may be cooperatively configured to create a sterility barrier
around the therapeutic agent before and during administration to a
patient. The sterility barrier may eliminate the need for the
patient to swab the septum with alcohol before piercing the septum
during administration of the therapeutic agent, as is
conventionally done.
[0372] Exemplary components for providing a sterility barrier in an
automatic injection device are illustrated in FIGS. 1A, 2A, 6A, and
7A and are described in this section in connection with FIGS. 1A
and 2A. Components of FIGS. 6A and 8A that are similar to the
components of FIGS. 1A and 2A are described in connection with
FIGS. 1A and 2A in this section.
[0373] For example, exemplary devices 100/200 of FIGS. 1A/2A
include a sterile barrel portion 106/206, a sterile piercing needle
120/220, a sterile septum cover 115/215, a sterile administration
interface 118/218 (illustrated as an injection needle), and an
administration interface cover 122/222 (illustrated as a needle
cover). The housing 102/202 of the device 100/200 may include an
adhesive layer 126/226 for attaching the housing 102/202 to the
patient and a protective film 128/228 for protecting the adhesive
layer 126/226. The protective film 128/228 may be sterile in
exemplary embodiments. The removal of the protective film 128/228
exposes the adhesive layer 126/226, allowing the patient to attach
the housing 102/202 to his or her body or an article of clothing by
placing the side with the adhesive layer 126/226 on the body or the
article of clothing.
[0374] Exemplary automatic injection devices may be provided with
components that facilitate in removal of the septum cover and the
administration interface cover before administration. In some
exemplary embodiments, the protective film 128/228 may provide a
mechanism to remove the septum cover and the administration
interface cover in one operation or in one step. The protective
film may include a linking member that is connected to the
administration interface cover 122/222 and the septum cover
115/215. The linking member may include a tether, a tab or other
linkage mechanism.
[0375] When the protective film 128/228 is removed, the linking
member of the protective film 128/228 may remove the administration
interface cover 122/222 and the septum cover 115/215 as well.
[0376] Exemplary devices may provide different mechanisms for
removing the protective film from the housing of the device, and
thereby removing the administration interface cover and the septum
cover at the same time. In exemplary embodiments illustrated in
FIGS. 1A and 2A, a removal mechanism 130/230, e.g., a tab, may be
provided on the protective film 128/228 for removing the protective
film 128/228 from the adhesive layer 126/226. The removal mechanism
130/130 may not be coupled to any portion of the packaging of the
device (e.g., an overwrap, blister pack, bubble wrap, or other
commercial packaging) such that the protective film 128/228 is
still attached to the adhesive layer 126/226 when the device is
removed from the packaging. The removal mechanism 130/230 may be
gripped by the patient and pulled to remove the protective film
128/228 from the adhesive layer 126/226. In exemplary embodiments,
one or more gripping components (e.g., a ring or textured surface)
may be provided at the removal mechanism 130/230 to facilitate
gripping and pulling of the removal mechanism 130/230. In order to
administer the therapeutic agent, the patient may remove the
automatic injection device from its packaging and pull the removal
mechanism 130/230 to remove the protective film 128/228 and expose
the adhesive layer 126/226. When the removal mechanism 130/230 is
pulled to remove the protective film 128/228, the linking member of
the film 128/228 removes the administration interface cover 122/222
and the septum cover 115/215 as well, thus preparing the device for
placement on the patient or his/her clothing for
administration.
[0377] FIG. 36 illustrates another exemplary mechanism for removing
the protective film 128 from the housing 102 of the device 100, and
thereby removing the administration interface cover 122 and the
septum cover 115. FIG. 36 illustrates the exemplary device 100 of
FIG. 1A in a pre-administration state within an outer packaging
3600. The removal mechanism 130 may be provided on the protective
film 128 for removing the protective film 128 from the adhesive
layer 126. The removal mechanism 130 may be attached to an internal
portion 3602 of the outer packaging 3600 of the device (e.g., an
overwrap, blister pack, bubble wrap, or other commercial packaging,
and the like) such that, when the device is removed from the
packaging, the removal mechanism 130 remains attached to portion
3602 and the tugging force on the removal mechanism 130 at portion
3602 removes the protective film 128 from the adhesive layer 126.
