Note: Descriptions are shown in the official language in which they were submitted.
DEVICES, SYSTEMS AND METHODS FOR MEDICAMENT DELIVERY
[1001]
[1002]
Background
[1003] The invention
relates generally to a medical device, and more particularly to a
medicament delivery device for automatically injecting a medicament into a
body of a
patient.
1
Date Recue/Date Received 2021-02-19
[1004] Exposure to certain substances, such as, for example, peanuts,
shellfish, bee
venom, certain drugs, toxins, and the like, can cause allergic reactions in
some individuals.
Such allergic reactions can, at times, lead to anaphylactic shock, which can
cause a sharp
drop in blood pressure, hives, and/or severe airway constriction. Accordingly,
responding
rapidly to mitigate the effects from such exposures can prevent injury and/or
death. For
example, in certain situations, an injection of epinephrine (i.e., adrenaline)
can provide
substantial and/or complete relief from the allergic reaction. In other
situations, for
example, an injection of an antidote to a toxin can greatly reduce and/or
eliminate the
harm potentially caused by the exposure.
[1005] Because emergency medical facilities may not be available when an
individual
is suffering from an allergic reaction, some individuals carry an auto-
injector to rapidly
self-administer a medicament in response to an allergic reaction. Some known
auto-
injectors are cylindrical in shape and include a spring loaded needle to
automatically
penetrate the user's skin and inject the medicament. Such known auto-injectors
can be
bulky and conspicuous, which can make carrying them inconvenient and
undesirable.
Moreover, some known auto-injectors do not have a retractable needle and, as
such, cause
a sharps hazard when injection is complete. Thus, a need exists for an auto-
injector that
can be more conveniently carried by a user and does not present a sharps
hazard upon
completion of the injection.
[1006] Some known auto-injectors include a locking cap at the proximal end
of the
auto-injector to prevent inadvertent actuation and a needle cover at the
distal end of the
auto-injector. Such a configuration can, at times, cause a user to become
confused as to
which end of the auto-injector is the "needle end" (i.e., the distal end) and
which end of
the auto-injector is the "actuation end" (i.e., the proximal end). As such, in
some
situations, a user may mistakenly actuate the known auto-injector away from
the intended
injection site. Such an error can result, for example, in the auto-injector
being actuated
into the user's thumb and/or finger. Furthermore, the locking cap can be
removed prior to
removal of the needle cover, thus allowing the auto-injector to be actuated
before the
needle cover has been removed. A need exists for an auto-injector that can be
actuated
from its distal end. A need also exists for an auto-injector that cannot be
actuated until the
needle cover has been removed.
2
Date Recue/Date Received 2021-02-19
[1007] Some known auto-injectors include a needle cover that collapses or
buckles
when the auto-injector is actuated and the needle breaks through the cover. In
application,
this leaves the needle cover bunched around a portion of the needle, which can
cause the
needle cover to interfere with penetration of the needle into the user. A need
exists for an
auto-injector with a needle cover that will not interfere with consistent
penetration of the
needle.
[1008] Some known auto-injectors use pressurized gas to insert a needle
and/or inject
a medicament into the patient. Such known auto-injectors often do not include
a
mechanism for completely releasing or venting the pressurized gas upon
completion of the
injection event. Thus, a need exists for a gas-powered auto-injector that has
an improved
gas release mechanism.
[1009] Manufacturing techniques of known auto-injectors require much of the
manufacturing process of an auto-injector to occur in a sterile environment.
In particular,
a sterile environment is needed for filling the auto-injector with a
medicament and for
assembly of the auto-injector. Providing and maintaining a sterile environment
during the
entire manufacturing process, however, can be quite expensive. A further need
exists for a
more economical method of manufacturing auto-injectors.
Summary
[1010] Apparatuses and methods for automatic medicament injection are
described
herein. In one embodiment, an apparatus includes a housing, an injection
member at least
partially disposed in the housing, and an actuator configured to be disposed
within the
housing. The actuator is configured to move the injection member between a
first position
and a second position. The actuator includes an energy storage member having a
first
configuration and a second configuration. The energy storage member is
configured to
produce a force when moved from the first configuration to the second
configuration to
move the injection member between its first position and its second position.
Brief Description of the Drawings
[1011] FIG. 1 is a perspective view of a system according to an embodiment
of the
invention.
[1012] FIG. 2 is a front view of a system according to an embodiment of the
invention.
3
Date Recue/Date Received 2021-02-19
[1013] FIG. 3 is a side view of a system according to an embodiment of the
invention.
[1014] FIG. 4 is a cross-sectional view taken along line A-A of FIG. 3 of a
system
according to an embodiment of the invention in a first operative position.
[1015] FIG. 5 is a cross-sectional view taken along line A-A of FIG. 3 of a
system
according to an embodiment of the invention in a second operative position.
[1016] FIG. 6 is a cross-sectional view taken along line A-A of FIG. 3 of a
system
according to an embodiment of the invention in a third operative position.
[1017] FIG. 7 is a cross-sectional view taken along line A-A of FIG. 3 of a
system
according to an embodiment of the invention in a fourth operative position.
[1018] FIG. 8 is a cross-sectional view taken along line A-A of FIG. 3 of a
system
according to an embodiment of the invention in a fifth operative position.
[1019] FIG. 9 is a cross-sectional view taken along line A-A of FIG. 3 of a
system
according to an embodiment of the invention in a sixth operative position.
[1020] FIG. 10 is a flowchart illustrating a method according to an
embodiment of the
invention.
[1021] FIG. 11 is a perspective view of a system according to an embodiment
of the
invention.
[1022] FIG. 12 is a perspective cross-sectional view the system illustrated
in FIG. 11
taken along line B-B of FIG. 11
[1023] FIG. 13 is a perspective view of an apparatus according to an
embodiment of
the invention.
[1024] FIG. 14 is a cross-sectional view of a mechanism according to an
embodiment
of the invention taken along line A-A of FIG. 3.
[1025] FIGS. 15A and 15B are schematic illustrations of an auto-injector
according to
an embodiment of the invention in a first configuration and a second
configuration,
respectively.
4
Date Recue/Date Received 2021-02-19
[1026] FIGS. 16A and 16B are schematic illustrations of an auto-injector
according to
an embodiment of the invention in a first configuration and a second
configuration,
respectively.
[1027] FIG. 17 is a perspective view of an auto-injector according to an
embodiment
of the invention.
[1028] FIG. 18 is a perspective view of the auto-injector illustrated in
FIG. 17 in a first
configuration, with at least a portion of the auto-injector illustrated in
phantom lines for
ease of reference.
[1029] FIG. 19 is a front view of the auto-injector illustrated in FIGS. 17
and 18 in a
first configuration.
[1030] FIG. 20 is a perspective view of the auto-injector illustrated in
FIG. 17 showing
an assembly according to an embodiment of the invention being removed.
[1031] FIG. 21 is a front view of the auto-injector illustrated in FIG. 17
showing a
member according to an embodiment of the invention being removed.
[1032] FIG. 22 is an exploded perspective view of a portion of the auto-
injector
illustrated in FIG. 20.
[1033] FIG. 23 is a cross-sectional view of a component illustrated in FIG.
22.
[1034] FIG. 24 is a perspective view of a component illustrated in FIG. 22.
[1035] FIG. 25 is a perspective view of a member of the auto-injector
illustrated in
FIG. 21.
[1036] FIG. 26 is a perspective view of a portion of the auto-injector
illustrated in
FIGS. 17 and 21.
[1037] FIG. 27 is a perspective view of a portion of the auto-injector
illustrated in
FIGS. 17 and 26.
[1038] FIG. 28 is a partially exploded perspective view of a base of the
auto-injector
illustrated in FIG. 26.
Date Recue/Date Received 2021-02-19
[1039] FIG. 29 is an exploded perspective view of a portion of the auto-
injector shown
in FIG. 19.
[1040] FIG. 30 is a front view of a component of the auto-injector shown in
FIG. 29.
[1041] FIG. 31 is a front view of the auto-injector illustrated in FIG. 19
in a second
configuration.
[1042] FIG. 32 is a perspective view of a portion of the auto-injector
shown in FIG.
31.
[1043] FIGS. 33 and 34 are perspective views of a portion of the auto-
injector shown
in FIG. 32.
[1044] FIG. 35 is a top view of the housing of the auto-injector shown in
FIG. 31.
[1045] FIG. 36 is a cross-sectional view of the housing taken along line 36-
36 in FIG.
35.
[1046] FIG. 37 is front view of the auto-injector illustrated in FIGS. 19
and 31 in a
third configuration.
[1047] FIG. 38 is a front view of the portion of the auto-injector labeled
as 38 in FIG.
37.
[1048] FIG. 39 is a perspective view of a portion of the auto-injector
shown in FIG.
37.
[1049] FIG. 40 is a cross-sectional view of a portion of the auto-injector
as shown in
FIG. 37.
[1050] FIG. 41 is a perspective view of a portion of the auto-injector as
shown in FIG.
37.
[1051] FIG. 42 is an exploded perspective view of a portion the auto-
injector as shown
in FIG. 37.
6
Date Recue/Date Received 2021-02-19
[1052] FIG. 43 is a front view of a portion of the auto-injector
illustrated in FIGS. 19,
31 and 37 in a fourth configuration.
[1053] FIG. 44 is a front view of the auto-injector illustrated in FIGS.
19, 31, 37 and
43 in a fifth configuration.
[1054] FIG. 45 is a front view of the auto-injector illustrated in FIGS.
19, 31, 37, 43
and 44 in a sixth configuration.
[1055] FIG. 46 is a front view of an auto-injector according to an
embodiment of the
invention.
[1056] FIG. 47 is a schematic illustration of an auto-injector according to
an
embodiment of the invention.
[1057] FIG. 48 is a schematic illustration of an auto-injector according to
an
embodiment of the invention.
[1058] FIGS. 49 and 50 are schematic illustrations of an auto-injector
according to an
embodiment of the invention in a first configuration and a second
configuration,
respectively.
[1059] FIGS. 51 and 52 are schematic illustrations of an auto-injector
according to an
embodiment of the invention in a first configuration and a second
configuration,
respectively.
[1060] FIGS. 53-55 are schematic illustrations of an auto-injector
according to an
embodiment of the invention in a first configuration, a second configuration
and a third
configuration, respectively.
[1061] FIGS. 56 and 57 are schematic illustrations of an auto-injector
according to an
embodiment of the invention in a first configuration and a second
configuration,
respectively.
[1062] FIG. 58 is a front view of a portion of an auto-injector according
to an
embodiment of the invention.
7
Date Recue/Date Received 2021-02-19
[1063] FIGS. 59 ¨ 61 are schematic illustrations of an auto-injector
according to an
embodiment of the invention in a first configuration, a second configuration
and a third
configuration, respectively.
[1064] FIGS. 62 and 63 are schematic illustrations of an auto-injector
according to an
embodiment of the invention in a first configuration and a second
configuration,
respectively.
[1065] FIGS. 64 ¨ 66 are schematic illustrations of an auto-injector
according to an
embodiment of the invention in a first configuration, a second configuration
and a third
configuration, respectively.
[1066] FIGS. 67 and 68 are schematic illustrations of a portion of an auto-
injector
according to an embodiment of the invention in a first configuration and a
second
configuration, respectively.
[1067] FIG. 69 is a schematic illustration of an auto-injector according to
an
embodiment of the invention in a first configuration.
[1068] FIGS. 70 ¨ 73 are schematic illustrations of a portion of the auto-
injector in
FIG. 69 in a second configuration, a third configuration, a fourth
configuration and a fifth
configuration, respectively.
[1069] FIG. 74 is a plot showing the pressure within the auto-injector
shown in FIG.
69 as a function of the position of a portion of the auto-injector.
[1070] FIGS. 75 and 76 are perspective views of an auto-injector according
to an
embodiment of the invention in a first configuration and a second
configuration,
respectively.
[1071] FIGS. 77 ¨ 79 are front views of an auto-injector according to an
embodiment
of the invention in a first configuration, a second configuration and third
configuration,
respectively.
[1072] FIG. 80 is a front view of a portion of the auto-injector
illustrated in FIGS. 78
and 79.
8
Date Recue/Date Received 2021-02-19
[1073] FIG. 81 is an exploded perspective view of the portion of the auto-
injector
illustrated in FIG. 80.
[1074] FIGS. 82 and 83 are perspective views of an auto-injector according
to an
embodiment of the invention in a first configuration and a second
configuration
respectively.
[1075] FIG. 84 is a front view of a portion of the auto-injector
illustrated in FIG. 83.
[1076] FIG. 85 is a perspective view of the portion of the auto-injector
illustrated in
FIG. 83.
[1077] FIG. 86 is a flowchart illustrating a method according to an
embodiment of the
invention.
Detailed Description
[1078] Apparatuses and methods for automatic medicament injection and
methods for
manufacturing automatic medicament injectors (also referred to herein as "auto-
injectors")
are described herein.
[1079] In sonic embodiments, an apparatus includes a housing, an injection
member at
least partially disposed in the housing, and an actuator configured to be
disposed within
the housing. The actuator is configured to move the injection member between a
first
position and a second position. The actuator includes an energy storage member
that has a
first configuration and a second configuration. The energy storage member is
configured
to produce a force when moved from the first configuration to the second
configuration to
move the injection member between its first position and its second position.
[1080] In some embodiments, an apparatus includes a movable member
configured to
be disposed within a housing of a medical device and a gas release assembly
coupled to
the movable member. The movable member has a first end portion and a second
end
portion. A portion of the first end portion is configured to define a portion
of a boundary
of a gas chamber. The gas release assembly is configured to selectively allow
fluid
communication between the gas chamber and the area outside the gas chamber.
9
Date Recue/Date Received 2021-02-19
[1081] In some embodiments, an apparatus includes a housing, a needle at
least
partially disposed within the housing, and a guard removably coupled to the
housing. The
guard is configured to cover at least a portion of the needle.
[1082] In some embodiments, an apparatus includes a housing, a medicament
container disposed within the housing and an actuator. The actuator is
configured to be
disposed within the housing and to move the medicament container within the
housing.
The actuator includes a release member and an energy storage member. The
energy
storage member, which can be, for example, a compressed gas container, has a
first
position and a second position. When in the first position, the energy storage
member has
a first potential energy. When in the second position the energy storage
member has a
second potential energy less than the first potential energy. The energy
storage member is
configured to convert a portion of the first potential energy into kinetic
energy when
moved from its first position to its second position to move the medicament
container
within the housing. The energy storage member has a longitudinal axis offset
from a
longitudinal axis of the medicament container. The release member is
configured to
selectively deploy the energy storage member from its first position to its
second position.
[1083] In some embodiments, an apparatus includes a housing, a needle and
an
actuator. The needle has a first end and a second end and defines a
longitudinal axis. The
actuator is configured to be disposed within the housing and to move the
needle between a
first needle position and a second needle position. When in the first needle
position, the
second end of the needle is within the housing. When in the second needle
position, the
second end of the needle is outside the housing. The actuator includes a
release member
and an energy storage member. The energy storage member has a first position
and a
second position. When in the first position, the energy storage member has a
first
potential energy. When in the second position the energy storage member has a
second
potential energy less than the first potential energy. The energy storage
member is
configured to convert a portion of the first potential energy into kinetic
energy when
moved from its first position to its second position to move the needle
between the first
needle position and the second needle position. The energy storage member has
a
longitudinal axis offset from the longitudinal axis of the needle. The release
member is
configured to selectively deploy the energy storage member from its first
position to its
second position.
Date Recue/Date Received 2021-02-19
[1084] In some embodiments, an apparatus includes a housing, a needle, a
medicament container and an actuator. The needle has a first end and a second
end and
defines a longitudinal axis. The actuator is configured to be disposed within
the housing
and to move the needle between a first needle position and a second needle
position.
When in the first needle position, the second end of the needle is within the
housing.
When in the second needle position, the second end of the needle is outside
the housing.
The actuator is further configured to move the medicament container between a
first
medicament container position and a second medicament container position. When
in the
first medicament container position, a lumen defined by the needle is
fluidically isolated
from the medicament container. When in the second medicament container
position, the
first end of the needle is disposed within the medicament container such that
the lumen is
in fluid communication with the medicament container. The actuator includes a
release
member and an energy storage member. The energy storage member has a first
position
and a second position. When in the first position, the energy storage member
has a first
potential energy. When in the second position the energy storage member has a
second
potential energy less than the first potential energy. The energy storage
member is
configured to convert a portion of the first potential energy into kinetic
energy when
moved from its first position to its second position to move the needle
between the first
needle position and the second needle position. The energy storage member has
a
longitudinal axis offset from the longitudinal axis of the needle. The release
member is
configured to selectively deploy the energy storage member from the first
position to the
second position.
[1085] In some embodiments, an apparatus includes an actuator disposable
within a
housing of an auto-injector. The actuator is configured to move a medicament
container
relative to the housing, and includes a gas container, a biasing member and a
puncturcr.
The gas container, which is configured to store a compressed gas, is movable
between a
first position and a second position. The biasing member has a retracted
configuration and
an expanded configuration. The biasing member is configured to engage the gas
container
such that when the biasing member moves from the retracted configuration to
the
expanded configuration the gas container is moved from the first position to
the second
position. The puncturer is configured to penetrate a portion of the gas
container when the
gas container moves to the second position to allow a portion of the
compressed gas to be
11
Date Recue/Date Received 2021-02-19
released from the gas container into a gas chamber defined within the housing
adjacent the
medicament container.
[1086] In some
embodiments, an apparatus includes a housing having a distal end
portion and a proximal end portion, a medicament injector, an energy storage
member and
a retainer. The medicament injector is disposed within the housing and
includes a
medicament container and a needle. The energy storage member, which can be,
for
example, a gas container configured to contain a pressurized gas, is
configured to produce
a force when moved from a first configuration to a second configuration to
move the
medicament injector between a first position and a second position. The
retainer has a
first position and a second position. When the retainer is in its first
position, the retainer is
configured to retain the energy storage member in its first configuration.
When the
retainer is in its second position, the retainer is configured to allow the
energy storage
member to be moved from its first configuration to its second configuration.
The retainer
is configured to be selectively moved from its first position to its second
position by
manipulating an actuator adjacent the distal end portion of the housing.
[1087] In some
embodiments, an apparatus includes a movable member and a valve
coupled to the movable member. The movable member is configured to be disposed
within a housing of a medical device and has a first end portion and second
end portion. A
portion of the first end portion is configured to define a portion of a
boundary of a gas
chamber. The first end
portion defines an opening configured to be in fluid
communication between the gas chamber and an area outside the gas chamber. The
second end portion is configured to be coupled to a needle configured to
deliver a
medicament into a body. The valve is
configured to selectively allow fluid
communication between the gas chamber and the area outside the gas chamber
through the
opening defined by the first end portion of the movable member.
[1088] In some
embodiments, an apparatus includes a movable member, a valve and
an actuator. The valve and the actuator are each coupled to the movable
member. The
movable member is configured to be disposed within a housing of a medical
device and
has a first end portion and second end portion. A portion of the first end
portion is
configured to define a portion of a boundary of a gas chamber. The first end
portion
defines an opening configured to be in fluid communication between the gas
chamber and
12
Date Recue/Date Received 2021-02-19
an area outside the gas chamber. The second end portion is configured to be
coupled to a
needle configured to deliver a medicament into a body. The valve is configured
to
selectively allow fluid communication between the gas chamber and the area
outside the
gas chamber through the opening defined by the first end portion of the
movable member.
The actuator is configured to move the valve between a first position and a
second
position. When the valve is in the first position the gas chamber is
fluidically isolated
from the area outside the gas chamber. When the valve is in the second
position the gas
chamber is in fluid communication with the area outside the gas chamber.
[1089] In some embodiments, an apparatus includes a housing, a medicament
container, a medicament injector, an injection member and a valve. The housing
defines a
gas chamber. The medicament container is configured to be movably disposed
within the
housing and defines a portion of a boundary of the gas chamber. The medicament
injector
includes a seal configured to engage a portion of the housing to fluidically
isolate the gas
chamber from an area outside the gas chamber. A portion of the medicament
injector is
engaged with a medicament container that is movably disposed within the
housing. The
injection member, which can be, for example, a needle, defines a lumen
configured to be
in fluid communication with the medicament container and is configured to
convey a
medicament from the medicament container into a body of a patient. The
medicament
injector has a first position and a second position. When in the first
position, the injection
member is contained within the housing. When in the second position, a portion
of the
injection member extends from the housing. The valve, which can be disposed on
the
medicament injector, has a first configuration and a second configuration.
When the valve
is in the first configuration, the gas chamber is fluidically isolated from
the area outside
the gas chamber. When the valve is in the second configuration, the gas
chamber is in
fluid communication with the area outside the gas chamber.
[1090] In some embodiments, an apparatus includes a housing defining a gas
chamber,
a movable member and a gas release assembly. The movable member has a first
portion
and a second portion. The first portion defines a portion of a boundary of the
gas
chamber. The second portion is configured to be coupled to a needle that can
deliver a
medicament into a body. The movable member is disposable within the housing in
a first
position and a second position. When the movable member is in the first
position, the
needle is disposed within the housing. When the movable member is in the
second
13
Date Recue/Date Received 2021-02-19
position, a portion of the needle extends outside the housing. The gas release
assembly,
which can include, for example, a valve, an actuator and a passageway between
the gas
chamber and an area outside of the gas chamber, has a first configuration and
a second
configuration. When the gas release system is in its first configuration, the
gas chamber is
fluidically isolated from the area outside the gas chamber. When the gas
release system is
in its second configuration, the gas chamber is in fluid communication with
the area
outside the gas chamber. The gas release assembly is configured to be moved
from its
first configuration to its second configuration when the movable member is in
its second
position. The gas release system is further configured to be maintained in its
second
configuration independent of the position of the movable member.
[1091] In some embodiments, an apparatus includes a housing defining a gas
chamber,
a movable member and a valve. The movable member is configured to move
longitudinally within the housing. The movable member has a first portion and
a second
portion. The first portion defines a portion of a boundary of the gas chamber.
The second
portion is configured to move a plunger within a medicament container to expel
a
medicament contained within the medicament container. The valve defines a flow
passageway between the gas chamber and an area outside the gas chamber. The
flow
passageway has a flow area that varies as a function of a longitudinal
position of the
movable member.
[1092] In some embodiments, an apparatus includes a housing, a needle, an
energy
storage member, an actuator, a locking member, and a needle guard. The needle
is
configured to move between a first position and a second position. In its
first position, the
needle is contained within the housing. In its second position, at least a
portion of the
needle extends from the housing. The energy storage member has a first
configuration and
a second configuration and is configured to produce a force when moving
between its first
configuration and its second configuration to move the needle from its first
position to its
second position. The actuator is configured to move the energy storage member
from its
first configuration to its second configuration. The locking member is movably
coupled to
the distal end portion of the housing such that the locking member can be
moved between
a first position and a second position. In its first position, the locking
member is
configured to engage the actuator to prevent the actuator from moving the
energy storage
member to the second configuration. The needle guard is removably coupled to
at least
14
Date Recue/Date Received 2021-02-19
one of the distal end portion of the housing or a base movably coupled to the
distal end
portion of the housing.
[1093] In some embodiments, an apparatus includes a housing and a safety
guard. The
safety guard includes a locking portion and a needle guard portion. The
locking portion is
configured to inhibit actuation of a medicament delivery device. The needle
guard portion
is configured to substantially cover a needle of the medicament delivery
device. The
safety guard has a first position and a second position. In its first
position, the safety guard
is configured to be selectively coupled to at least one of the housing or a
base movably
coupled to the housing. In its second position, the safety guard is removed
from the
housing.
[1094] In some embodiments, an apparatus includes a needle guard configured
to
cover at least a portion of a needle of a medical injector. The needle guard
is configured
to substantially prevent microbes from passing through the needle guard. The
needle
guard is configured to allow a sterilant gas to pass through the needle guard.
[1095] In some embodiments, an apparatus includes a housing, a medicament
injector,
and a porous needle guard. The medicament injector is disposable within the
housing and
includes a needle. The needle has a first position and a second position. In
its first
position, the needle is contained within the housing. In its second position,
at least a
portion of the needle extends from the housing. The porous needle guard is
removably
coupled to the distal end portion of the housing. The porous needle guard is
constructed
from a microbial resistant material.
[1096] A method of manufacturing an automatic medicament injector includes
inserting at least a portion of a needle into a needle hub disposed in a
housing. A needle
cover is installed over at least a portion of the needle to substantially
cover a portion of the
needle extending from the needle hub. The needle is sterilized after the
needle cover is
installed over at least a portion of the needle.
[1097] FIG. 1 is a perspective view, FIG. 2 is a front view, and FIG. 3 is
a side view,
of a system 1000 according to the invention, which can comprise a housing
1100, which,
in some embodiments, can comprise a handheld portion 1800 separated via an
actuation
guard 1200 from an actuation bar 1300. Actuation guard 1200 can prevent
accidental
Date Recue/Date Received 2021-02-19
activation of system 1000. Housing 1100 can be constructed of a durable
material, such as
stainless steel, aluminum, polycarbonate, etc., to protect a compressed gas
container,
medicament, injection apparatus and/or user of system 1000. The injection
apparatus can
be actuated by a fluid pressure, such as pressure provided by the compressed
gas, which
upon completion of actuation can escape housing 1100 via gas escape opening,
such as via
status indicator 1400.
[1098] A status of a system 1000 can be determined via status indicator
1400, which
can provide a view, such as via a UV blocking, photo-sensitive, and/or
translucent
window, into an interior of housing 1100. Viewable through the window can be a
status
of medicament carried by housing 1100, a location of a needle and/or injection
apparatus
for the medicament, and/or an activation status of system 1000. For example,
if the
medicament has aged to the point of discoloration, which aging might or might
not render
the medication useless, harmful, etc., status indicator 1400 can allow that
situation to be
determined. In some embodiments, gas can escape housing 1100 via status
indicator 1400
and/or another opening in housing 1100.
[1099] Some embodiments of system 1000 can provide a compact medicament
delivery mechanism that can efficiently and/or rapidly deliver a prescribed
dose. The
length (L) and width (W) of system 1000 can be similar to that of a credit
card, and the
thickness (T) can be less than one inch. Thus, some embodiments of system 1000
can
provide a conveniently carried, easy-to-use, easy to activate drug delivery
apparatus that
can require little to no training to safely carry, use, and/or dispose of.
[1100] To assist a user in positioning system 1000 in a correct orientation
for
injection, system 1000 and/or housing 1100 can provide various tactile clues.
For
example, a top 1110 of housing 1100 can be rounded, and a bottom 1120 of
actuation bar
1300 of housing 1100 can be flat. Other tactile clues are also possible, such
as bulges,
ribs, grooves, gaps, roughened surfaces, indentations, etc.
[1101] FIG. 4 is a cross-sectional view taken along line A-A of FIG. 3 of
an
embodiment of a system 1000 in a first operative position. FIGS. 5, 6, 7, 8,
and 9 show
system 1000 of FIG. 4 in second, third, fourth, fifth, and sixth operative
positions,
respectively.
16
Date Recue/Date Received 2021-02-19
[1102] System 1000 can comprise a housing 1100, handheld portion 1800,
actuation
guard 1200, and/or actuation bar 1300. System 1000 can comprise system
actuator 2000,
gas reservoirs 3000, medicament actuator 4000, medicament storage assembly
5000,
medicament carrier 9000, needle assembly 6000, use indicator 7000, and/or gas
vent
mechanism 8000, etc.
[1103] Upon removal, release, rotation, and/or relocation of actuation
guard 1200,
system actuator 2000 can be adapted to rapidly discharge an actuating portion
of a
contents of a compress gas container. For example, system actuator 2000 can
comprise a
compressed gas container 2400, which initially can contain a compressed gas
2500, an
actuating portion of which can be released from container 2400 by penetration
of a gas
port 2600 via a point of a puncturer 2700. Upon removal and/or relocation of
actuation
guard 1200, actuation bar 1300 can be moved closer to and/or in contact with
handheld
portion 1800. Upon removal and/or relocation of actuation guard 1200, gas
container
2400 can be brought into contact with puncturer 2700 via extension of a pre-
compressed
spring 2300 and/or movement of an actuation stick 2200. Thus, actuation guard
1200 can
prevent accidental activation of system 1000 and/or unintended discharge of an
actuating
portion of the contents 2500 of gas container 2400.
[1104] Once gas port 2600 has been punctured, an actuating portion of
compressed gas
2500 can escape from container 2400 and flow via gas reservoirs 3000, such as
gas
channel 3100. The flowing gas can meet and/or apply gas pressure to medicament
actuator 4000, which can comprise a pusher 4100, which can travel within a
sleeve 1500
defined by walls 1520. Sleeve 1500 can be constructed of metal, stainless
steel,
aluminum, plastic, polycarbonate, etc. Seals 4200, such as o-rings, can resist
gas leakage,
such as past pusher 4100 and/or out of housing 1100. Thus, pusher 4100 can
function as a
piston traveling within a cylinder, although it is not necessarily required
that the cross-
sectional shape of sleeve 1500 be round.
[1105] Medicament actuator 4000 can interface with medicament storage
assembly
5000. For example, medicament actuator 4000 can comprise a plurality of
plungers 4300,
each of which can be capped with a piston 4400 which can sealingly slide
and/or move
within a corresponding vial 5100 containing a liquid medicament 5200. For
example, in
response to pressure applied by an actuating portion of the contents 2500 of
compressed
17
Date Recue/Date Received 2021-02-19
gas container 2400, pusher 4100 can cause plungers 4300 and/or pistons 4400 to
simultaneously move. The number of corresponding sets of plungers 4300,
pistons 4400,
and/or vials 5100 can be 2, 3, 4, 5, 6, or more. Pistons 4400 can be
constructed of a
resilient, durable, and/or sealing material, such as a rubber. Each plunger
4300 from the
plurality of plungers can define a longitudinal axis, the longitudinal axes
(e.g., axes 4310,
4320, 4330, 4340) of the plurality of plungers can be parallel, non-coaxial,
and/or co-
planar.
[1106] Each vial 5100 from the plurality of vials can be substantially
cylindrical with a
substantially round and/or substantially elliptical cross-sectional shape.
Thus, each vial
5100 can define a longitudinal axis, the longitudinal axes of the plurality of
vials can be
parallel, non-coaxial, and/or co-planar. The longitudinal axis of each vial
can be co-axial
with the longitudinal axis of its corresponding plunger.
[1107] Each vial can be capped at one end with a frangible seal 5300, which
can be
burst when piston 4400 generates sufficient pressure upon medicament 5200,
thereby
allowing at least a portion of medicament 5200 to flow out of vial 5100 and
into
medicament carrier 9000. Thus, the plurality of vials can be fluidly
coupleable to the
actuating portion of the contents 2500 of gas container 2400.
[1108] Medicament carrier 9000 can hold each of vials 5100 and can travel
within
sleeve 1500. Medicament carrier 9000 can comprise a plurality of channels 9200
adapted
to receive medicament 5200 as it exits its respective vial 5100, and direct
medicament
5200 to a common conduit 9300. Medicament carrier 9000 can interface with
needle
assembly 6000 and/or use indicator 7000.
[1109] From common conduit 9300, medicament 5200 can enter needle assembly
6000, such as into a single needle 6100 via which medicament can approach
needle tip
6200. As medicament actuator 4000 and/or medicament carrier 9000 are driven
toward
actuator bar 1300, needle tip 6200 can penetrate an end 6400 of needle sheath
6300 and
exit actuator bar 1300 at needle port 1340.
[1110] Referring to FIG. 5, upon movement of actuation bar 1300 closer to
handheld
portion 1800, sheath seat 1330 can come in contact with sheath tip 6400,
thereby causing
sheath 6300 to buckle and/or crumble. As actuator bar 1300 comes in contact
with
18
Date Recue/Date Received 2021-02-19
handheld portion 1800, bar stop 1320 can approach medicament carrier stop
9400, while
carrier spring 1600 is compressed.
[1111] Referring to FIG. 6, as at least a portion of contents 2500 of gas
container 2400
escapes, it can flow through channel 3100. The gas, which can still be
relatively
pressurized, can begin to accumulate behind pusher 4100 to form an expanding
gas
chamber 3200 and to cause medicament actuator 4000, medicament storage
assembly
5000, and medicament carrier 9000 to slide together within sleeve 1500. As
medicament
actuator 4000, medicament storage assembly 5000, and medicament carrier 9000
slide
closer to actuator bar 1300, spring 1600 becomes increasingly compressed
between bar
stop 1320 and medicament carrier stop 9400. As medicament actuator 4000,
medicament
storage assembly 5000, and medicament carrier 9000 slide closer to actuator
bar 1300,
needle tip 6200 can extend further from actuator bar 1300 and sheath 6300 can
become
further compressed and/or deformed. At its ultimate extension point, needle
tip 6200 can
extend from housing 1100 from approximately 0.25 millimeters to approximately
20
millimeters, including all values and subranges therebetween, such as up to
approximately
2 millimeters, greater than approximately 5 millimeters, from approximately
5.13
millimeters to approximately 9.98 millimeters, etc.
[1112] Referring to FIG. 7, as gas chamber 3200 continues to expand,
medicament
carrier 9000 can be driven until medicament carrier stop 9400 contacts
actuator bar stop
1300 thereby resisting further travel of medicament carrier 9000. At that
point, additional
expansion of gas chamber 3200 can cause medicament actuator 4000, pusher 4100,
plungers 4300, and/or pistons 4400 to initiate travel with respect to
medicament storage
assembly 5000, thereby generating an expulsion pressure in vials 5100, and/or
thereby
rupturing frangible seals 5300 and allowing medicament 5200 to enter
medicament carrier
9000, and begin flowing through medicament channels 9200, medicament conduit
9300,
needle 6100, and/or out needle tip 6200 and into a patient. Alternatively,
frangible seals
5300 can be replaced and/or augmented by a frangible seal located at or near
where
medicament conduit 9300 couples to needle 6100. Frangible seals 5300 can be
constructed of a thin, taught, resilient, durable, and/or sealing material
potentially having a
predetermined yield strength, such as a rubber, such as chromo butyl rubber,
and/or of a
relatively brittle material potentially having a predetermined yield strength,
such as
ceramic, certain plastics, such as polystyrene, etc.
19
Date Recue/Date Received 2021-02-19
[1113] As medicament carrier stop 9400 contacts actuator bar stop 1320,
medicament
carrier hooks 9600 can engage with engagement receivers 7100 in use indicator
7000.
[1114] Referring to FIG. 8, as gas chamber 3200 continues to expand,
medicament
actuator 4000, pusher 4100, plungers 4300, and/or pistons 4400 can continue
moving until
they complete their travel within medicament storage assembly 5000, thereby
expelling a
predetermined dose of medicament 5200 from vials 5100, out of needle assembly
6000,
external to housing 1100, and/or into the patient. As gas chamber 3200 reaches
its
maximum size, medicament actuator 4000, pusher 4100, plungers 4300, and/or
pistons
4400 can continue moving until they complete their travel with respect to
medicament
carrier 9000, thereby causing gas release actuator 9700 to engage with gas
relief valve
8200. Engagement of gas release actuator 9700 with gas relief valve 8200 can
cause gas
within gas chamber 3200 to exit gas chamber 3200, discharge away from pistons
4400,
and/or exhaust from system 1000 and/or housing 1100, such as via status
indicator 1400
and/or a gas escape port located on housing 1100).
[1115] Referring to FIG. 8 and FIG. 9, as sufficient gas is vented from gas
chamber
3200, the pressure applied by the gas in gas chamber 3200 can decrease until
the force
applied by the gas on medicament actuator 4000 is less than the force of
compressed
spring 1600. Thus, spring(s) 1600 can begin to expand, thereby moving
medicament
carrier 9000, vial assembly 5000, and medicament actuator 4000 away from
actuator bar
1300 and helping to exhaust gas from gas chamber 3200. As medicament carrier
9000
moves, use indicator 7000 can travel with it, due to the engaged relationship
of
medicament carrier hooks 9600 and engagement receivers 7100 and/or engagement
catches 7200 in use indicator 7000. As use indicator 7000 moves away from
actuation bar
1300, sheath 6300 can travel with it, thereby creating a gap between sheath
tip 6400 and
needle port 1340, and thereby exposing a previously non-visible colored
portion 1350 of
actuation bar 1300 and/or providing an indication that system 1000 has been
used (and
likely substantially exhausted of its medicament), thereby discouraging any
further
attempts to use system 1000.
[1116] As medicament carrier 9000 moves away from actuator bar 1300, needle
6100
can retract into sheath 6300 which un-buckles and/or un-deforms towards its
original
shape. Eventually, needle 6100 can retract completely within the boundaries of
housing
Date Recue/Date Received 2021-02-19
1100, thereby tending to prevent accidental needle sticks after the initial
injection and/or
potentially reducing and/or eliminating a sharps hazard.
[1117] In some embodiments, system actuator 2000 can comprise a finger
triggered,
twistable, pivotable, and/or lever-operated mechanism. For example, system
actuator
2000 can comprise a twistable handle that can screw into gas port 2600. In
some
embodiments, system actuator 2000 can be a finger trigger located on a side of
the
housing.