That is, when the device is fully outside the packaging, the
protective film 128 has already been removed from the adhesive
layer 126, and the adhesive layer is ready to be applied to the
patient or his/her clothing for administration. In order to
administer the therapeutic agent, the patient may remove the
automatic injection device from its packaging which exposes the
adhesive layer 126 and causes the linking member of the film 128 to
automatically remove the administration interface cover 122, the
piercing needle cover and the septum cover 115, thus preparing the
device for placement on the patient or his/her clothing for
administration. This method of preparing the device for
administering the therapeutic agent may reduce the number of steps
to be performed by the patient and thereby reduce user error.
[0378] FIG. 37 illustrates another exemplary mechanism for removing
the protective film 228 from the housing 202 of the device 200, and
thereby removing the administration interface cover 222 and the
septum cover 215. FIG. 37 illustrates the exemplary device 200 of
FIG. 2A in a pre-administration state within an outer packaging
3700. The removal mechanism 230 may be provided on the protective
film 228 for removing the protective film 228 from the adhesive
layer 226. The removal mechanism 230 may be attached to an internal
portion 3702 of the outer packaging 3700 of the device (e.g., an
overwrap, blister pack, bubble wrap, or other commercial packaging,
and the like) such that, when the device is removed from the
packaging, the removal mechanism 230 remains attached to portion
3702 and the tugging force on the removal mechanism 230 at portion
3702 removes the protective film 228 from the adhesive layer 226.
That is, when the device is fully outside the packaging, the
protective film 228 has already been removed from the adhesive
layer 226, and the adhesive layer is ready to be applied to the
patient or his/her clothing for administration. In order to
administer the therapeutic agent, the patient may remove the
automatic injection device from its packaging which exposes the
adhesive layer 226 and causes the linking member of the film 228 to
automatically remove the administration interface cover 222, the
piercing needle cover and the septum cover 215, thus preparing the
device for placement on the patient or his/her clothing for
administration. This method of preparing the device for
administering the therapeutic agent may reduce the number of steps
to be performed by the patient and thereby reduce user error.
VII. Exemplary Administration Interfaces
[0379] Exemplary embodiments provide exemplary administration
interfaces suitable for use with exemplary automatic injection
devices described above in connection with FIGS. 1-37 for
administering a dose of a therapeutic agent to a patient. Exemplary
embodiments also provide automatic injection devices that use the
exemplary administration interfaces to administer a dose of a
therapeutic agent to a patient. Exemplary administration interfaces
may be provided integrally in an automatic injection device or as a
separate component, e.g., a needle-free patch or an attachment,
couplable to an automatic injection device. Exemplary
administration interfaces may be configured for different types of
administration including, but not limited to, subcutaneous,
intradermal, intramuscular, topical, and the like. The flow rate of
the therapeutic agent achieved by exemplary devices may vary based
on one or more factors including, but not limited to, the type of
application, the therapeutic agent, and the like. For example,
subcutaneous and intramuscular administrations may be conducted at
faster rates than topical, and intradermal administrations. In an
exemplary embodiment, the administration interface may be
configured based on the desired flow rate. For example, the inner
diameter of the administration interface may be increased to
achieve higher flow rates of the therapeutic agent.
[0380] Exemplary administration interfaces may be used to transport
a therapeutic agent into or across biological barriers including,
but not limited to the skin (or parts thereof), the blood-brain
barrier, mucosal tissue (e.g., oral, nasal, vaginal, urethral,
gastrointestinal, respiratory), blood vessels, lymphatic vessels,
cell membranes, and the like. The biological barriers can be in
humans or other types of animals, as well as in plants, insects or
other organisms, including bacteria, yeast, fungi, embryos, and the
like. A target biological barrier may be located within normal,
intact tissue. A target biological barrier may be located within
damaged or diseased tissue, such as a wound or lesion. Exemplary
administration interfaces may be applied to tissue externally or
internally with the aid of a catheter or laparoscope. For certain
applications, such as for administration of a therapeutic agent to
an internal tissue, exemplary administration interfaces may be
surgically implanted. Exemplary embodiments may provide
administration interfaces for administering a therapeutic agent
across biological barriers using microneedle devices.