[1118] FIG. 10 is a flowchart of an embodiment of a method 10000 for
operating a
medicament delivery apparatus. At activity 10100, an actuation lock for the
apparatus is
released. At activity 10200, an actuating portion of the contents of a
compressed gas
container are released. At activity 10300, via pressure provided by the
released gas, a
needle is extended from the apparatus. At activity 10400, via pressure
provided by the
released gas, a piston applies pressure to a medicament stored in one of a
plurality of vials.
At activity 10500, a frangible seal containing the medicament in the vial is
burst. At
activity 10600, the medicament flows from the vial, through the needle, and
into a patient.
At activity 10700, once a predetermined dose is expelled and/or injected, the
needle is
withdrawn from the patient and/or retracted into the pre-use bounds of the
apparatus. At
activity 10800, the apparatus is rendered unusable for additional injections
and/or
indicated as previously utilized.
[1119] FIG. 11 is a perspective view of an embodiment of system 1000,
showing
actuation guard 1200 removed from housing 1100, so that actuation guard 1200
no longer
separates actuator bar 1300 from handheld portion 1800. Actuation guard 1200
can
comprise a grippable portion 1220 that can be gripped by a user to pull
actuation guard
1200 away from housing 1100, thereby allowing system 1000 to be activated,
such as via
slapping actuator bar 1300 against a thigh of the user. Actuation guard 1200
can comprise
an actuation stick separator portion 1240, that can keep separate actuation
stick prongs
2240 when actuation guard 1200 is installed on housing 1100. Actuation guard
1200 can
comprise a guard portion 1260 that can separate actuator bar 1300 from
handheld portion
1800 when system 1000 is not in use and/or when system 1000 has not been used.
[1120] FIG. 12 is a perspective cross-sectional view taken along line B-B
of FIG. 11,
and FIG. 13 is a perspective view of an embodiment of actuation stick 2200.
Referring to
21
Date Recue/Date Received 2021-02-19
FIGS. 12 and 13, system 1000 can comprise housing 1100, actuation bar 1300,
and system
actuator 2000, which can comprise prong squeezer 1390, actuation stick 2200,
prong
retainer 2100, spring 2300, upper spring retainer 2260, gas container 2400,
gas port 2600,
and/or puncturer 2700. When actuation bar 1300 is pressed firmly against a
user's body,
such as via slapping housing actuation bar against the user's thigh, buttocks,
and/or arm,
prong squeezer 1390 can urge prong tips 2220 of prongs 2240 of actuation stick
2200
toward one another. Note that prong tips 2200 can have a triangular, wedge,
angular,
and/or frusto-conical shape. As prongs tips 2220 slide along the angled V-
groove of prong
squeezer 1390, prong catches 2230 can substantially lose contact with prong
retainer 2100.
This can allow compressed spring 2300 to rapidly urge actuation stick 2200 and
gas
container 2400 toward puncturer 2700, which can penetrate gas port 2600,
thereby
allowing gas to escape from gas container 2400. Although any of many different
types of
gas containers can be utilized, an example of a suitable gas container can be
obtained from
Leland Limited, Inc. of South Plainfield, NJ.
[1121] FIG. 14 is a cross-sectional view of an embodiment of gas venting
mechanism
8000 of system 1000 taken along line A-A of FIG. 3. System 1000 can comprise
handheld
portion 1800, actuator bar 1300, sleeve 1500. As pistons 4440 near the limit
of their
travels, medicament 5200 can be expelled along medicament path 5900, which can
extend
past frangible seal 5300, through medicament channels 9200, medicament conduit
9300,
and needle 6100, and into the body of a user, such as subcutaneously,
intramuscularly,
and/or at a depth of from approximately 0.25 millimeters to approximately 20
millimeters,
including all values and subranges therebetween, such as up to 2 millimeters,
greater than
millimeters, etc
[1122] As pistons 4440 near the limit of their travels, engagement of gas
release
actuator 9700 with gas relief valve 8200 can cause compressed spring 8300 to
move valve
arm such that o-ring 8400 is urged away from its seat 8500. This movement can
reveal a
passage 8600, via which gas can exit gas chamber 3200 along gas exhaust path
8900,
which can extend between sleeve inner walls 1520 and outer walls 9100 of
medicament
carrier 9000. Eventually, gas exhaust path 8900 can extend between handheld
portion
1800 and actuator bar 1300. Likewise, an alternative embodiment of valve 8200,
made of
rubber or any other resilient material, can be placed across seat 8500 to
provide a seal that,
22
Date Recue/Date Received 2021-02-19
once gas release actuator 9700 interacts with valve 8200, allows valve 8200 to
bend or
flap upwards away from seat 8500, causing the gas to escape via passage 8600.
[1123] FIGS. 15A and
15B are schematic illustrations of an auto-injector 2002
according to an embodiment of the invention in a first configuration and a
second
configuration, respectively. The auto-
injector 2002 includes a housing 2110, a
medicament container 2262, a movable member 2312, a gas relief valve 2328 and
a
compressed gas source 2412. The medicament container 2262, which can be, for
example,
a pre-filled cartridge, a vial, an ampule or the like, is fixedly disposed
within the housing
2110 and defines a longitudinal axis Lm. The medicament container 2262
contains a
medicament 2268, such as, for example, epinephrine.
[1124] The movable
member 2312 includes a proximal end portion 2316 and a distal
end portion 2318. The proximal end portion 2316 includes a surface 2322 that,
together
with the housing 2110, defines a gas chamber 2120. Said another way, the
surface 2322
defines a portion of a boundary of the gas chamber 2120. The proximal end
portion 2316
defines an opening 2326 therethrough, which is in fluid communication between
the gas
chamber 2120 and an area outside of the gas chamber 2128. The distal end
portion 2318
is movably disposed within the medicament container 2262 along the
longitudinal axis
Lm, as shown by the arrow A. A needle 2212 is coupled to the distal end 2318
of the
movable member 2312. The needle 2212 defines a lumen (not shown) and a side
opening
2215.
[1125] The gas
relief valve 2328 is coupled to the movable member 2312 such that it
can selectively allow fluid communication between the gas chamber 2120 and the
area
outside of the gas chamber 2128. The gas relief valve 2328 can include, for
example, a
movable membrane, a frangible seal, a spring-loaded gas relief valve body or
the like.
[1126] In use, when
the auto-injector 2002 is actuated, the gas chamber 2120 is placed
in fluid communication with the compressed gas source 2412, thereby allowing a
pressurized gas to flow into the gas chamber 2120. In response to a force
produced by the
pressurized gas on the surface 2322 of the movable member 2312, the movable
member
2312 moves within the housing 2110 and the medicament container 2262, as
indicated by
arrow A. As a result, as shown in FIG. 15B, the needle 2212 is extended
through the
housing 2110. The movement of the movable member 2312 also forces the
medicament
23
Date Recue/Date Received 2021-02-19
2268 through the side opening 2215 and into the lumen (not shown) defined by
the needle
2212. In this manner, the medicament injection occurs while the needle 2212 is
being
extended from the housing 2110 (i.e., while the needle 2212 is being inserted
into the
body).
[1127] In use, the pressure of the pressurized gas within the gas chamber
2120 can be
controlled by the gas relief valve 2328. As shown in FIG. 15B, the gas relief
valve 2328 is
actuated as indicated by the arrow B, thereby allowing pressurized gas to flow
from the
gas chamber 2120 to the area outside of the gas chamber 2128 through the
opening 2326,
as shown by the arrows g. Although the gas relief valve 2328 is shown as being
actuated
after substantially all of the medicament 2268 has been injected, in other
embodiments, the
gas relief valve 2328 can be actuated at any time during the injection event.
For example,
in some embodiments, the gas relief valve 2328 can be actuated as the
injection event is
beginning to control the rate of needle insertion and/or medicament injection.
In other
embodiments, the gas relief valve 2328 can be actuated at the end of the
injection event to
allow the needle 2212 to be retracted to a position within the housing 2110.
In yet other
embodiments, the gas relief valve 2328 can be actuated upon completion of the
injection
event to prevent residual gas from undesirably building up within the gas
chamber 2120.
[1128] FIGS. 16A and 16B are schematic illustrations of an auto-injector
12002
according to an embodiment of the invention in a first configuration and a
second
configuration, respectively. The auto-injector 12002 includes a housing 12110
that
contains a medicament container 12262, an energy storage member 12410, a
release
member 12540 and an injection member 12212. The medicament container 12262,
which
can be, for example, a pre-filled cartridge, a vial, an ampule or the like, is
movably
disposed within the housing 12110. The medicament container 12262 contains a
medicament 12268, such as, for example, epinephrine. As illustrated, the
medicament
container 12262 can be moved, as indicated by arrow B in FIG. 16B, along its
longitudinal
axis Lm between a first position (FIG. 16A) and a second position (FIG. 16B).
When the
medicament container 12262 is in its first (or retracted) position, the
medicament container
12262 is spaced apart from the injection member 12212. When the medicament
container
12262 is in the second (or advanced) position, the medicament container 12262
is placed
in fluid communication with the injection member 12212. In this manner, when
the
medicament container 12262 is in the second (or advanced) position, the
medicament
24
Date Recue/Date Received 2021-02-19
12268 can be conveyed via the injection member 12212 from the medicament
container
12262 into a body of a patient. The injection member 12212 can be, for
example, a
needle, a nozzle or the like.
[1129] The energy storage member 12410, which can be any suitable device
for
storing energy, such as, for example, a spring, a battery, a compressed gas
cylinder or the
like, is also movably disposed within the housing 12110. As shown, the energy
storage
member 12410 defines a longitudinal axis Le that is offset from the
longitudinal axis Lm
of the medicament container 12262. The energy storage member 12410 can be
moved, as
indicated by arrow A in FIG. 16B, within the housing 12110 along its
longitudinal axis Le
between a first position (FIG. 16A) and a second position (FIG. 16B). When the
energy
storage member 12410 is in its first position, the energy storage member 12410
has a first
potential energy. When the energy storage member 12410 is in its second
position, the
energy storage member 12410 has a second potential energy that is less than
the first
potential energy. When the energy storage member 12410 moves from its first
position to
its second position, it converts at least a portion of its first potential
energy into kinetic
energy to move the medicament container 12262 between its first position and
its second
position.
[1130] Said another way, the movement of the energy storage member 12410
from its
first position to its second position results in the production of a force
that acts upon the
medicament container 12262 to move the medicament container 12262 between its
first
position and its second position. The non-coaxial relationship between the
longitudinal
axis Lm of the medicament container 12262 and the longitudinal axis Le of the
energy
storage member 12410 allows the medicament container 12262 and the energy
storage
member 12410 to be arranged within the housing 12110 in any number of
different
configurations. In this manner, the auto-injector 12002 can have any number of
different
sizes and shapes, such as, for example, a substantially rectangular shape.
[1131] The release member 12540 is disposed within the housing 12110 and is
configured to selectively deploy the energy storage member 12410 from its
first position
to its second position. The release member 12540 can be any suitable mechanism
for
moving the energy storage member 12410, such as, for example, a mechanical
linkage, a
Date Recue/Date Received 2021-02-19
spring-loaded rod or the like. In this manner, a user can actuate the auto-
injector by
manipulating a portion of the release member 12540.
[1132] FIG. 17 is a perspective view of an auto-injector 3002 according to
an
embodiment of the invention in a first configuration. The auto-injector 3002
includes a
housing 3110 having a proximal end portion 3112 and a distal end portion 3114.
The
distal end portion 3114 of the housing 3110 includes a protrusion 3142 to help
a user grasp
and retain the housing 3110 when using the auto-injector 3002. Said another
way, the
protrusion 3142 is configured to prevent the auto-injector 3002 from slipping
from the
user's grasp during use. A base 3520 is movably coupled to the distal end
portion 3114 of
the housing 3110. A needle guard assembly 3810 is removably coupled to the
base 3520.
Similarly, a safety lock 3710 is removably coupled to the base 3520. To inject
a
medicament into the body, the distal end portion 3114 of the housing is
oriented towards
the user such that the base 3520 is in contact with the portion of the body
where the
injection is to be made. The base 3520 is then moved towards the proximal end
3112 of
the housing 3110 to actuate the auto-injector 3002. The housing 3110 also
includes a
transparent status window 3118 (see FIG. 36) to allow a user to determine the
status of the
auto-injector 3002 or the medicament contained therein.
[1133] FIG. 18 is a perspective view of the auto-injector 3002 showing the
housing
3110 in phantom lines so that the components contained within the housing 3110
can be
more clearly seen. For clarity, FIG. 18 shows the auto-injector 3002 without
the needle
guard assembly 3810 and the safety lock 3710. Similarly, FIG. 19 is a front
view of the
auto-injector 3002 showing the housing 3110 in phantom lines. The auto-
injector 3002
includes a medicament injector 3210 and a movable member 3312 engaged with the
medicament injector 3210, each of which are disposed within the housing 3110.
The auto-
injector 3002 also includes a system actuator 3510, a compressed gas container
3412 and a
gas release mechanism 3612.
[1134] The medicament injector 3210 includes a carrier 3250 that is movable
within
the housing 3110, a medicament container 3262 and a needle 3212. The
medicament
container 3262 is coupled to the carrier 3250. The needle 3212 is disposed
within a needle
hub portion 3223 (see FIG. 22) of the carrier to allow the needle 3212 to be
placed in fluid
communication with the medicament container 3262 during an injection event.
26
Date Recue/Date Received 2021-02-19
[1135] The movable
member 3312 includes a proximal end portion 3316 and a distal
end portion 3318 The proximal end portion 3316 includes a surface 3322 that,
together
with the housing 3110, defines a gas chamber 3120. Said another way, the
surface 3322
defines a portion of a boundary of the gas chamber 3120. The distal end
portion 3318 is
disposed within the medicament container 3262. In use, the movable member 3312
moves
towards the distal end portion 3114 of the housing 3110, as indicated by arrow
C, in
response to a force produced by a pressurized gas on the surface 3322 of the
movable
member 3312. As a result, the movable member 3312 and the medicament injector
3250
are moved towards the distal end portion 3114 of the housing 3110, thereby
exposing the
needle 3212 from the housing 3110. The movable member 3312 then continues to
move
within the medicament container 3262 to expel a medicament from the medicament
container 3262 through the needle 3212.
[1136] The auto-
injector 3002 is actuated by the system actuator 3510, which is
configured to move the compressed gas container 3412 into contact with the gas
release
mechanism 3612. The gas release mechanism 3612 punctures a portion of the
compressed
gas container 3412 to release the pressurized gas contained therein into the
gas chamber
3120 defined by the housing 3110.
[1137] The system
actuator 3510 includes a rod 3540, a spring 3560 and a spring
retainer 3570. The rod 3540 has a proximal end portion 3542 and a distal end
portion
3544. The proximal end portion 3542 of the rod 3540 is coupled to the
compressed gas
container 3412. The distal end portion 3544 of the rod 3540 is coupled to the
spring
retainer 3570 by two projections 3548, which can be moved inwardly towards
each other
to decouple the rod 3540 from the spring retainer 3570, as discussed below.
[1138] The spring
3560 is disposed about the rod 3540 in a compressed state such that
the spring 3560 is retained by the proximal end portion 3542 of the rod 3540
and the
spring retainer 3570. In this manner, the rod 3540 is spring-loaded such that
when the
distal end portion 3544 of the rod 3540 is decoupled from the spring retainer
3570, the
force of the spring 3560 causes the rod 3540, and therefore the compressed gas
container
3412, to move proximally as indicated by arrow D and into contact with the gas
release
mechanism 3612.
27
Date Recue/Date Received 2021-02-19
[1139] The base 3520 defines an opening 3522 (shown in FIG. 26) configured
to
receive a portion of the projections 3548 when the base is moved towards the
proximal
end 3112 of the housing 3110, as indicated by arrow E. When the projections
3548 are
received within the opening 3522, they are moved together causing the distal
end portion
3544 of the rod 3540 to be released from the spring retainer 3570. In some
embodiments,
the opening 3522 extends though at least a portion of the base 3520. In some
embodiments, the opening 3522 extends completely through the base 3520, for
example,
such that a locking portion of a safety guard (discussed in detail below) can
be inserted
through the opening.
[1140] As shown in FIGS. 18 and 19, the medicament injector 3210 defines a
longitudinal axis Lm that is non-coaxial with the longitudinal axis Le defined
by the
compressed gas container 3412. Accordingly, the medicament injector 3210, the
compressed gas container 3412 and the system actuator 3510 are arranged within
the
housing 3110 such that the housing has a substantially rectangular shape.
Moreover, the
non-coaxial relationship between the medicament injector 3210 and the
compressed gas
container 3412 allows the auto-injector 3002 to be actuated by manipulating
the base
3520, which is located at the distal end portion 3114 of the housing 3110.
[1141] As discussed above, the use and actuation of the auto-injector 3002
includes
several discrete operations. First, the auto-injector 3002 is enabled by
removing the
needle guard 3810 and the safety lock 3710 (see FIGS. 20 and 21). Second, the
auto-
injector 3002 is actuated by moving the base 3520 proximally towards the
housing 3110.
Third, when actuated, the compressed gas container 3412 engages the gas
release
mechanism 3612, which causes the pressurized gas to be released into the gas
chamber
3120 (see FIG. 31). Fourth, the pressurized gas produces a force that causes
the movable
member 3312 and the medicament injector 3210 to move distally within the
housing 3110
(see FIG. 37). The movement of the medicament injector 3210 causes the needle
3212 to
extend from distal end portion 3114 of the housing 3110 and the base 3520.
This
operation can be referred to as the "needle insertion" operation. Fifth, when
the
medicament injector 3210 has completed its movement (i.e., the needle
insertion operation
is complete), the movable member 3312 continues to move the medicament
container
3262 distally within the carrier 3250. The continued movement of the
medicament
container 3262 places the needle 3212 in fluid communication with the
medicament
28
Date Recue/Date Received 2021-02-19
container 3262, thereby allowing the medicament to be injected (see FIG. 43).
Sixth, the
force from the pressurized gas causes the movable member 3312 to move within
the
medicament container 3262, thereby expelling the medicament through the needle
3212
(see FIG. 44). This operation can be referred to as the "injection operation."
Seventh,
upon completion of the injection, the pressurized gas is released from the gas
chamber
3120, thereby allowing the medicament injector 3210 and the movable member
3312 to be
moved proximally within the housing. This operation can be referred to as the
"retraction
operation" (see FIG. 45). A detailed description of the components contained
in the auto-
injector 3002 and how they cooperate to perform each of these operations is
discussed
below.
[1142] Prior to use, the auto-injector 3002 must first be enabled by first
removing the
needle guard 3810 and then removing the safety lock, or locking member, 3710.
As
illustrated by arrow G in FIG. 20, the needle guard 3810 is removed by pulling
it distally.
Similarly, as illustrated by arrow H in FIG. 21, the safety lock 3710 is
removed by pulling
it substantially normal to the longitudinal axis Le of the compressed gas
container 3412.
Said another way, the safety lock 3710 is removed by moving it in a direction
substantially
normal to the direction that the needle guard 3810 moved or to the
longitudinal axis Lm of
the needle (as shown in FIG. 20) is moved. As described in more detail herein,
in some
embodiments, the needle guard 3810 and the safety lock 3710 are cooperatively
arranged
to prevent the safety lock 3710 from being removed before the needle guard
3810 has been
removed. Such an arrangement prevents the auto-injector 3002 from being
actuated while
the needle guard 3810 is in place.
[1143] As illustrated in FIG. 22, the needle guard 3810 includes a sheath
3820 and a
sheath retainer 3840. The sheath 3820 has a proximal end portion 3822 and a
distal end
portion 3824 and defines an opening 3826 configured to receive a portion of
the needle
3212 when the needle guard 3810 is in a first (or installed) position. Said
another way, the
sheath 3820 is an inner member of the needle guard 3810 configured to
substantially cover
at least a portion of the needle 3212 when the needle guard is in a first
position, and the
sheath retainer 3840 is an outer member of the needle guard.
[1144] As illustrated in FIG. 23, the sheath 3820 further defines a
recessed portion
3828 within the opening 3826 that engages a corresponding protrusion 3238
defined by an
29
Date Recue/Date Received 2021-02-19
outer surface 3236 of the needle hub 3223. In this manner, when the needle
guard 3810 is
in its first position, the sheath 3820 is removably coupled to the needle hub
3223. In some
embodiments, the recessed portion 3828 and the protrusion 3238 form a seal
that is
resistant to microbial penetration.
[1145] The sheath 3820 can be constructed from any suitable material. For
example
the sheath can be constructed from polyethylene, including high density
polyethylene,
polypropylene, polytetrafluoroethylene, thermoplastic polyurethane, rubber or
any other
elastomer or polymer. In some embodiments, the sheath 3820 is constructed from
a rigid
material. A rigid needle sheath can reduce the likelihood of needle sticks
during the
manufacturing process and can inhibit crumpling of the sheath around the
needle during
insertion of the needle into bodily tissue. In other embodiments, the sheath
can be
constructed from a flexible material. In some embodiments, the sheath 3820 is
constructed from a material configured to resist or substantially prevent
microbial
penetration therethrough, and thus can maintain sterility of a needle received
therein.
[1146] The sheath 3820 can be configured for use with one or more
sterilization
methods. In other words, the sheath can be configured to allow sterilization
of the needle
when the sheath is disposed over the needle and coupled to the needle hub. In
some
embodiments, the sheath 3820 is configured to allow a sterilant gas or other
sterilizing
agent to pass therethrough. For example, the sheath can include a valve
configured to
allow passage of the sterilant gas. In another example, the sheath is
constructed of a
porous material, such as a porous material configured to allow passage of the
sterilant gas
through the material while preventing microbes from passing therethrough.
[1147] The sheath retainer 3840 has a proximal portion 3842 and a distal
portion 3844.
The proximal portion 3842 of the sheath retainer 3840 includes a protrusion
3856 that
engages a corresponding recess 3526 in the base 3520 (see FIG. 28) to
removably couple
the sheath retainer 3840 to the base 3520. The distal portion 3844 of the
sheath retainer
3840 defines an opening 3846 through which the distal end portion 3824 of the
sheath
3820 is disposed. The distal portion 3844 of the sheath retainer 3840 includes
a series of
retaining tabs 3852 that engage the distal end portion 3824 of the sheath 3820
to couple
the sheath 3820 to the sheath retainer 3840. In this manner, when the sheath
retainer 3840
is moved distally away from the base 3520 into a second (or removed) position,
as shown
Date Recue/Date Received 2021-02-19
in FIG. 20, the sheath 3820 is removed from the needle 3212. Moreover, this
arrangement
allows the sheath 3820 to be disposed about the needle 3212 independently from
when the
sheath retainer 3840 is coupled to the sheath 3820. As such, the two-piece
construction of
the needle guard provides flexibility during manufacturing, for example,
because the
sheath retainer can be installed after the sheath has been disposed about the
needle and the
needle sterilized. The distal portion 3844 of the sheath retainer 3840 also
includes a
protrusion 3848 to aid the user when grasping the needle guard 3810.
[1148] When the needle guard 3810 is in its first (or installed) position,
the sheath
retainer 3840 is disposed within a recess 3720 defined by one of the extended
portions
3716 of the safety lock 3710 (see FIG. 25). This arrangement prevents the
safety lock
3710 from being removed when the needle guard 3810 is in its first position,
which in
turn, prevents the auto-injector 3002 from being actuated when the needle
guard 3810 is in
its first position.
[1149] The outer surface of the needle guard 3810 (or sheath retainer 3840
specifically) includes an indicia 3850 to instruct the user in operating the
auto-injector
3002. As shown in FIG. 24, the indicia 3850 includes a numeral to indicate the
order of
operation and an arrow to indicate the direction in which the needle guard
3810 should be
moved. In some embodiments, the indicia 3850 can include different colors,
detailed
instructions or any other suitable indicia to instruct the user. In other
embodiments, the
indicia 3850 can protrude from the sheath retainer 3840 to aid the user when
grasping the
needle guard 3810.
[1150] After the needle guard 3810 is removed, the user must then remove
the safety
lock 3710, as indicated in FIG. 21. As shown in FIG. 25, the safety lock 3710
is a U-
shaped member having a first end 3712 and a second end 3714. The second end
3714 of
the safety lock 3710 includes two extended portions 3716, each of which
includes an
inwardly facing protrusion 3718. When the safety lock 3710 is in its first (or
locked)
position, the extended portions 3716 extend around a portion of the base 3520
to space the
base 3520 apart from the distal end portion 3114 of the housing 3110. As shown
in FIG.
26, the protrusions 3718 are configured engage a portion of the base 3520 to
removably
couple the safety lock 3710 in its first position.
31
Date Recue/Date Received 2021-02-19
[1151] One of the extended portions 3716 defines a recess 3720 that
receives the
sheath retainer 3840 when the needle guard 3810 is in its first position, as
discussed above.
Although only one extended portion 3716 is shown as including a recess 3720,
in some
embodiments both extended portions 3716 can include a recess 3720 to receive
the sheath
retainer 3840. The safety lock 3710 can be engaged with the needle guard 3810
to prevent
movement of the safety lock 3710 when the needle guard 3810 is in place in any
suitable
manner. For example, in some embodiments, the sheath retainer includes
protrusions that
are received within corresponding openings defined by the safety lock. In some
embodiments, the safety lock includes protrusions that are received within
corresponding
openings defined by the sheath retainer.
[1152] The first end 3712 of the safety lock 3710 includes a locking
protrusion 3722
that extends inwardly. As shown in FIG. 26, when the safety lock 3710 is in
its first
position, the locking protrusion 3722 extends between the projections 3548 of
the rod
3540 and obstructs an opening 3522 of the base 3520. In this manner, when the
safety
lock 3710 is in its first position, the base 3520 cannot be moved proximally
to allow the
projections 3548 to be received within the opening 3522. The arrangement of
the locking
protrusion 3722 also prevents the projections 3548 from being moved inwardly
towards
each other. Accordingly, when the safety lock 3710 is in its first position,
the auto-
injector 3002 cannot be actuated.
[1153] The outer surface 3724 of the first end 3712 of the safety lock 3710
includes a
series of ridges 3726 to allow the user to more easily grip the safety lock
3710. The outer
surface 3724 of the first end 3712 of the safety lock 3710 also includes an
indicia 3728 to
instruct the user in operating the auto-injector 3002. As shown in FIG. 25,
the indicia
3728 includes a numeral to indicate the order of operation and an arrow to
indicate the
direction in which the safety lock 3710 should be moved. In some embodiments,
the
indicia 3728 can include different colors, detailed instructions or any other
suitable indicia
to instruct the user. In other embodiments, the indicia 3728 can protrude from
the safety
lock 3710 to aid the user when grasping the safety lock 3710.
[1154] After being enabled, the auto-injector 3002 can then be actuated by
moving the
base 3520 proximally towards the housing 3110, as indicated by arrow I in FIG.
27. As
shown in FIGS. 28 and 36, the base 3520 defines two openings 3536 that receive
32
Date Recue/Date Received 2021-02-19
corresponding attachment protrusions 3150 disposed on the distal end portion
3114 of the
housing 3110. In this manner, the movement and/or alignment of the base 3520
relative to
the housing 3110 is guided by the attachment protrusions 3150 and the openings
3536 (see
FIG. 36).
[1155] Each attachment protrusion 3150 is secured within its corresponding
opening
3536 by a lock washer 3534. The lock washers 3534 each define an opening 3535
that
receives a portion of the attachment protrusion 3150. The lock washers 3534
are disposed
within slots 3533 defined by the base 3520 so that the openings 3535 are
aligned with the
attachment protrusions 3150. The openings 3535 are configured to allow the
lock washers
3534 to move proximally relative to the attachment protrusions 3150, but to
prevent
movement of the lock washers 3534 distally relative to the attachment
protrusions 3150.
In this manner, when the attachment protrusions 3150 are disposed within the
openings
3535 of the lock washers 3534, the base 3520 becomes fixedly coupled to the
housing
3110. Moreover, after the base 3520 is moved proximally relative to the
housing 3110,
the lock washers 3534 prevent the base 3520 from returning to its initial
position. Said
another way, the arrangement of the lock washers 3534 prevents the base 3520
from being
"kicked back" after the auto-injector 3002 has been actuated.
[1156] The base 3520 also defines a needle opening 3532, a recess 3526 and
two
retraction spring pockets 3531. The needle opening 3532 receives a portion of
the needle
guard 3810 when the needle guard is in its first position. Additionally, when
the auto-
injector is in its third configuration (see FIG. 37), the needle 3212 extends
through the
needle opening 3532. As described above, the recess 3526 receives the
corresponding
protrusion 3856 on the sheath retainer 3840 to removably couple the needle
guard 3810 to
the base 3520. As will be described in more detail herein, the retraction
spring pockets
3531 receive a portion of the retraction springs 3350.
[1157] As shown in FIG. 28, the base 3520 includes two opposing tapered
surfaces
3524 that define an opening 3522 configured to receive a corresponding tapered
surface
3550 of the projections 3548 when the base is moved proximally towards the
housing
3110. The opening 3522 can extend through the base 3520 or through at least a
portion of
the base. When the projections 3548 arc received within the tapered opening
3522, they
are moved together as indicated by arrows J in FIG. 27. The inward movement of
the
33
Date Recue/Date Received 2021-02-19
projections 3548 causes the rod 3540 to become disengaged from the spring
retainer 3570,
thereby allowing the rod 3540 to be moved proximally along its longitudinal
axis as the
spring 3560 expands. A more detailed description of the components included in
the
system actuator 3510 is provided below with reference to FIGS. 29 and 30.
[1158] The system
actuator 3510 includes a rod 3540, a spring 3560 disposed about
the rod 3540 and a spring retainer 3570. As described in more detail herein,
the spring
retainer 3570 retains both the spring 3560 and the rod 3540. The spring
retainer 3570
includes a first surface 3572, a second surface 3574 and a series of outwardly
extending
engagement tabs 3576. The spring retainer 3570 is disposed within the gas
container
opening 3124 defined by the housing 3110 (see FIG. 36) such that the
engagement tabs
3576 engage the interior surface 3123 of the housing 3110 to produce an
interference fit.
In this manner, the spring retainer 3570 is fixedly disposed within the
housing 3110.
[1159] The rod 3540
has a proximal end portion 3542 and a distal end portion 3544.
The distal end portion 3544 of the rod 3540 includes two extensions 3552
disposed apart
from each other to define an opening 3554 therebetween. Each extension 3552
includes a
projection 3548 having a tapered surface 3550 and an engagement surface 3549.
When
the rod 3540 is in its first (or engaged) position, the engagement surfaces
3549 engage the
second surface 3574 of the spring retainer 3570 to prevent the rod 3540 from
moving
proximally along its longitudinal axis. As described above, when the base 3520
is moved
proximally towards the housing 3110, the tapered surfaces 3550 of the
projections 3548
cooperate with the corresponding tapered surfaces 3524 of the base 3520 to
move the
extensions 3552 inwardly towards each other. The inward motion of the
extensions 3552
causes the engagement surfaces 3549 to become disengaged from the second
surface 3574
of the spring retainer 3570, thereby allowing the rod 3540 to move between its
first
position to a second (or actuated) position.
[1160] The proximal
end portion 3542 of the rod 3540 includes a retention portion
3545 having a first surface 3547 and a second surface 3546. The first surface
3547 of the
retention portion 3545 engages the distal portion 3416 of the compressed gas
container
3412. The second surface 3546 of the retention portion 3545 engages a proximal
end
3562 of the spring 3560. Similarly, the first surface 3572 of the spring
retainer 3570
engages a distal end 3564 of the spring 3560. In this manner, when the rod
3540 is in its
34
Date Recue/Date Received 2021-02-19
first position, the spring 3560 can be compressed between the spring retainer
3570 and the
retention portion 3545 of the rod 3540. Accordingly, when the rod 3540 is
disengaged
from the spring retainer 3570, the force imparted by the spring 3560 on the
retention
portion 3545 of the rod 3540 causes the rod 3540 to move proximally into its
second
position.
[1161] The proximal end portion 3542 of the rod 3540 is coupled to the
compressed
gas container 3412 by a connector 3580, which is secured to the distal end
portion 3416 of
the compressed gas container 3412 by a securing member 3588. The connector
3580
includes a proximal end portion 3582 and a distal end portion 3584. The distal
end portion
3584 of the connector 3580 is disposed within the opening 3554 defined between
the
extensions 3552. In this manner, the connector 3580 is retained by the
proximal end
portion 3542 of the rod 3540. As will be described in more detail, the distal
end portion
3584 of the connector 3580 includes locking tabs 3587.
[1162] The proximal end portion 3582 of the connector 3580 includes
engagement
portions 3586 that engage the distal end portion 3416 of the compressed gas
container
3412. The engagement portions 3586 are coupled to the compressed gas container
3412
by the securing member 3588, which can be, for example, a shrink wrap, an
elastic band
or the like. In other embodiments, the engagement portions 3586 can produce an
interference fit with the compressed gas container 3412, thereby eliminating
the need for a
securing member 3588.
[1163] Because the rod 3540 is coupled to the compressed gas container
3412, when
the rod 3540 is moved from its first (engaged) position to its second
(actuated) position,
the compressed gas container 3412 is moved proximally within the housing 3110
into
engagement with the gas release mechanism 3612. FIG. 31 shows the auto-
injector in a
second configuration, in which the compressed gas container 3412 is engaged
with the gas
release mechanism 3612. When in the second configuration, the compressed gas
contained within the compressed gas container 3412 is released to actuate the
medicament
injector 3210. A more detailed description of the gas release process is
provided below
with reference to FIGS. 32 through 36.
[1164] FIG. 32 shows an exploded view of the system actuator 3510, the
compressed
gas container 3412 and the gas release mechanism 3612, each of which are
disposed
Date Recue/Date Received 2021-02-19
within the gas container opening 3124 defined by the housing 3110 (see FIG.
36). As
shown, the compressed gas container 3412, the system actuator 3510 and the gas
release
mechanism 3612 are arranged substantially coaxial with each other. As
previously
discussed, when the auto-injector 3002 is actuated, the compressed gas
container 3412 is
moved proximally within the gas container opening 3124 defined by the housing
3110, as
indicated by the arrow K in FIG. 32, until the proximal end 3414 of the
compressed gas
container 3412 engages the gas release mechanism 3612.
[1165] As shown in FIGS. 33 and 34, the gas release mechanism 3612 includes
a cap
3630 and a puncturing element 3620 coupled to and disposed within the cap
3630. The
puncturing element has a proximal end 3622 and a distal end 3624. The distal
end 3624 of
the puncturing element 3620 defines a sharp point 3626 configured to puncture
the
proximal end 3414 of the compressed gas container 3412. The puncturing element
3620
defines an opening 3627 extending from its distal end 3624 to its proximal end
3622.
[1166] The cap 3630 has a proximal end 3632, an outer surface 3635 and an
inner
surface 3636. The inner surface 3636 of the cap 3630 defines an opening 3634
that
receives the proximal end 3414 of the compressed gas container 3412 when the
auto-
injector 3002 is in its second configuration. The proximal end 3632 of the cap
3630
defines an opening 3638 therethrough and a channel 3640 in fluid communication
with the
opening 3638. The opening 3638 receives the proximal end 3622 of the
puncturing
element 3620 to couple the puncturing element 3620 to the cap 3630. The
puncturing
element 3620 is disposed within the cap 3630 such that when the compressed gas
container 3412 is moved into the opening 3634, the distal end 3624 of the
puncturing
element 3620 punctures the proximal end 3414 of the compressed gas container
3412.
[1167] The cap 3630 is disposed within the gas container opening 3124 such
that the
outer surface 3635 of the cap 3630 engages the inner surface 3123 of the
housing 3110. In
some embodiments, the outer surface 3635 of the cap 3630 can be sized to
produce an
interference fit with the inner surface 3123 of the housing 3110. In other
embodiments,
the cap 3630 can be fixedly coupled within the gas container opening 3124
using an
adhesive or any other suitable attachment mechanism.
[1168] The cap 3630 is oriented within the gas container opening 3124 so
that the
channel 3640 is aligned with and in fluid communication with the gas
passageway 3126
36
Date Recue/Date Received 2021-02-19
defined by the housing 3110. Moreover, when oriented in this manner, the
protrusion
3642 on the proximal end 3632 of the cap 3630 obstructs a portion of the gas
passageway
3126, which can be manufactured as a through-hole, to fluidically isolate the
gas
passageway 3126 from an area outside of the housing 3110. After the proximal
end 3414
of the compressed gas container 3412 has been punctured, pressurized gas flows
from the
compressed gas container 3412 into the gas passageway 3126 through the opening
3627
defined by the puncturing element 3620 and the channel 3640 defined by the
proximal end
3632 of the cap 3630.
[1169] The inner surface 3636 of the cap 3630 is configured to hermetically
seal the
proximal end 3414 of the compressed gas container 3412 within the opening
3638. This
arrangement prevents pressurized gas from leaking around the compressed gas
container
3412 to an area outside of the housing 3110 after the proximal end 3414 of the
compressed
gas container 3412 has been punctured. In some embodiments, the inner surface
3636 is
sized to produce an interference fit with the compressed gas container 3412.
In other
embodiments, the cap 3630 includes a separate sealing member, such as, for
example, an
o-ring, to seal the proximal end 3414 of the compressed gas container 3412
within the
opening 3638.