[0381] Exemplary administration interfaces may include one or more
skin-piercing components configured for administering a therapeutic
agent including, but are not limited to, a single
needle/minineedle/microneedle, multiple
needles/minineedles/microneedles, a needle/minineedle/microneedle
coupled to a tubing, multiple needles/minineedles/microneedles
coupled to a tubing, and the like. The needles, minineedles and/or
microneedles used in exemplary administration interfaces may be
dissolvable in some exemplary embodiments.
[0382] Exemplary administration interfaces may also include one or
more components, e.g., a needle-free pad and/or a needle-free
patch, that may be applied to a patient for performing a topical
administration of a therapeutic agent. An exemplary component for
such applications may include a reservoir in fluid communication
with a barrel portion containing a therapeutic agent, and a
drug-permeable membrane that allows the therapeutic agent from the
reservoir to diffuse through the membrane and onto the skin
surface. Other exemplary components may include flexible or rigid
structures that form a pouch when in contact with the skin, with
the skin forming a surface of the pouch.
[0383] The pouch may fill with the therapeutic agent from the
reservoir, allowing the therapeutic agent to be absorbed by or
diffuse through the skin over extended periods of time. In some
exemplary embodiments, the skin may be pre-treated before an
exemplary administration interface is applied to the skin for a
topical application.
[0384] Exemplary administration interfaces may be formed of any
suitable material including, but not limited to, a polymer material
(e.g., a medical grade polymer), metal, glass, silicone crystals,
and the like. Exemplary administration interfaces may include one
or more injection needles that are hollow and/or that have fluid
channels.
[0385] An exemplary administration interface may have any suitable
dimension, shape and configuration suitable for administering the
dose to the patient by any suitable method including, but not
limited to, intramuscularly, topically, subcutaneously,
intradermally, and the like. Suitable administration interfaces may
have a length configured or selected to provide an administration
depth suitable for the desired therapy. For example, subcutaneous
injections typically penetrate about six to ten millimeters into
the skin. In an exemplary embodiment, the administration interface
may have a length of about twelve mm and may be administered to a
depth of about seven mm into the skin.
[0386] Suitable administration interfaces may have a wall thickness
suitable to provide sufficient mechanism strength, a height, a
diameter suitable to allow a desired flow rate of the therapeutic
agent while minimizing patient sensation, and a tip geometry
suitable for the desired therapy while minimizing patient
sensation. Suitable administration interfaces may be configured as
needed to minimize patient sensation as allowed by therapy. The
length and thickness (gauge) of the injection needle may be
configured based on one or more factors including, but not limited
to, the type of administration (e.g., subcutaneous, intramuscular,
etc.), the age of the patient, the body mass of the patient, the
therapeutic agent, and the like. In some exemplary embodiments,
injection needles for subcutaneous injections may have exemplary
thicknesses of between about 23 gauge and about 25 gauge and
exemplary lengths of between about seven mm and about fifteen mm,
but are not limited to these exemplary ranges. In some exemplary
embodiments, injection needles for intramuscular injections may
have exemplary thicknesses of between about 22 gauge and 25 gauge
and exemplary lengths of between about ten mm and about fifty mm In
some exemplary embodiments, the injection needles may be
micro-needles, i.e., structures having a height above the surface
from which they protrude of about 500 micrometers or less. In some
instances, exemplary micro-needles may have a height of about 250
micrometers or less.
[0387] In some exemplary embodiments, as illustrated in FIGS.
1A-1F, 2A-2F, 6A-6C, 7A-7C, 15-17, 36, and 37 an administration
interface may include a single injection needle. In some other
exemplary embodiments, an administration interface may include a
single injection needle coupled to and in fluid communication with
one or more ducts.
[0388] In exemplary embodiments, the type and dimensions of the
administration interface may be used to configure one or more
aspects of the automatic injection device including, but not
limited to, the housing, the mechanism for applying the device to
the administration site, the internal fluid path and geometry
within the device, and the like.
VIII. Incorporation by Reference
[0389] The entire contents of all references, including patents and
patent applications, cited throughout this application are hereby
incorporated herein by reference in their entirety. The appropriate
components and methods of those references may be selected for the
invention and embodiments thereof. Still further, the components
and methods identified in the Background section are integral to
this disclosure and may be used in conjunction with or substituted
for components and methods described elsewhere in the disclosure
within the scope of the invention.