[1170] After the compressed gas container 3412 is moved into engagement
with the
gas release mechanism 3612, the position of the compressed gas container 3412
within the
gas container opening 3124 is maintained by the locking tabs 3587 on the
connector 3580.
As shown in FIG. 29, each locking tab 3587 includes a pointed portion that is
angled
outwardly from the connector 3580. This arrangement allows the connector 3580
to move
proximally within the gas container opening 3124 of the housing 3110, but
prevents the
connector 3580 from moving distally within the gas container opening 3124 of
the housing
3110. Said another way, the arrangement of the locking tabs 3587 prevents the
compressed gas container 3412 from being "kicked back" when exposed to the
force
produced by the pressurized gas as the pressurized gas is released.
[1171] As previously discussed, the pressurized gas released from the
compressed gas
container 3412 produces a force on the boundary of the gas chamber 3120,
including the
surface 3322 of the movable member 3312. This force causes the movable member
3312
and the medicament injector 3210 move together distally within the housing
3110, as
37
Date Recue/Date Received 2021-02-19
shown by arrow L, placing the auto-injector 3002 in a third configuration, as
shown in
FIG. 37. When in the third configuration, the distal end 3214 of the needle
3212 is
disposed through the opening 3532 defined by the base 3520 to an area outside
of the
auto-injector 3002. Moreover, as shown in FIG. 38, when the auto-injector 3002
is in the
third configuration, the proximal end 3216 of the needle 3212 remains spaced
apart from
the distal end 3266 of the medicament container 3210, ensuring that the needle
3212
remains fluidically isolated from the medicament container 3210. In this
manner, the
needle 3212 can be inserted into a patient as the auto-injector 3002 moves
between its
second configuration (FIG. 31) and its third configuration (FIG. 37) without
injecting the
medicament until after insertion is completed. A more detailed description of
the
medicament injector 3210 and the movable member 3312 is provided below with
reference to FIGS. 37 through 42.
[1172] As previously described, the medicament injector 3210 includes a
carrier 3250,
a medicament container 3262 and a needle 3212. The carrier 3250 has a lower
portion
3222 and an upper portion 3252. The lower portion 3222 of the carrier 3250
includes a
needle hub 3223, which contains the needle 3212. The lower portion 3222 of the
carrier
3250 also defines an opening 3224 configured to receive a distal portion 3266
the
medicament container 3262. As shown in FIG. 39, the needle 3212 is coupled to
the
needle hub 3223 such that the proximal end 3216 of the needle 3212 is disposed
within the
opening 3224 and the distal end 3214 of the needle 3212 extends distally
outside of the
needle hub 3223.
[1173] The inner surface 3228 of the lower portion 3222 defining the
opening 3224
includes a protrusion 3226. The protrusion 3226 is configured to engage a
corresponding
recess 3272 defined by a sealing cap 3270 disposed at the distal portion 3266
of the
medicament container 3262 (see FIG. 42) to secure the medicament container
3262 within
the opening 3224 such that the proximal end 3216 of the needle 3212 is spaced
apart from
the distal end 3266 of the medicament container 3210. The protrusion 3226 and
the recess
3272 are configured such that the protrusion 3226 will become disengaged from
the recess
3272 when the force applied exceeds a predetermined value. Said another way,
the
protrusion 3226 and the recess 3272 collectively form a removable snap-fit
that allows the
medicament container 3262 to be moved within the opening 3224 when the force
applied
to the medicament container 3262 exceeds a predetermined value. This
arrangement
38
Date Recue/Date Received 2021-02-19
ensures that the needle 3212 remains fluidically isolated from the medicament
container
3262 during the insertion operation.
[1174] The outer surface 3236 of the lower portion 3222 includes a
protrusion 3238.
As previously described, the protrusion 3238 is configured to engage a
corresponding
recess portion 3828 within the opening 3826 of the sheath 3820 (see FIG. 23)
to
removably couple the sheath 3820 to the needle hub 3223.
[1175] The lower portion 3222 of the carrier 3250 also defines two
retraction spring
pockets 3242 each receiving the proximal end 3352 of a retraction spring 3350.
As
previously discussed, the distal end 3354 of each retraction spring 3350 is
retained within
the retraction spring pockets 3531 defined by the base 3520. As shown in FIG.
38, when
the carrier 3250 moves distally within the housing 3110, the retraction
springs 3350 are
compressed and therefore bias the carrier 3250 towards the proximal portion
3112 of the
housing 3110.
[1176] The upper portion 3252 of the carrier 3250 defines an opening 3256
configured
to receive a proximal portion 3264 of the medicament container 3262 and
includes two
valve actuators 3254. As described in more detail herein, the valve actuators
3254 are
configured to engage a gas relief valve 3328 to allow the pressurized gas
contained within
the gas chamber 3120 to escape when the injection event is complete.
[1177] The upper portion 3252 of the carrier 3250 defines four gas relief
passageways
3258. Similarly, the lower portion 3222 of the carrier 3250 defines four gas
relief
passageways 3244. When the pressurized gas is released from the gas chamber
3120, the
gas relief passageways 3258, 3244 provide a fluid path to allow the
pressurized gas to
flow from the gas chamber 3120 to an area outside of the housing 3110.
[1178] As described above, the movable member 3312 includes a proximal end
portion 3316 and a distal end portion 3318. The distal end portion 3318
includes a piston
3324 disposed within the proximal portion 3264 of the medicament container
3262, such
that the piston engages a plunger 3284 contained within the medicament
container 3262,
as shown in FIG. 42.
39
Date Recue/Date Received 2021-02-19
[1179] The proximal end portion 3316 includes a surface 3322 that defines a
portion
of a boundary of the gas chamber 3120. As shown in FIG. 41, the proximal end
portion
3316 defines two openings 3326 therethrough, each of which are in fluid
communication
between the gas chamber 3120 and the interior of the housing 3110 outside the
gas
chamber 3120. The proximal end portion 3316 further defines a slot 3330 that
receives a
gas relief valve 3328, which can be, for example, a flexible rubber member.
The gas relief
valve 3328 is positioned within the slot 3330 and adjacent the openings 3326
to selectively
allow fluid communication between the gas chamber 3120 and the area outside
the gas
chamber 3120 through the openings 3326. The operation of the gas relief valve
3328 is
discussed in more detail herein.
[1180] The proximal end portion 3316 of the movable member 3312 also
includes a
seal 3314 that engages a portion the inner surface 3122 of the housing 3110
(see FIG. 36)
to fluidically isolate the gas chamber 3120. Although the seal 3314 is shown
as being an
o-ring seal, in some embodiments, the seal need not be a separate component,
but can
rather be a portion of the proximal end portion 3316 of the movable member
3312.
[1181] When the needle insertion operation is completed, the lower portion
3222 of
the carrier 3250 engages the base 3520, preventing further distal movement of
the carrier
3250 within the housing. Because the distal motion of the carrier 3250 is
opposed, the
force exerted by the pressurized gas on the surface 3322 of the movable member
3312
increases until the protrusion 3226 of the lower portion 3222 of the carrier
3250 and the
recess 3272 defined by sealing cap 3270 of the medicament container 3262
become
disengaged. Accordingly, the medicament container 3262 to moves distally
relative to the
carrier 3250, placing the auto-injector 3002 in a fourth configuration, as
shown in FIG. 43.
When moving between the third configuration (FIG. 38) and the fourth
configuration
(FIG. 43), the proximal end 3216 of the needle 3212 pierces the sealing cap
3270 and the
liner 3271 disposed at the distal portion 3266 of the medicament container
3262. As such,
when in the fourth configuration, the proximal end 3216 of the needle 3212 is
in fluid
communication with the medicament container 3262, thereby allowing the
medicament to
be injected.
[1182] Once the needle 3212 is in fluid communication with the medicament
container
3262, the force from the pressurized gas causes the piston 3324 of the movable
member
Date Recue/Date Received 2021-02-19
3312 to move the plunger 3284 within the medicament container 3262, as shown
by arrow
M, thereby expelling the medicament through the needle 3212. The piston 3324
and the
plunger 3284 move a predetermined distance within the medicament container
3262,
placing the auto-injector 3002 in a fifth configuration, as shown in FIG. 44.
When the
auto-injector 3002 is in the fifth configuration, the injection of medicament
is complete.
[1183] When the auto-injector 3002 is in its fifth configuration, proximal
portion 3316
of the movable member 3312 is in contact with the upper portion 3252 of the
carrier 3250,
thereby preventing further movement of the piston 3324 within the medicament
container
3262. In this manner, the distance through which the piston 3324 travels, and
therefore
the amount of medicament injected, can be controlled.
[1184] Additionally, when the auto-injector 3002 is in its fifth
configuration, the valve
actuators 3254 are disposed within the openings 3326 such that the valve
actuators 3254
displace the gas relief valve 3328. Accordingly, the pressurized gas contained
within the
gas chamber 3120 can flow from the gas chamber 3120 to the area within the
housing
3310 outside of the gas chamber 3310. As previously discussed, the gas relief
passageways 3258, 3244 provide a fluid path to allow the pressurized gas to
flow from the
gas chamber 3120, through the opening 3532 defined by the base 3520 and to an
area
outside of the housing 3110.
[1185] When the pressurized gas flows out of the gas chamber 3120, the
pressure
exerted on the surface 3322 of the movable member 3312 decreases. Accordingly,
the
force exerted by the retraction springs 3350 is sufficient to move the
medicament injector
3210 and the movable member 3312 proximally within the housing 3110, as shown
by
arrow N, into a sixth (or retracted) configuration as shown in FIG. 45.
Because the
medicament injector 3210 and the movable member 3312 move together, the valve
actuators 3254 remain disposed within the openings 3326 as the auto-injector
3002 moves
into the sixth configuration. In this manner, the gas relief valve 3328
remains displaced
and the openings 3326 remain in fluid communication with the gas chamber 3120
and the
area within the housing 3310 outside of the gas chamber 3310 independent of
the position
of the movable member 3312. Such an arrangement ensures that all of the
pressurized gas
flows out of the gas chamber 3120, thereby ensuring that the medicament
injector 3210
and the movable member 3312 return to the sixth configuration and do not
oscillate
41
Date Recue/Date Received 2021-02-19
between the sixth configuration and the fifth configuration, which could lead
to the needle
3212 not being fully retracted into the housing 3110.
[1186] Although the auto-injector 3002 has been shown and described having
a
housing 3110 having a substantially rectangular shape, in some embodiments, an
auto-
injector can have a housing having any shape. In some embodiments, for
example, an
auto-injector can have a substantially cylindrical shape. In other
embodiments, for
example, the auto-injector can have an irregular and/or asymmetrical shape.
[1187] Although the auto-injector 3002 has been shown and described as
including a
protrusion 3142 disposed at the distal end portion 3114 of the housing 3110 to
help a user
grasp and retain the housing 3110, in some embodiments, a protrusion can be
disposed
anywhere along the housing. In other embodiments, a protrusion can
symmetrically
surround the distal portion of the housing. In yet other embodiments, the
housing of an
auto-injector can include a gripping portion configured to help a user grasp
and retain the
housing. The gripping portion can include, for example, a textured surface, a
contoured
surface, a surface having an adhesive that forms a tacky surface to adhere to
the user's
hand or the like. For example, FIG. 46 shows an auto-injector 4002 according
to an
embodiment of the invention having a housing 4110. The housing 4110 includes a
proximal end portion 4112, a distal end portion 4114 and a gripping portion
4140. The
distal end portion 4114 of the housing 4110 includes a protrusion 4142 to
prevent the
user's hand from slipping off of the distal end portion 4114 of the housing
4110 when
using the auto-injector 4002. Similarly, the gripping portion 4140 includes a
series of
contours 4144 that engage the user's fingers to help the user grasp and retain
the housing
4110 when the auto-injector 4002 is in use.
[1188] The distal end portion 4114 of the housing 4110 also includes two
alignment
marks 4146 to guide the user when placing the auto-injector 4002 against the
body.
Although the alignment marks 4146 are shown as markings on the housing 4110,
in other
embodiments, the alignment marks can include protrusions, openings or the
like.
[1189] Certain components of the auto-injector 3002 are shown and described
as being
coupled together via protrusions and mating recesses. The protrusions and/or
recesses can
be disposed on any of the components to be coupled together and need not be
limited to
only a certain component. For example, the base 3520 is shown as defining two
openings
42
Date Recue/Date Received 2021-02-19
3536 that receive corresponding attachment protrusions 3150 on the distal end
portion
3114 of the housing 3110. In some embodiments, however, the protrusions can be
disposed on the base and the mating recesses can be defined by the distal end
portion of
the housing. In other embodiments, two or more components can be coupled
together in
any suitable way, which need not include protrusions and mating recesses. For
example,
in some embodiments, two or more components can be coupled together via mating
shoulders, clips, adhesive and the like.
[1190] Similarly, although certain components of the auto-injector 3002 are
shown
and described as being constructed from multiple separate components, in some
embodiments, such components can be monolithically constructed. For example,
the
carrier 3250 is shown and described as including an upper portion 3252 and a
lower
portion 3222 that are constructed separately and then coupled together. In
other
embodiments, a carrier can be constructed monolithically.
[1191] Although the sheath retainer 3840 of the auto-injector 3002 has been
shown
and described as including a protrusion 3856 that engages a corresponding
recess 3526 in
the base 3520 to removably couple the sheath retainer 3840 to the base 3520,
in some
embodiments, the sheath retainer can include a protrusion configured to engage
a different
corresponding recess on the auto-injector 3002. For example, the sheath
retainer can
include a protrusion configured to engage a corresponding recess in the distal
end portion
3114 of the housing 3110.
[1192] Although the safety lock (or locking member) 3710 of the auto-
injector 3002
has been shown and described as including a protrusion 3718 configured to
engage a base
3520 movably coupled to the housing 3110, in some embodiments, the safety lock
can
include a protrusion configured to engage a different portion of the auto-
injector 3002.
For example, the safety lock can include a protrusion configured to engage a
portion of the
housing 3110, such as the distal end portion 3114 of the housing 3110, to
removably
couple the safety lock in its first position.
[1193] Although the base 3520 of the auto-injector 3002 has been shown and
described covering almost the entire distal end portion 3114 of the housing
3110, in some
embodiments, a base configured to actuate the auto-injector can be disposed
about only a
portion of the distal end of the housing. For example, in some embodiments, an
auto-
43
Date Recue/Date Received 2021-02-19
injector can include a button extending from the distal end portion of the
housing
configured to engage and release the system actuator.
[1194] Although the rod 3540 is shown and described as being an elongated
member
that is released by being elastically deformed, in some embodiments, a rod can
be of any
suitable shape and in any suitable orientation within the housing. Moreover,
in some
embodiments, a rod can be released by being plastically deformed. For example,
in some
embodiments, a rod can be disposed along an axis that is offset from the
longitudinal axis
of the energy storage member. In some embodiments, the rod can be configured
to break
upon actuation.
[1195] Although the gas release mechanism 3612 is shown and described as
including
a puncturing element 3620 to puncture a portion of the compressed gas
container 3262, the
gas release mechanism 3612 need not include a puncturing element 3620. For
example, in
some embodiments, the gas release mechanism can include an actuator configured
to
actuate a valve that controls the flow of gas out of the compressed gas
container. For
example, in some embodiments, a compressed gas container can include a spring
loaded
check ball and the gas release mechanism can include an actuator configured to
engage
and depress the check ball to release pressurized gas from the compressed gas
container.
[1196] Although the distance through which the piston 3324 travels, and
therefore the
amount of medicament injected, is shown and described as being controlled by
configuring the movable member 3312 such that it is in contact with the upper
portion
3252 of the carrier 3250 when the auto-injector 3002 is in its fifth
configuration, in other
embodiments, any suitable method of controlling the piston travel can be
employed. For
example, in some embodiments, piston travel can be limited by including a
protrusion
within the medicament container, such as a necked portion, that limits the
motion of the
piston within the medicament container. In other embodiments, the housing can
include a
protrusion to limit the motion of the movable member. In yet other
embodiments, the
valve actuator can be configured to actuate the gas relief valve when the
piston has moved
a predetermined distance within the medicament container. In yet other
embodiments, a
combination of each of the above methods for controlling the piston travel can
be
employed.
44
Date Recue/Date Received 2021-02-19
[1197] Although the auto-injector 3002 is shown and described as having six
different
configurations that are different from each other, in some embodiments, a
certain
configuration of an auto-injector can be the same as another configuration.
For example,
in some embodiments, a "pre-actuation" configuration can be the same as a
"retracted"
configuration. In other embodiments, any of the functions described above can
be
accomplished when an auto-injector is moved between any number of different
configurations.
[1198] Although the auto-injector 3002 is shown and described as including
a
compressed gas cylinder 3412, in other embodiments an auto-injector can
include any
suitable energy storage member. For example, in some embodiments, an auto-
injector can
include a mechanical energy storage member, such as a spring, an electrical
energy storage
member, such as a battery or a capacitor, a chemical energy storage member,
such as a
container containing two substances that can react to produce energy, a
magnetic energy
storage member or the like. Similarly, although the auto-injector 3002 is
shown and
described as including a gas release mechanism 3612, in other embodiments an
auto-
injector can include any suitable energy release mechanism. Such energy
release
mechanism can include, for example, an electrical circuit, a mechanical spring
retainer, a
fluid control valve or the like.
[1199] For example, FIG. 47 shows a schematic illustration of an auto-
injector 5002
that includes a mechanical energy storage member 5410. The auto-injector 5002
includes
a housing 5110 that contains a medicament container 5262, an energy storage
member
5410, a release member 5540. The medicament container 5262 is movably disposed
within the housing 5110 and includes a needle 5212 through which a medicament
5268
can be injected. As illustrated, the medicament container 5262 can be moved
along its
longitudinal axis Lm between a first position (FIG. 47) and a second position
(not shown),
in which the needle 5212 extends from the housing 5110.
[1200] The energy storage member 5410 includes a spring 5420 that is
disposed about
a rod 5422. The rod 5422 has a proximal end 5424 and a distal end 5426. The
proximal
end 5424 of the rod 5422 includes a plunger 5428 that retains the spring 5420
such that the
spring 5420 can be compressed when the auto-injector 5002 is in a first
configuration.
The plunger is also disposed within a working fluid chamber 5430. The working
fluid
Date Recue/Date Received 2021-02-19
chamber 5430 can be, for example, a hydraulic cylinder filled with a hydraulic
fluid. The
distal end 5426 of the rod 5422 engages the release member 5540, as discussed
below.
[1201] In use, the spring 5420 can be moved within the housing 5110 along
its
longitudinal axis Le between a first position and a second position. When the
spring 5420
moves between its first position to its second position, the plunger 5428
moves proximally
within the working fluid chamber 5430, causing the working fluid 5431 to be
forced
through a valve 5434 and into contact with the medicament container 5262.
Through the
kinetic energy produced by the spring 5420, the working fluid 5431 produces a
force that
acts upon the medicament container 5262 to move the medicament container 5262
between its first position and its second position.
[1202] The arrangement of a mechanical energy storage member, such as a
spring, and
a fluidic circuit allows the direction and/or magnitude of the force produced
by the energy
storage member to be changed. In this manner, as shown in FIG. 47, the
longitudinal axis
Le of the energy storage member can be offset from the longitudinal axis Lm of
the
medicament container 5262, thereby allowing the medicament container 5262 and
the
energy storage member 5410 to be arranged within the housing 5110 in any
number of
different configurations.
[1203] The release member 5540 is disposed adjacent a distal end portion
5114 of the
housing 5110 and is configured to selectively deploy the spring 5420 from its
first position
to its second position. The release member 5540 can be any suitable mechanism
of the
types described above for moving the spring 5420. In this manner, a user can
actuate the
auto-injector by manipulating the distal end portion 5114 of the housing 5110.
[1204] FIG. 48 shows a schematic illustration of an auto-injector 6002 that
includes an
electrical energy storage member 6410, such as, for example a battery. The
auto-injector
6002 includes a housing 6110 that contains a medicament container 6262, an
energy
storage member 6410, a system actuator 6510 and an energy release mechanism
6610.
The medicament container 6262 is movably disposed within the housing 6110 and
includes a needle 6212 through which a medicament 6268 can be injected. As
illustrated,
the medicament container 6262 can be moved along its longitudinal axis Lm
between a
first position (FIG. 48) and a second position (not shown), in which the
needle 6212
extends from the housing 6110.
46
Date Recue/Date Received 2021-02-19
[1205] The energy storage member 6410 is also movably disposed within the
housing
6110 along its longitudinal axis Le, which is offset from the longitudinal
axis Lm of the
medicament container 6262. When the energy storage member 6410 is in its first
position
(FIG. 48), it is spaced apart from the electrical contact 6650 of the energy
release
mechanism 6610. When the energy storage member 6410 is in its second position,
it is in
contact with the electrical contact 6650, thereby allowing current to flow
from the energy
storage member 6410 to an actuator 6654 via a circuit 6652. The actuator 6654
converts
the electrical energy into a force that acts upon the medicament container
6262 to move
the medicament container 6262 between its first position and its second
position.
[1206] The system actuator 6510 includes a release member 6540 coupled to
the
energy storage member 6410, a spring 6560 and an actuator button 6520. The
spring 6560
is disposed about the release member 6540 in a compressed configuration. The
release
member 6540 is removably coupled to the actuator button 6520, which is
disposed at the
distal end of the housing 6110. When the actuator button 6520 is manipulated,
the release
member 6540 is de-coupled from the actuator button 6520, thereby allowing the
force
from the spring 6560 to move the release member 6540. In this manner, the
energy
storage member 6410 is moved proximally within the housing 6110 into its
second
configuration. In some embodiments, the components included in the system
actuator
6510 can be electrically coupled to the energy storage member 6410.
[1207] Although the auto-injectors shown and described include a medicament
container and an energy storage member that are substantially parallel, in
some
embodiments, the medicament container and the energy storage member can be
angularly
offset from each other. For example, FIGS. 49 and 50 are schematic
illustrations of an
auto-injector 7002 in a first configuration and a second configuration,
respectively.
Similar to the auto-injectors described above, the auto-injector 7002 includes
a housing
7110 that contains a medicament container 7262, an energy storage member 7410,
a
release member 7540 and an energy release mechanism 7610. The medicament
container
7262, which includes a needle 7212, is disposed within the housing such that
it can be
moved along its longitudinal axis Lm as indicated by arrow P between a first
position
(FIG. 49) and a second position (FIG. 50).
47
Date Recue/Date Received 2021-02-19
[1208] The energy storage member 7410 is also movably disposed within the
housing
7110 along its longitudinal axis Le, as shown by arrow Q. As shown, the
longitudinal axis
Le is substantially perpendicular to the longitudinal axis Lm of the
medicament container
7262. When the energy storage member 7410 is in its first position (FIG. 49),
it is spaced
apart from the energy release mechanism 7610. When the energy storage member
7410 is
in its second position (FIG. 50), it is in contact with the energy release
mechanism 7610,
thereby releasing energy to produce a force on the medicament container 7262
in a manner
as described above.
[1209] As described above, the release member 7540 can be any suitable
mechanism
configured to selectively deploy the energy storage member 7410 from its first
position to
its second position.
[1210] Although the auto-injectors shown and described above include a
medicament
container configured to move within the housing, in some embodiments, an auto-
injector
can be configured to move a needle within a stationary medicament container.
For
example, FIGS. 51 and 52 are schematic illustrations of an auto-injector 8002
in a first
configuration and a second configuration, respectively. The auto-injector 8002
includes a
housing 8110 that contains a medicament container 8262, a movable member 8312,
an
energy storage member 8410, an energy release mechanism 8610 and a release
member
8540. The medicament container 8262 is fixedly disposed within the housing and
defines
a longitudinal axis Lm.
[1211] The movable member 8312 includes a proximal end 8316 and a distal
end
8318. The distal end 8318 of the movable member 8312 is disposed within and
movable
within the medicament container 8262 along the longitudinal axis Lm, as shown
by the
arrow R. A needle 8212 is coupled to the distal end 8318 of the movable member
8312.
[1212] The energy storage member 8410 is also movably disposed within the
housing
8110 along its longitudinal axis Le, as shown by arrow S. As shown, the
longitudinal axis
Le is offset from the longitudinal axis Lm of the medicament container 8262.
When the
energy storage member 8410 is in its first position (FIG. 51), it is spaced
apart from the
energy release mechanism 8610. When the energy storage member 8410 is in its
second
position (FIG. 52), it is in contact with the energy release mechanism 8610,
thereby
producing a force on the proximal end 8316 of the movable member 8312. The
force
48
Date Recue/Date Received 2021-02-19
causes the movable member 8312 to be moved within the medicament container
8262. In
this manner, the needle 8212 is extended through the housing 8110 as the
medicament is
being injected.
[1213] As described above, the release member 8540 can be any suitable
mechanism
configured to selectively deploy the energy storage member 8410 from its first
position to
its second position.
[1214] Although the auto-injector 3002 is shown and described as including
a
compressed gas container 3412 disposed non-coaxially with a medicament
container 3262,
in some embodiments, an auto-injector can include a compressed gas container
that is
coaxial with a medicament container. For example, FIGS. 53-55 are schematic
illustrations of an auto-injector 9002 in a first configuration, a second
configuration, and a
third configuration, respectively. The auto-injector 9002 includes a housing
9110 that
contains a medicament container 9262, a movable member 9312, a compressed gas
container 9412 and a puncturer 9612. The medicament container 9262 is movably
disposed within the housing 9110 and includes a needle 9212 through which a
medicament
9268 can be injected. As illustrated, the medicament container 9262 can be
moved along
its longitudinal axis Lm between the first configuration (FIG. 53) and the
second
configuration (FIG. 54).
[1215] The compressed gas container 9412 is also movably disposed within
the
housing 9110 along its longitudinal axis Le, which is coaxial with the
longitudinal axis Lm
of the medicament container 9262. A biasing member 9560, such as, for example,
a
spring, is engaged with the compressed gas container 9412 to bias the
compressed gas
container 9412 distally towards the puncturer 9612. As shown in FIG. 53, when
the auto-
injector 9002 is in the first configuration, a retainer 9540 retains the
compressed gas
container 9412 in the proximal portion 9112 of the housing spaced apart from
the
puncturer 9612.
[1216] The movable member 9312 includes a proximal end portion 9316 and a
distal
end portion 9318. The proximal end portion 9316 includes a surface 9322 that,
together
with the housing 9110, defines a gas chamber 9120. The distal end portion 9318
is
disposed within the medicament container 9262. The movable member 9312 is
configured
49
Date Recue/Date Received 2021-02-19
to move the medicament container 9262 within the housing 9110 and inject the
medicament 9268.
[1217] In use, the auto-injector 9002 is actuated by manipulating the
proximal portion
9112 of the housing 9110 to move the retainer 9540, thereby allowing the
compressed gas
container 9412 to be moved distally until it engages the puncturer 9612, as
shown in FIG.
54. As described above, the puncturer 9612 punctures a portion of the
compressed gas
container 9412 thereby releasing the pressurized gas contained therein into
the gas
chamber 9120. The pressurized gas produces a force on the movable member 9312,
which
causes the movable member 9312 and the medicament container 9262 to move
distally
into the second configuration, as shown by the arrow T in FIG. 54. When in the
second
configuration, the needle 9212 is extended outside of the housing 9110. The
movable
member 9312 then continues to move distally within the medicament container
9262, as
shown by the arrow U in FIG. 55. In this manner, the medicament is injected
through the
needle 9212.
[1218] Although the auto-injectors are shown and described as being
actuated from the
distal end and including an energy storage member 3412 disposed non-coaxially
with a
medicament container 3262, in some embodiments, an auto-injector can be
actuated from
its distal end and include an energy storage member that is coaxial with a
medicament
container. For example, FIGS. 56 and 57 are schematic illustrations of an auto-
injector
10002 in a first and a second configuration, respectively. The auto-injector
10002
includes a housing 10110 that contains a medicament container 10262, an energy
storage
member 10410 and a system actuator 10510.
[1219] The medicament container 10262 defines a longitudinal axis Lm that
is coaxial
with a longitudinal axis of the energy storage member 10410. The medicament
container
10262 includes a needle 10212 through which a medicament can be injected. The
medicament container 10262 is movable within the housing along its
longitudinal axis Lm
between a first position (FIGS. 56 and 57) and a second position (not shown),
in which the
needle 10212 extends outside of the housing 10110. As described above, the
medicament
container 10262 is moved by a force produced by the energy storage member
10410.
[1220] The energy storage member 10410 is also movably disposed within the
housing
10110 along its longitudinal axis Le, as shown by arrow V in FIG. 57. When the
energy
Date Recue/Date Received 2021-02-19
storage member 10410 moves between a first position (FIG. 56) and a second
position
(FIG. 57), it produces a force on the medicament container 10262.
[1221] The system actuator 10510 includes a release member 10540 and an
actuator
button 10520. The release member 10540 is configured to selectively deploy the
energy
storage member 10410 from its first position to its second position. The
release member
10540 can be, for example, a spring-loaded rod, a retainer or the like. The
actuator button
10520 is coupled to the release member 10540 such that when the actuator
button 10520 is
manipulated, the release member 10540 can deploy the energy storage member
10410
from its first position to its second position. A portion of the actuator
button 10520
extends outside of the distal end portion 10114 of the housing 10110 such that
the user can
actuate the auto-injector 10002 by manipulating the distal end portion 10114
of the
housing 10110.
[1222] FIG. 58 shows a portion of a distally actuated system actuator 11510
according
to an embodiment of the invention. Similar to the system actuators shown and
described
above, the system actuator 11510 is configured to selectively move an energy
storage
member (not shown) into contact with an energy release mechanism (not shown).
The
system actuator 11510 includes a rod 11540, a spring 11560 and a spring
retainer 11570.
A proximal portion 11542 of the rod 11540 is coupled to the spring retainer
11570 by two
projections 11548, which can be moved inwardly towards each other to decouple
the rod
11540 from the spring retainer 11570, as previously discussed.
[1223] The spring 11560 is disposed about the rod 11540 in a compressed
state such
that the spring 11560 is retained by a distal end portion (not shown) of the
rod 11540 and
the spring retainer 11570. In this manner, the rod 11540 is spring-loaded,
similar to the
rod 3540 discussed above.
[1224] The system actuator 11510 also includes an actuator button 11520
that is
coupled via a flexible member 11525 to a pair of pivoting members 11523. A
portion of
the actuator button 11520 extends outside of the distal end portion of the
housing (not
shown). In use, the user can actuate the auto-injector by manipulating the
distal end
portion of the housing, for example, by pressing the actuator button 11520
inwardly as
indicated by the arrow W. The inward movement of the actuator button 11520
causes the
flexible member 11525, which can be, for example, a thin cable, to move as
indicated by
51
Date Recue/Date Received 2021-02-19
the arrow X. The movement of the flexible member 11525 causes the pivoting
members
11523 to pivot as indicated by the arrows Y, which then causes the projections
11548 to
move together, thereby releasing the rod 11540 from the spring retainer 11570.
[1225] Although the compressed gas container 3412 is shown and described
above as
a single-use compressed gas container disposed within the housing 3110, in
some
embodiments, a compressed gas container can be a multi-use container.
Moreover, the
compressed gas container need not be contained within the housing. For
example, in some
embodiments, the compressed gas container can be a container disposed outside
of the
housing. Additionally, the compressed gas container can be any source of
pressurized gas.
For example, in some embodiments, the compressed gas source can be a container
having
two or more chemicals formulated to produce a pressurized gas when mixed. In
other
embodiments, the compressed gas source can be any reservoir that can supply a
gas at
pressures greater than atmospheric pressure.
[1226] Although the auto-injectors shown and described above include a gas
relief
valve coupled to a movable member and configured to selectively allow fluid
flow through
an opening defined by the movable member, in some embodiments, the gas relief
valve
and/or the opening can be disposed apart from the movable member. For example,
FIGS.
59 ¨ 61 are schematic illustrations of an auto-injector 14002 in a first
configuration, a
second configuration and a third configuration, respectively. The auto-
injector 14002
includes a housing 14110, a medicament container 14262, a movable member
14312, a
gas relief valve 14328 and a compressed gas source 14412.
[1227] The medicament container 14262 is movably disposed within the
housing
14110 and defines a longitudinal axis Lm. An injection member 14212 is coupled
to and
can be placed in fluid communication with the medicament container 14262. The
injection member 14212 can be, for example, a needle, a nozzle or the like. As
illustrated,
the medicament container 14262 can be moved along its longitudinal axis Lm
between a
first position (FIG. 59) and a second position (FIG. 60). When the medicament
container
14262 is in its first (or retracted) position, the injection member 14212 is
disposed within
the housing 14110. When the medicament container 14262 is in the second (or
advanced)
position (FIG. 60), a portion of the injection member 14212 is disposed
outside of the
housing 14110 and is placed in fluid communication with the medicament
container
52
Date Recue/Date Received 2021-02-19
14262. In this manner, when the medicament container 14262 is in the second
(or
advanced) position, a medicament 14268 can be conveyed via the injection
member 14212
from the medicament container 14262 into a body of a patient. In some
embodiments, the
injection member 14212 is disposed adjacent an outer surface of the housing,
but can be
able to deliver a medicament into a body.
[1228] The movable member 14312 includes a proximal end portion 14316 and a
distal end portion 14318. As described above, the proximal end portion 14316
includes a
surface 14322 that, together with the housing 14110, defines a gas chamber
14120. The
proximal end portion 14316 also includes a seal 14314 that engages a portion
of the
housing to fluidically isolate the gas chamber 14120 from an area 14128 within
the
housing 14110. The distal end portion 14318 is disposed within and movable
within the
medicament container 14262 along the longitudinal axis Lm.
[1229] The housing 14110 includes a side wall 14122 that defines a portion
of the gas
chamber 14120. The side wall 14122 defines an opening 14152, which can be in
fluid
communication between the gas chamber 14120 and an area outside of the housing
14129.
The gas relief valve 14328 is coupled to the housing 14110 such that it can
selectively
allow fluid communication between the gas chamber 14120 and the area outside
of the
housing 14129 through the opening 14152.
[1230] Similar to the operation described above, when the auto-injector
14002 is
actuated, a pressurized gas flows from the compressed gas source 14412 into
the gas
chamber 14120. In response to a force produced by the pressurized gas, the
movable
member 14312 moves within the housing 14110 thereby placing the medicament
container
14262 in its second position (FIG. 60). The movable member 14312 continues to
move
within the medicament container 14262, as indicated by arrow P in FIG. 61, to
expel a
medicament 14268 through the injection member 14212. When the medicament
container
14262 is in is second position, the gas relief valve 14328 is actuated as
indicated by the
arrow Q in FIG. 61, thereby allowing pressurized gas to flow from the gas
chamber 14120
to the area outside of the housing 14129 through the opening 14152. The gas
relief valve
14328 can be actuated by any suitable valve actuator. For example, in some
embodiments
the auto-injector 14002 can include a mechanical valve actuator (not shown)
that the user
manually depresses to actuate the valve 14328.
53
Date Recue/Date Received 2021-02-19
[1231] FIGS. 62 and 63 are schematic illustrations of an auto-injector
15002 in a first
configuration and a second configuration, respectively. The auto-injector
15002 includes
a housing 15110, a medicament container 15262, a movable member 15312, a
compressed
gas source 15412 and a gas release assembly 15325. As described above, the
medicament
container 15262 is fixedly disposed within the housing 15110 and defines a
longitudinal
axis Lm.
[1232] The movable member 15312 includes a proximal end portion 15316 and a
distal end portion 15318. The proximal end portion 15316 includes a surface
15322 that
defines a portion of a boundary of a gas chamber 15120. The distal end portion
15318 is
movably disposed within the medicament container 15262 along the longitudinal
axis Lm,
as shown by the arrow S. A needle 15212 defining a lumen and a side opening
(not
shown) is coupled to the distal end 15318 of the movable member 15312.
[1233] The gas release assembly 15325 includes a gas relief valve 15328, a
flexible
member 15329 and an opening 15152. The opening 15152 is defined by a side wall
15122
of the housing 15110 that defines a portion of the gas chamber 15120. In this
manner, the
opening 15152 can provide fluid communication between the gas chamber 15120
and an
area outside of the housing 15129. The housing 15110 includes a covering
portion 15154
disposed adjacent the opening 15152 to prevent the opening 15152 from becoming
obstructed, to prevent the gas relief valve 15328 from being inadvertently
actuated or the
like.
[1234] The gas relief valve 15328 is removably disposed within the opening
15152
and has a first configuration (FIG. 62) and a second configuration (FIG. 63).
When the
gas relief valve 15328 is in its first configuration, it is disposed within
the opening 15152
such that it fluidically isolates the gas chamber 15120 from the area outside
of the housing
15129. When the gas relief valve 15328 is in its second configuration, it is
removed from
the opening 15152, thereby placing the gas chamber 15120 in fluid
communication with
the area outside of the housing 15129. The gas relief valve 15328 can be, for
example, a
rigid member that is press fit within the opening 15152, a flexible member
that is secured
about the opening 15152 by an adhesive, a frangible sealing member or any
other suitable
device that can be removably disposed within and/or about the opening 15152.