IX. Equivalents
[0390] In describing exemplary embodiments, specific terminology is
used for the sake of clarity. For purposes of description, each
specific term is intended to at least include all technical and
functional equivalents that operate in a similar manner to
accomplish a similar purpose. Additionally, in some instances where
a particular exemplary embodiment includes a plurality of system
elements or method steps, those elements or steps may be replaced
with a single element or step. Likewise, a single element or step
may be replaced with a plurality of elements or steps that serve
the same purpose.
[0391] Further, where parameters for various properties are
specified herein for exemplary embodiments, those parameters may be
adjusted up or down by 1/20th, 1/10th, 1/5th, 1/3rd, 1/2nd, and the
like, or by rounded-off approximations thereof, unless otherwise
specified. Moreover, while exemplary embodiments have been shown
and described with references to particular embodiments thereof,
those of ordinary skill in the art will understand that various
substitutions and alterations in form and details may be made
therein without departing from the scope of the invention. Further
still, other aspects, functions and advantages are also within the
scope of the invention.
[0392] Exemplary flowcharts are provided herein for illustrative
purposes and are non-limiting examples of methods. One of ordinary
skill in the art will recognize that exemplary methods may include
more or fewer steps than those illustrated in the exemplary
flowcharts, and that the steps in the exemplary flowcharts may be
performed in a different order than shown.
Sequence CWU 1
1
351107PRTArtificialD2E7 light chain variable region 1Asp Ile Gln
Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly1 5 10 15Asp Arg
Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Tyr 20 25 30Leu
Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40
45Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln
Pro65 70 75 80Glu Asp Val Ala Thr Tyr Tyr Cys Gln Arg Tyr Asn Arg
Ala Pro Tyr 85 90 95Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100
1052121PRTArtificialD2E7 heavy chain variable region 2Glu Val Gln
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg1 5 10 15Ser Leu
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr 20 25 30Ala
Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45Ser Ala Ile Thr Trp Asn Ser Gly His Ile Asp Tyr Ala Asp Ser Val
50 55 60Glu Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu
Tyr65 70 75 80Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95Ala Lys Val Ser Tyr Leu Ser Thr Ala Ser Ser Leu
Asp Tyr Trp Gly 100 105 110Gln Gly Thr Leu Val Thr Val Ser Ser 115
12039PRTArtificialD2E7 light chain variable region CDR3 3Gln Arg
Tyr Asn Arg Ala Pro Tyr Xaa1 5412PRTArtificialD2E7 heavy chain
variable region CDR3 4Val Ser Tyr Leu Ser Thr Ala Ser Ser Leu Asp
Xaa1 5 1057PRTArtificialD2E7 light chain variable region CDR2 5Ala
Ala Ser Thr Leu Gln Ser1 5617PRTArtificialD2E7 heavy chain variable
region CDR2 6Ala Ile Thr Trp Asn Ser Gly His Ile Asp Tyr Ala Asp
Ser Val Glu1 5 10 15Gly711PRTArtificialD2E7 light chain variable
region CDR1 7Arg Ala Ser Gln Gly Ile Arg Asn Tyr Leu Ala1 5
1085PRTArtificialD2E7 heavy chain variable region CDR1 8Asp Tyr Ala
Met His1 59107PRTArtificial2SD4 light chain variable region 9Asp
Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Ile Gly1 5 10
15Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Tyr