54
Date Recue/Date Received 2021-02-19
[1235] The gas relief valve 15328 is coupled to the movable member 15312 by
a
flexible member 15329. By coupling the gas relief valve 15328 to the movable
member
15312, the gas relief valve 15328 can be moved from its first configuration to
its second
configuration when the movable member 15312 reaches a predetermined position
within
the housing 15110. Moreover, after the gas relief valve 15328 has been
actuated, this
arrangement allows the gas relief valve 15328 to remain in its second
configuration
independent of the position of the movable member 15312. The flexible member
15329
can be any suitable structure for coupling the gas relief valve 15328 to the
movable
member 15312. For example, the flexible member can be a string, an elastic
member, a
biasing member or the like.
[1236] In use, when the auto-injector 15002 is actuated, a pressurized gas
flows from
the compressed gas source 15412 into the gas chamber 15120. In response to a
force
produced by the pressurized gas, the movable member 15312 moves within the
housing
15110 and the medicament container 15262. As a result, the needle 15212 is
extended
through the housing 15110 and the medicament is injected via the needle 15212.
When
the movable member 15312 reaches a predetermined position within the housing
15110,
the flexible member 15329 moves the gas relief valve 15328 into its second
configuration,
as shown by the arrow T in FIG. 63. In this manner, pressurized gas flows from
the gas
chamber 15120 to the area outside of the housing 15129 through the opening
15152, as
shown by the arrows g. As the pressure in the gas chamber 15120 is reduced,
the movable
member 15312 and the needle 15212 can be retracted into the housing 15110, as
described
above.
[1237] Although the auto-injector 3002 is shown and described as including
a gas
relief valve 3328 that is automatically actuated by a valve actuator 3254
disposed on the
carrier 3250, in some embodiments, an auto-injector can include a gas relief
valve that is
automatically actuated by any type of valve actuator. For example, in some
embodiments,
an auto-injector can include a gas relief valve that is actuated
electronically, magnetically,
hydraulically, pneumatically or by any other suitable mechanism. In other
embodiments,
an auto-injector can include a gas relief valve that is manually actuated by
the user, for
example, by a push button that extends within the housing.
Date Recue/Date Received 2021-02-19
[1238] Although the auto-injector 3002 shown and described above includes
an valve
actuator 3254 coupled to the carrier 3250, in some embodiments, an auto-
injector can
include a valve actuator disposed anywhere within the auto-injector. For
example, FIGS.
64 ¨ 66 are schematic illustrations of an auto-injector 16002 in a first
configuration, a
second configuration and a third configuration, respectively, in which a valve
actuator
16254 is coupled to a housing 16110. The auto-injector 16002 includes the
housing
16110, a medicament container 16262, a movable member 16312, a gas relief
valve
16328, the valve actuator 16254 and a compressed gas source 16412. As
described above,
the medicament container 16262 is fixedly disposed within the housing 16110
and defines
a longitudinal axis Lm.
[1239] The movable member 16312 includes a proximal end portion 16316 and a
distal end portion 16318. The proximal end portion 16316 includes a surface
16322 that
defines a portion of a boundary of a gas chamber 16120. The proximal end
portion 16316
defines an opening 16326 therethrough, which can be selectively placed in
fluid
communication between the gas chamber 16120 and an area outside of the gas
chamber
16128. The distal end portion 16318 is movably disposed within the medicament
container 16262 along the longitudinal axis Lm, as shown by the arrow U. A
needle
16212 defining a lumen and a side opening (not shown) is coupled to the distal
end 16318
of the movable member 16312.
[1240] A biasing member 16350 extends between the proximal end portion
16316 of
the movable member 16312 and the housing 16110. The biasing member, which can
be,
for example, a spring, an elastic member or the like, is configured to bias
the movable
member 16312 towards the proximal portion 16112 of the housing 16110.
[1241] The gas relief valve 16328 is coupled to the movable member 16312
adjacent
the opening 16326 and has a first configuration (FIG. 64) and a second
configuration
(FIGS. 65-66). When the gas relief valve 16328 is in its first configuration,
it is disposed
within the opening 16326 such that it fluidically isolates the gas chamber
16120 from the
area outside of the gas chamber 16128. When the gas relief valve 16328 is in
its second
configuration, it is moved or punctured, thereby placing the gas chamber 16120
in fluid
communication with the area outside of the gas chamber 16128.
56
Date Recue/Date Received 2021-02-19
[1242] The valve actuator 16254 has a proximal end 16253 and a distal end
16255 and
defines a lumen therethrough (not shown). The proximal end 16253 of the valve
actuator
16254 is configured to move or puncture the gas relief valve 16328 to move the
gas relief
valve 16328 between its first configuration and its second configuration. The
distal end
16255 of the valve actuator 16254 is coupled to the housing 16110. In use,
when the auto-
injector 16002 is actuated, the gas chamber 16120 is placed in fluid
communication with
the compressed gas source 16412, thereby allowing a pressurized gas to flow
into the gas
chamber 16120. The force produced by the pressurized gas on the surface 16322
of the
movable member 16312 causes the movable member 16312 to move within the
housing
16110 and the medicament container 16262, as shown in FIG. 65. As a result,
the needle
16212 is extended through the housing 16110 and the medicament is injected via
the
needle 16212.
[1243] When the movable member 16312 reaches a predetermined position
within the
housing 16110, the proximal end 16253 of the valve actuator 16254 punctures
the gas
relief valve 16328, thereby causing the gas relief valve 16328 to move
irreversibly into its
second configuration. In this manner, pressurized gas flows from the gas
chamber 16120
to the area outside of the gas chamber 16128 through the opening 16326, as
shown by the
arrows g. The pressurized gas also flows from the area outside of the gas
chamber 16128
to an area outside of the housing 16129 through the lumen defined by the valve
actuator
16254. In this manner, the valve actuator 16254 defines a portion of the gas
release path.
[1244] As shown in FIG. 66, when the pressurized gas flows out of the gas
chamber
16120, the pressure exerted on the surface 16322 of the movable member 16312
decreases. Accordingly, the force exerted by the biasing member 16350 is
sufficient to
move the movable member 16312 proximally within the housing 16110, as
indicated by
arrow V, such that the needle 16212 is retracted into the housing 16110.
Because the gas
relief valve 16328 remains in its second configuration during retraction, the
opening
16326 remains in fluid communication with the gas chamber 16120 and the area
outside of
the gas chamber 16128 independent of the position of the movable member 16312.
[1245] Additionally, the arrangement of the valve actuator 16254 can
control the
distance through which the movable member 16312 moves within the medicament
container 16262 (i.e., the stroke of the movable member), and therefore the
amount of
57
Date Recue/Date Received 2021-02-19
medicament injected. As shown in FIG. 64, the stroke of the movable member
16312 is a
function of the distance between the length L 1 of the valve actuator 16254
and the length
L2 of the movable member 16312 in its initial position. Accordingly, the
stroke of the
movable member 16312 can be controlled by varying the length Li of the valve
actuator
16254 and/or the length L2 of the movable member 16312 in its initial
position.
[1246] The proximal end portion 16316 and the distal end portion 16318 are
shown in
FIGS. 64 ¨ 66 as being separate components that are coupled together to form
the movable
member 16312. Such construction allows flexibility during manufacturing. For
example,
in some embodiments, the medicament container 16262 and the distal end portion
16318
are assembled in a sterile environment and later coupled to the proximal end
portion
16316 in a non-sterile environment. In other embodiments, the two-piece
arrangement of
the movable member 16312 provides flexibility in setting the length L2. For
example,
when a greater dosage of medicament is required, a shim or spacer (not shown)
can be
placed in the assembly joint between the proximal end portion 16316 and the
distal end
portion 16318 to increase the length L2.
[1247] Although the stroke of the movable member 16312, and therefore the
amount
of medicament injected, is shown and described as being controlled by
configuring the
valve actuator 16254 to actuate the gas relief valve 16328 when the movable
member
16312 has moved a predetermined distance within the medicament container
16262, in
other embodiments, any suitable mechanism for controlling the stroke of the
movable
member can be used. For example, the auto-injector 3002 shown and described
above is
configured so that the movable member 3312 contacts the carrier 3250 to limit
the stroke
of the movable member 3312. In other embodiments, the stroke of the movable
member
can be limited by including a protrusion within the medicament container, such
as a
necked portion, that limits the motion of the piston within the medicament
container. Tn
other embodiments, the housing can include a protrusion to limit the stroke of
the movable
member. In yet other embodiments, a combination of each of the above methods
for
controlling the stroke of the movable member can be employed.
[1248] As discussed above, the valve actuator need not mechanically actuate
the gas
relief valve. For example, FIGS. 67 and 68 are schematic illustrations of a
portion of an
auto-injector 17002 having a pneumatically actuated gas relief valve 17328.
Because the
58
Date Recue/Date Received 2021-02-19
auto-injector 17002 is similar to the auto-injectors described above, only the
gas relief
mechanism is discussed in detail. The auto-injector 17002 includes a housing
17110, a
movable member 17312 and a gas relief valve 17328. As described above, the
movable
member 17312 includes a proximal end portion 17316 that includes a surface
17322 that
defines a portion of a boundary of a gas chamber 17120. The proximal end
portion 17316
also includes a seal 17314 that engages a portion the housing 17110 to
fluidically isolate
the gas chamber 17120.
[1249] The housing 17110 includes a side wall 17122 that defines a portion
of the gas
chamber 17120. The side wall 17122 defines a first passageway 17152, which can
be
selectively placed in fluid communication between the gas chamber 17120 and an
area
outside of the housing 17129. The first passageway 17152 includes an opening
17153 into
the gas chamber 17120 that is defined proximal to the movable member 17312.
The side
wall 17122 defines a second passageway 17156 that is substantially parallel to
the side
wall 17122 and intersects the first passageway 17152. The second passageway
17156
includes an opening 17157 selectively disposable within the gas chamber 17120
depending on the position of the movable member 17312. The opening 17157 is
defined
distally from the opening 17153.
[1250] The gas relief valve 17328 includes a valve body 17360, a spring
17368 and a
spring retainer 17370. The valve body 17360 is movably disposed within the
second
passageway 17156 and has a first position (FIG. 67) and a second position
(FIG. 68). The
spring retainer 17370 is disposed within the second passageway 17156 and
engages one
end of the spring 17368. The second end of the spring 17368 engages a proximal
end
portion 17362 of the valve body 17360. In this manner, the valve body 17360 is
biased in
its first position, such that a distal end portion 17364 of the valve body
17360 engages a
shoulder 17158 defined by the second passageway 17156.
[1251] When the valve body 17360 is in its first position, the valve body
17360
obstructs the first passageway 17152, thereby fluidically isolating the gas
chamber 17120
from the area outside of the housing 17129. As the movable member 17312 moves
distally within the housing 17110, as shown by arrow W, the seal 17314
uncovers the
opening 17157 of the second passageway 17156. This allows pressurized gas from
the gas
chamber 17120 to flow into the second passageway 17156 and exert a force on
the distal
59
Date Recue/Date Received 2021-02-19
end portion 17364 of the valve body 17360. When force produced by the
pressurized gas
exceeds the force produced by the spring 17368, the valve body 17360 moves
proximally
within the second passageway 17156, as shown by arrow X. In this manner, the
opening
17153 of the first passageway 17152 is uncovered, thereby allowing fluid
communication
between the gas chamber 17120 and the area outside of the housing 17129.
[1252] The proximal
end portion 17362 of the valve body 17360 includes a projection
17366 designed to engage the spring retainer 17370 thereby maintaining the
valve body
17360 in its second position. Accordingly, when the movable member 17312 moves
proximally within the housing 17110 (i.e., the retraction operation) and the
opening 17157
is covered by the seal 17314, the valve body 17360 will not return to its
first
configuration. In this manner, the gas chamber 17120 remains in fluid
communication
with the area outside of the housing 17129 regardless of the position of the
movable
member 17312, thereby ensuring that the gas chamber 17120 is fully exhausted.
[1253] Although the
auto-injectors shown and described above include a gas relief
valve having a first configuration in which the gas chamber is fluidically
isolated and a
second configuration in which the gas chamber is in fluid communication with
an area
outside the gas chamber, in some embodiments, an auto-injector can include a
gas relief
valve having more than two configurations. For example, in some
configurations, an auto-
injector can include a gas relief valve having a fully closed configuration, a
fully opened
configuration and a partially opened configuration. In this manner, the gas
relief valve can
be used to regulate the pressure within the gas chamber and/or the flow of the
pressurized
gas from the gas chamber. Such regulation can be tailored to optimize the
needle insertion
and/or the medicament injection operations (i.e., to ensure that the needle
insertion is as
painless as possible, that the medicament absorption profile is optimal,
etc.).
[1254] Although the
auto-injectors shown and described above include a gas relief
valve that irreversibly changes from a first configuration in which the gas
chamber is
fluidically isolated to a second configuration in which the gas chamber is in
fluid
communication with an area outside the gas chamber, in some embodiments an
auto-
injector can include a gas relief valve configured to irreversibly change
between the first
configuration and the second configuration throughout the insertion and/or
injection cycle.
For example, in some embodiments, an auto-injector can include a gas relief
valve that
Date Recue/Date Received 2021-02-19
repeatedly cycles between its fully opened and its fully closed configurations
during a
single injection event. Such an arrangement also allows the gas relief valve
to be used to
regulate the pressure within the gas chamber and/or the flow of the
pressurized gas from
the gas chamber.
[1255] FIG. 69 is a schematic illustration of an auto-injector 18002 in
which the gas
relief valve 18328 has multiple different configurations, the gas relief valve
18328 being
shown in a first configuration. FIGS. 70 ¨ 73 are schematic illustrations of a
portion of the
auto-injector 18002 in which the gas relief valve 18328 is in a second through
a fifth
configuration, respectively. Because the auto-injector 18002 is similar to the
auto-
injectors described above, only the gas relief mechanism is discussed in
detail.
[1256] The auto-injector 18002 includes a housing 18110, a movable member
18312,
a medicament container 18262 and a gas relief valve 18328. The medicament
container
18262 is movably disposed within the housing 18110 and defines a longitudinal
axis Lm.
A needle 18212 is coupled to and can be placed in fluid communication with the
medicament container 18262. As described above, the medicament container 18262
can
be moved along its longitudinal axis Lm between a first position (FIG. 69) and
a second
position. When the medicament container 18262 is in its first (or retracted)
position, the
needle 18212 is disposed within the housing 18110. When the medicament
container
18262 is in the second position, at least a portion of the needle 18212
extends outside of
the housing 18110.
[1257] The movable member 18312 includes a proximal end portion 18316 and a
distal end portion 18318. As described above, the proximal end portion 18316
includes a
surface 18322 that, together with the housing 18110, defines a gas chamber
18120. The
proximal end portion 18316 also defines an opening 18326 therethrough, which
can be
selectively placed in fluid communication with the gas chamber 18120 and an
area outside
of the gas chamber 18128. The distal end portion 18318 is movably disposed
within the
medicament container 18262.
[1258] The gas relief valve 18328 includes a frangible seal 18361 and a
valve body
18360. The frangible seal 18361 is coupled to the movable member 18312
adjacent the
opening 18326. When the gas relief valve 18328 is in its first configuration
(FIG. 69) the
frangible seal 18361 fluidically isolates the gas chamber 18120 from the area
outside of
61
Date Recue/Date Received 2021-02-19
the gas chamber 18128. When gas relief valve 18328 is in its second through
fifth
configurations (FIGS. 70 ¨ 73), the frangible seal 18361 is moved or
punctured, which as
described below, can allow fluid communication between the gas chamber 18120
and the
area outside the gas chamber 18128 via the opening 18326. The valve body 18360
is
coupled to the housing 18110 and is configured to be disposed within the
opening 18326
when the movable member 18312 moves distally within the housing 18110. The
valve
body includes a first portion 18362, a second portion 18364, a third portion
18366 and a
fourth portion 18367.
[1259] The operation of the auto-injector 18002 and the various
configurations of the
gas relief valve 18128 are discussed with reference to FIG. 74, which shows a
plot of the
pressure within the gas chamber 18120 as a function of the position of the
movable
member 18312. In FIG. 74, the position of the movable member 18312, which also
corresponds to the configuration of the gas relief valve, is represented on
the x-axis. The
pressure within the gas chamber 18120 is represented on the y-axis.
[1260] In use, when the auto-injector 18002 is actuated, a pressurized gas
flows from a
compressed gas source 18412 (see FIG. 69) into the gas chamber 18120, causing
the
movable member 18312 to move distally within the housing. The movable member
18312
moves the medicament container 18262 between its first and its second position
(the
"needle insertion" operation). The needle insertion operation is shown in FIG.
74 as
region AA. As shown in FIG. 70, towards the end of the needle insertion
operation, the
movable member 18312 is positioned such that the first portion 18362 of the
valve body
18360 moves or punctures the frangible seal 18361, thereby placing the gas
relief valve
18128 in its second configuration (point CC on the plot in FIG. 74). When the
gas relief
valve is in its second configuration, the gas chamber 18120 is in fluid
communication with
the area outside the gas chamber 18128 via the opening 18326. Accordingly, the
pressure
within the gas chamber 18120 is reduced, as indicated in FIG. 74. Reducing the
pressure
during the needle insertion operation can, for example, reduce patient
discomfort during
the needle insertion operation.
[1261] When the medicament container 18262 reaches its second position, the
movable member 18312 continues to move distally within the medicament
container
18262, as shown by arrow Y, to inject the medicament through the needle 18212.
The
62
Date Recue/Date Received 2021-02-19
medicament injection operation is shown in FIG. 74 as region BB. As shown in
FIG. 71,
during the beginning of the injection operation, the movable member 18312 is
positioned
such that the second portion 18364 of the valve body 18360 is disposed within
the opening
18326, placing the gas relief valve 18128 in its third configuration (point DD
on the plot in
FIG. 74). The second portion 18364 of the valve body 18360 is configured to
fit within
the opening 18326 such that the gas chamber 18120 is substantially fluidically
isolated
from the area outside of the gas chamber 18128. Because pressurized gas
continues to
flow from the compressed gas source (not shown) into the gas chamber 18120, by
fluidically isolating the gas chamber 18120, the pressure within the gas
chamber 18120
will no longer decrease, but will instead remain constant or increase
slightly.
[1262] During the middle portion of the injection operation, the movable
member
18312 is positioned such that the third portion 18366 of the valve body 18360
is disposed
within the opening 18326, placing the gas relief valve 18128 in its fourth
configuration
(point EE on the plot in FIG. 74). The third portion 18366 of the valve body
18360 is
shaped to allow a controlled amount of pressurized gas to flow from the gas
chamber
18120 to the area outside the gas chamber 18128 via the opening 18326. Said
another
way, the third portion 18366 of the valve body 18360 and the opening 18326
define a flow
passageway between the gas chamber 18120 and the an area outside the gas
chamber
18128. The flow passageway varies based on the shape of the third portion
18366 of the
valve body 18360. For example, a narrow shaped third portion 18364 results in
a larger
flow area, whereas a larger shaped third portion 18366 results in a smaller
flow area. In
this manner, the flow area can be varied as a function of a longitudinal
position of the
movable member 18312. The third portion 18366 can be shaped such that the
pressurized
gas entering the gas chamber 18120 from the compressed gas source (not shown)
is equal
to the pressurized gas exiting the gas chamber 18120. Accordingly, as shown in
FIG. 74,
the pressure within the gas chamber 18120 can be substantially constant
throughout the
injection operation.
[1263] At the end of the injection operation, the movable member 18312 is
positioned
such that the fourth portion 18367 of the valve body 18360 is disposed within
the opening
18326, placing the gas relief valve 18128 in its fifth configuration (point FF
on the plot in
FIG. 74). The fourth portion 18367 of the valve body 18360 is considerably
smaller than
the third portion 18366, thereby allowing a significant amount of pressurized
gas to flow
63
Date Recue/Date Received 2021-02-19
from the gas chamber 18120 to the area outside the gas chamber 18128 via the
opening
18326. Said another way, when the fourth portion 18367 of the valve body 18360
is
within the opening 18326, the valve 18128 is "fully opened." Accordingly, as
shown in
FIG. 74, the pressure within the gas chamber 18120 decreases rapidly. In some
embodiments, the rapid drop in pressure allows the movable member 18312 to be
retracted
by a biasing member. In this manner, the needle 18212 is also retracted into
the housing
18110, thereby minimizing post-injection hazards.
[1264] Although the gas relief valve 18128 is described as being a
mechanical
component that varies a flow area as a function of the movable member, in
other
embodiments, the gas relief valve can be any suitable type of variable area
valve. For
example, in some embodiments, a gas relief valve can be an electrically
operated spool
valve.
[1265] While the valve body 18360 is shown as having four distinct regions
corresponding to four variably functional positions, in other embodiments, the
valve body
can have fewer or greater distinct regions corresponding to a different number
of
functional positions. Additionally, the shapes and sizes of the illustrated
valve body
portions 18362, 18364, 18366 and 18367 are shown by way of example only. In
some
embodiments, the valve body can be shaped according to a desired pressure
and/or
injection profile.
[1266] Although the auto-injectors are shown and described above as having
a single
gas chamber and a single gas relief valve, in some embodiments, an auto-
injector can
include any number of gas chambers and/or gas relief valves. For example, in
some
embodiments, an auto-injector can include a compressed gas source, an
auxiliary gas
chamber and a primary gas chamber. In a similar manner as described above, the
compressed gas source can be selectively placed in fluid communication with
the auxiliary
gas chamber, thereby allowing the auxiliary gas chamber to be filled with a
pressurized
gas. The auto-injector can include a first gas relief valve configured to
selectively place
the auxiliary gas chamber in fluid communication with the primary gas chamber.
When
pressurized gas is conveyed from the auxiliary gas chamber into the primary
gas chamber
via the first gas relief valve, the gas pressure within the primary gas
chamber causes an
injection event, as described above. The auto-injector can also include a
second gas relief
64
Date Recue/Date Received 2021-02-19
valve configured to selectively place the primary gas chamber in fluid
communication
with an area outside of the auto-injector housing. By including an auxiliary
gas chamber,
which can be vented independently from the primary gas chamber, the auto-
injector can be
configured as a multiple-use injector.
[1267] Similarly, while the auto-injectors are shown and described above as
having an
area outside of the gas chamber that is in fluid communication with an area
outside of the
housing, in some embodiments, the area outside of the gas chamber need not be
vented to
the atmosphere. For example, in some embodiments, an auto-injector can include
an area
outside of the gas chamber that is in fluid communication with a secondary gas
chamber.
[1268] Although the needle guard auto-injector 3002 is illustrated and
described above
as including a needle guard that covers or is disposed on a portion of the
distal end 3114 of
the housing 3110, in some embodiments, an auto-injector 3004 includes a
housing 3140
and a needle guard 3812 removably coupled to the distal end portion 3144 of
the housing
3140, as illustrated in FIGS. 75 - 76. The needle guard 3812 includes a sheath
3111 and a
sheath retaining portion 3113. The needle guard 3812 has a first position and
a second
position. In its first position, the needle guard 3812 is coupled to the
housing 3140. For
example, the sheath retaining portion 3113 of the needle guard 3812 is
configured to
substantially cover or encase the distal end portion 3144 of the housing 3140
when the
needle guard is in its first position. In its second position, the needle
guard 3812 is
removed from the housing 3140. The sheath 3111 is coupled to the sheath
retaining
portion 3113 similar to the coupling of the sheath 3820 and sheath retainer
3840 as
described in detail above with reference to FIG. 22. As such, as the sheath
retaining
portion 3113 is moved distally in the direction of arrow P, the sheath 3111 is
also moved
distally and removed from the housing 3140. Once the needle guard 3812 is
moved to its
second (or removed) position, the safety lock 3730 is accessible. The safety
lock 3730 is
removed from the housing 3140 by pulling the safety lock in a direction that
is
substantially normal to the direction in which the needle guard 3812 is
removed, such as in
the direction of arrow Q as illustrated in FIG. 76.
[1269] In some embodiments, as illustrated in FIGS. 77 ¨ 79, an auto-
injector 3006
includes a housing 3116, a safety guard 3130, and a distal end cap 3160. The
distal end
cap 3160 is configured to selectively engage or be coupled to the housing
3116. The distal
Date Recue/Date Received 2021-02-19
end cap 3160 prevents inadvertent actuation of the auto-injector 3006 by
substantially
covering at least a portion of the safety guard 3130 when the distal end cap
3160 is
engaged with or coupled to the housing 3116.
[1270] The distal end cap 3160 has a first position and a second position.
In its first
position, illustrated in FIG. 77, the distal end cap 3160 is removably coupled
to or engaged
with the distal end portion 3156 of the housing 3116. In its second position,
illustrated in
FIG. 78, the distal end cap 3160 is removed from the housing 3116. The distal
end cap
3160 must be removed from the auto-injector 3006 before the auto-injector can
be enabled
for use, thus preventing inadvertent actuation of the device. Furthermore, the
distal end
cap 3160 provides an additional barrier to contamination of the needle and the
medicament
disposed therein. The distal end cap 3160 can have a series of ridges or other
tactile
mechanism for assisting a user in gripping and/or removing the distal end cap.
The distal
end cap 3160 is replaceable. As such, if the distal end cap 3160 is removed
before a user
intends to use the auto-injector 3006, the user can put the distal end cap
back in its first
position without actuating or jeopardizing the sterility of the device.
[1271] Once the distal end cap 3160 is removed, the safety guard 3130 is
exposed and
can be removed. With the safety guard 3130 in place, the auto-injector 3006
can not be
actuated. The safety guard 3130, illustrated in FIGS. 80 ¨ 81, includes a base
portion
3132, a locking portion 3134, and a needle guard portion 3136. The locking
portion 3134
and needle guard portion 3136 extend proximally from the base portion 3132.
The base
includes a first end 3146 and a second end 3148. The locking portion 3134 is
disposed
adjacent the first end 3146 and includes a first engagement portion 3128. A
second
engagement portion 3138 is disposed adjacent the second end 3148 of the base
portion
3132.
[1272] The needle guard portion 3136 of the safety guard 3130 includes a
sheath 3152
and a sheath retaining portion 3154. The sheath 3152, which is similar to
sheath 3820
discussed in detail above, defines an opening configured to receive at least a
portion of a
needle of the auto-injector and is removably coupled to the sheath retaining
portion 3154.
The sheath retaining portion 3154 is couplable to the housing 3116 or to the
base 3158
which is coupled to the housing.
66
Date Recue/Date Received 2021-02-19
[1273] The safety guard 3130 has a first position and a second position. In
its first
position, illustrated in FIG. 78, the safety guard 3130 is coupled to the
distal end 3156 of
the housing 3116. For example, the safety guard 3130 can be coupled to a base
3128
movably coupled to the distal end 3156 of the housing 3116. In its second
position, shown
in FIG. 79, the safety guard 3130 is removed from the housing 3116. The safety
guard
3130 is removed from the housing 3116 by pulling the safety guard distally in
the
direction of arrow R.
[1274] When the safety guard 3130 is in its first position, the locking
portion 3134
inhibits or prevents actuation of the auto-injector 3006. Referring to FIG.
78, the locking
portion 3134 includes a first engagement portion 3128, or protrusion, that
extends at least
partially into the housing 3116 of the auto-injector 3006 (shown in dashed
lines). In some
embodiments, the locking portion 3134 extends through an opening (not shown in
FIG.
78) of the base 3158 movably coupled to the distal end portion 3156 of the
housing 3116,
similar to the opening 3522 defined by base 3520 as illustrated in FIG. 28.
The locking
portion 3134 is configured to keep separate the projections of the actuator,
similar to
projections 3548 of actuator 3510 illustrated in FIG. 27, when the safety
guard 3130 is in
its first position. As the safety guard 3130 is moved from its first position
to its second
position, the locking portion 3134 is removed from between the projections
3548. Thus,
the projections can be moved to actuate the auto-injector as previously
described.
[1275] When the safety guard 3130 is in its first position, the needle
guard portion
3136 substantially covers the needle (not shown) of the auto-injector 3006. As
the safety
guard 3130 is moved to its second position, the sheath retaining portion 3154
remains
coupled to the sheath 3152, and thus sheath is removed from its position
covering the
needle.
[1276] The second engagement portion 3138 of the safety guard 3130 is
configured to
be selectively coupled to at least a portion of the housing 3116 when the
safety guard 3130
is in its first position. The second engagement portion 3138, for example, can
assist in
guiding and removing the safety guard 3130 by balancing the safety guard
relative to the
housing 3116. In other words, as the safety guard 3130 is moved to its second
(or
removed) position, the second engagement portion 3138 inhibits the safety
guard 3130
from becoming skewed, and restricting movement of the first engagement portion
3128.
67
Date Recue/Date Received 2021-02-19
In some embodiments, the second engagement portion 3138 can be coupled to the
housing
3116 to prevent unwanted movement of the safety guard 3130 away from the
housing,
such as via a resistance fit with the housing.
[1277] In some embodiments, the safety guard 3130 is constructed
monolithically. In
other embodiments, the safety guard can be constructed from separate
components. For
example, one or more of the base portion, locking portion and/or needle guard
portion can
be constructed separately and then coupled to the other portions. Although the
illustrated
embodiment shows the second engagement portion 3138 as being disposed at or
proximate
to an edge of the base portion 3132, in some embodiments, the second
engagement portion
3138 can be disposed elsewhere on the base portion. Although the first
engagement
portion 3128, or locking member, is illustrated as being at or proximate to an
edge of the
base portion 3132, in some embodiments, the first engagement portion 3128 can
extend
from another portion of the base portion.
[1278] In some embodiments, a sleeve covers all or at least a substantial
portion of the
auto-injector. For example, as illustrated in FIG. 82, the sleeve 3180 covers
substantially
all of the safety guard (not shown) and the housing 3182 of the auto-injector
3007. The
sleeve 3180 can be configured for use in an embodiment having only a safety
lock or a
separate needle guard and safety lock. The sleeve 3180 has a first position in
which the
sleeve is configured to substantially cover the housing 3182, as illustrated
in FIG. 82, and
a second position in which the sleeve is configured to be removed from the
housing 3182
by pulling the sleeve distally in the direction of arrow S, as illustrated in
FIG. 83.
[1279] Although the safety lock is described as having a first engagement
portion and
a second engagement portion, in some embodiments, the safety lock has only a
first
engagement portion. For example, as illustrated in FIGS. 84 and 85, a safety
lock 3170
includes a locking portion 3174 and a needle guard portion 3176. The locking
portion
3174 has a first engagement portion 3178 disposed on the base portion 3172 of
the safety
lock. The first engagement portion 3178 extends proximally from the base
portion 3172.
The needle guard portion 3176 includes a sheath 3192 and a sheath retaining
portion 3194.
The sheath retaining portion 3194 extends proximally from the base portion
3172 and is
coupled to the sheath 31924. The sheath retaining portion 3194 is coupled to
the sheath
3192 similar to the coupling of the sheath 3820 and sheath retainer 3840 as
described in
68
Date Recue/Date Received 2021-02-19
detail above with reference to FIG. 22. The safety lock 3170 is removed by
pulling the
safety lock distally in the direction of arrow S as shown in FIG. 83, away
from housing
3182. When the safety lock 3170 is in its second (or removed) position, the
first
engagement portion 3178 is removed from between the projections of the system
actuator
rod (not shown in FIG. 83), and thus the auto-injector 3007 can be actuated.
[1280] In some embodiments, the locking member, distal end cap, safety
guard, or
sleeve are configured to mate or otherwise interface with the housing to
prevent actuation
of the auto-injector. The connection between the housing and the sleeve, for
example, can
be a snug fit and can be an interlocking connection. For example, in some
embodiments,
some force must be applied to remove the distal end cap, safety guard, or
sleeve from the
housing.
[1281] FIG. 86 is a flowchart of an embodiment of a method 20000 for
manufacturing
a medicament delivery apparatus. At 20100, a medicament container is filled
with a
predetermined amount of medicament. For example, the medicament container can
be
filled with a predetermined amount of epinephrine. As used herein, filling the
medicament
container includes putting medicament into the container, not necessarily
filling the
container to capacity. The filling of the medicament container occurs in a
sterile
environment. In some embodiments, the container can be filled with a second
medicament. In such an embodiment, the second medicament can be any
constituent of a
medicament, including water. Once the medicament container is filled, a seal
can be
placed on the container to prevent leakage and/or contamination of the
medicament. At
activity 20200, the medicament container is removed from the sterile
environment. For
example, the medicament container can be filled in a first sterile
manufacturing facility,
and then the filled containers can be transported to a second facility, which
is not
necessarily a sterile facility, to continue assembly of the apparatus.
[1282] At 20300, at least a portion of a needle is inserted into a needle
hub disposed in
or on a housing. At 20400, a needle cover, or sheath, is installed over at
least a portion of
the needle so that the needle cover substantially covers the portion of the
needle extending
from the needle hub. For example, a needle cover constructed of at least one
of
polyethylene, high density polyethylene, polypropylene,
polytetrafluoroethylene,
thermoplastic polyurethane, rubber, a polymer, or an elastomer can be
installed to cover at
69
Date Recue/Date Received 2021-02-19
least a portion of the needle extending from the needle hub. When the needle
cover is
installed, the needle cover can also be coupled to the needle hub. For
example, in some
embodiments the needle cover includes a recessed portion configured to be
coupled to a
corresponding protrusion on the needle hub. In some embodiments, the recessed
portion
and the protrusion forms a seal that is resistant to microbial penetration.
One or both of
the inserting the needle into the needle hub 20300 and installing the needle
cover 20400
can occur in a non-sterile environment.
[1283] At 20500, the needle is sterilized. Various sterilization techniques
may be
utilized. In some embodiments, a suitable sterilization technique includes the
use of one
or more of ethylene oxide, gamma radiation, e-beam radiation, ultraviolet
radiation, steam,
plasma, or hydrogen peroxide. In some embodiments, the needle is sterilized
prior to
installing the needle cover. In some embodiments, the needle is sterilized
after the needle
cover is installed. For example, in some embodiments, the needle cover is
installed and
then a gas sterilant is conveyed through at least a portion of the needle
cover. The needle
is sterilized using a gas sterilization technique that can penetrate one or
more pores of a
porous needle cover. In some embodiments, the needle can be sterilized using a
gas
sterilization technique that can penetrate one or more pores of a porous
needle cover, but
that will not react with a medicament in a medicament container disposed in
the housing.
[1284] In some embodiments, the gas sterilant is conveyed through a valve
disposed
on the needle cover. For example, the valve may be a one-way check valve, a
spring-
loaded valve, a self-sealing membrane, or the like.
[1285] At 20600, the medicament container is disposed in the housing. At
20700, a
needle guard assembly is coupled to at least one of a distal end portion of
the housing or
an actuator (or base portion) coupled to the housing. In some embodiments, the
coupling
includes coupling a one piece safety guard that is configured to prevent
actuation of the
apparatus and to receive at least a portion of the needle cover. In some
embodiments, the
coupling includes first coupling an actuation guard, or locking member,
configured to
prevent actuation of the apparatus, and then coupling a needle guard
configured to receive
at least a portion of the needle cover and to prevent movement of the locking
member
when the needle guard is coupled to the housing or the base portion.
Date Recue/Date Received 2021-02-19
[1286] Although disposing the medicament container in the housing is
illustrated and
described as occurring after the needle cover is installed over at least a
portion of the
needle, in some embodiments, the medicament container is attached to the
needle hub
when the needle cover is installed over at least a portion of the needle.
[1287] Although only the needle is illustrated and described as being
sterilized, in
some embodiments, one or more of the needle hub, needle cover, and medicament
container are sterilized in addition to the needle being sterilized. The
sterilization of the
needle hub, needle cover, medicament container and needle can occur
substantially
simultaneously or at different times.
[1288] Although the flowchart in FIG. 86 presents each activity for
manufacturing an
auto-injector in a particular order, the various activities can occur in a
different order. For
example, the medicament container can be filled with medicament after the
needle has
been sterilized. In another example, the medicament container can be disposed
in the
housing prior to inserting the portion of the needle into the needle hub.
[1289] While various embodiments of the invention have been described
above, it
should be understood that they have been presented by way of example only, and
not
limitation. Where methods described above indicate certain events occurring in
certain
order, the ordering of certain events may be modified. Additionally, certain
of the events
may be performed concurrently in a parallel process when possible, as well as
performed
sequentially as described above.
[1290] Although various embodiments have been described as having
particular
features and/or combinations of components, other embodiments are possible
having a
combination of any features and/or components from any of embodiments where
appropriate. For example, in some embodiments, an auto-injector can include a
fluidic
circuit to change the direction and/or magnitude of the force produced by the
energy
storage member and a fluid relief valve to relieve the pressure within the
fluidic circuit to
assist in the retraction of the needle. In another example, in some
embodiments, a gas
relief mechanism can include an first opening defined by the movable member
that can be
selectively placed in fluid communication with the gas chamber and an area
outside of the
gas chamber and a second opening defined by the housing that can be
selectively placed in
fluid communication with the gas chamber and an area outside of the housing.
In still
71
Date Recue/Date Received 2021-02-19
another example, in some embodiments, the sleeve 3180 illustrated in FIG. 82
can be used
in connection with the auto-injector 3002, 3004, 3006 Additionally,
any of the
components of the needle guard and safety lock can be interchanged with
similar
components in similar embodiments.
72
Date Recue/Date Received 2021-02-19