20 25 30Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
Ile 35 40 45Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe
Ser Gly 50 55 60Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser
Leu Gln Pro65 70 75 80Glu Asp Val Ala Thr Tyr Tyr Cys Gln Lys Tyr
Asn Ser Ala Pro Tyr 85 90 95Ala Phe Gly Gln Gly Thr Lys Val Glu Ile
Lys 100 10510121PRTArtificial2SD4 heavy chain variable region 10Gln
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg1 5 10
15Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr
20 25 30Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Asp Trp
Val 35 40 45Ser Ala Ile Thr Trp Asn Ser Gly His Ile Asp Tyr Ala Asp
Ser Val 50 55 60Glu Gly Arg Phe Ala Val Ser Arg Asp Asn Ala Lys Asn
Ala Leu Tyr65 70 75 80Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr
Ala Val Tyr Tyr Cys 85 90 95Thr Lys Ala Ser Tyr Leu Ser Thr Ser Ser
Ser Leu Asp Asn Trp Gly 100 105 110Gln Gly Thr Leu Val Thr Val Ser
Ser 115 120119PRTArtificial2SD4 light chain variable region CDR3
11Gln Lys Tyr Asn Ser Ala Pro Tyr Ala1 5129PRTArtificialEP B12
light chain variable region CDR3 12Gln Lys Tyr Asn Arg Ala Pro Tyr
Ala1 5139PRTArtificialVL10E4 light chain variable region CDR3 13Gln
Lys Tyr Gln Arg Ala Pro Tyr Thr1 5149PRTArtificialVL100A9 light
chain variable region CDR3 14Gln Lys Tyr Ser Ser Ala Pro Tyr Thr1
5159PRTArtificialVLL100D2 light chain variable region CDR3 15Gln
Lys Tyr Asn Ser Ala Pro Tyr Thr1 5169PRTArtificialVLL0F4 light
chain variable region CDR3 16Gln Lys Tyr Asn Arg Ala Pro Tyr Thr1
5179PRTArtificialLOE5 light chain variable region CDR3 17Gln Lys
Tyr Asn Ser Ala Pro Tyr Tyr1 5189PRTArtificialVLLOG7 light chain
variable region CDR3 18Gln Lys Tyr Asn Ser Ala Pro Tyr Asn1
5199PRTArtificialVLLOG9 light chain variable region CDR3 19Gln Lys
Tyr Thr Ser Ala Pro Tyr Thr1 5209PRTArtificialVLLOH1 light chain
variable region CDR3 20Gln Lys Tyr Asn Arg Ala Pro Tyr Asn1
5219PRTArtificialVLLOH10 light chain variable region CDR3 21Gln Lys
Tyr Asn Ser Ala Ala Tyr Ser1 5229PRTArtificialVL1B7 light chain
variable region CDR3 22Gln Gln Tyr Asn Ser Ala Pro Asp Thr1
5239PRTArtificialVL1C1 light chain variable region CDR3 23Gln Lys
Tyr Asn Ser Asp Pro Tyr Thr1 5249PRTArtificialVL0.1F4 light chain
variable region CDR3 24Gln Lys Tyr Ile Ser Ala Pro Tyr Thr1
5259PRTArtificialVL0.1H8 light chain variable region CDR3 25Gln Lys
Tyr Asn Arg Pro Pro Tyr Thr1 5269PRTArtificialLOE7.A light chain
variable region CDR3 26Gln Arg Tyr Asn Arg Ala Pro Tyr Ala1
52712PRTArtificial2SD4 heavy chain variable region CDR3 27Ala Ser
Tyr Leu Ser Thr Ser Ser Ser Leu Asp Asn1 5
102812PRTArtificialVH1B11 heavy chain variable region CDR3 28Ala
Ser Tyr Leu Ser Thr Ser Ser Ser Leu Asp Lys1 5
102912PRTArtificialVH1D8 heavy chain variable region CDR3 29Ala Ser
Tyr Leu Ser Thr Ser Ser Ser Leu Asp Tyr1 5
103012PRTArtificialVH1A11 heavy chain variable region CDR3 30Ala
Ser Tyr Leu Ser Thr Ser Ser Ser Leu Asp Asp1 5
103112PRTArtificialVH1B12 heavy chain variable region CDR3 31Ala
Ser Tyr Leu Ser Thr Ser Phe Ser Leu Asp Tyr1 5
103212PRTArtificialVH1E4 heavy chain variable region CDR3 32Ala Ser
Tyr Leu Ser Thr Ser Ser Ser Leu His Tyr1 5 103312PRTArtificialVH1F6
heavy chain variable region CDR3 33Ala Ser Phe Leu Ser Thr Ser Ser
Ser Leu Glu Tyr1 5 103412PRTArtificial3C-H2 heavy chain variable
region CDR3 34Ala Ser Tyr Leu Ser Thr Ala Ser Ser Leu Glu Tyr1 5
103512PRTArtificialVH1-D2.N heavy chain variable region CDR3 35Val
Ser Tyr Leu Ser Thr Ala Ser Ser Leu Asp Asn1 5 10
* * * * *