DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Objections
Claims 60-62 are objected to because of the following informalities: the last claim set on May 19, 2025 had a previous claim 60 present. That claim appears to be missing and new claims 60-62 are presented. It is presumed that previous claim 60 is cancelled, the new claims should have correct numbering and cancelled claims should have the proper status identifier. Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 3, 4, 12, 15, 37-39, 41, 45, 46, and 50-61 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bendek et al. (US 2017/0173264 A1) in view of Bicker et al. (US 2014/0010969), Row et al. (US 2015/0165129), Bigal et al. (US 2015/0322142), Chai et al. (US 2019/0031748), Wotton et al. (US 2013/0303985 A1), Reb et al. (US 2015/001880), Cabiri et al. (US 2017/0080157), Kronestedt et al. (US 2009/0308386), and McPhee (US 5,599,315).
With regard to claims 1, 3, 4, 38, 45, and 51, Bendek et al. teach an auto injector apparatus comprising: a syringe (Fig. 2 member 20) comprising: a barrel comprising an inner surface (Fig. 2 barrel of 20); a needle at a distal end of the barrel, the needle having an inner diameter less than an inner diameter of the barrel (Fig. 5 needle 134); a therapeutic fluid ([0010] medicament) held within the barrel; and a stopper disposed within the barrel, the stopper being configured to move axially within the barrel between an initial position and a final position to expel a full dose of the therapeutic fluid from the syringe (Fig. 3 member 21); and an auto injector that holds the syringe (Fig. 2 at least member 10), the auto injector comprising: a rod (Fig. 6 member 76) configured to move the stopper; and an injection spring configured drive the rod to move the stopper from the initial position to the final position, (Fig. 6 member 82, [0051]).
Bendek et al. do not disclose lubrication on the inner surface of the barrel.
In related prefilled syringe prior art, Bicker teaches silicone-based oil lubricating layers for syringe barrel interiors is well known in various industry prior arts (Bicker [0003]).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe barrel of Bendek et al. to include silicone-based oil lubricating layers on the syringe barrel interior, as taught by Bicker, for the motivation of having beneficial breakaway (break-loose) force or static friction reduction (Bicker [0007]).
Bendek et al. teach various volumes may be delivered and the movement of the stopper is taken to correspond to one dose ([0010], [0016]) but do not specifically reach a 1mL dose. Bendek et al. do not recite the specific length or diameter of the needle. However, Row et al. teach the volume of a syringe reservoir may vary and may include 1mL ([0077]). Row et al. teach the syringe (Row (104)) having a needle (Row Fig. 2A, (406)) on a distal end of the syringe barrel, further teaching the needle can be any of a range of gauges including 7 gauge through 33 gauge, having needle lengths of 3mm through 40mm or more; the needle is sized to provide flow as appropriate for the intended use (Row [0085]). As a 25-gauge needle is taught among the possible needles claimed by Row et al., and as it is well known in the art that a 25-gauge needle has an inner diameter that is about 0.25mm to 0.29mm, Row et al. also teaches having a needle inner diameter of about 0.27mm. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the volume and needle inner diameter/length of Bendek et al. as recited as Row et al. teach the volume recited and that needle length and gauge may be selected as appropriate for the intended use and since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. MPEP 2144.05(II)(A). Further, it is well known that the dose is based on various treatment factors including the substance being delivered and particular patient parameters.
Benedek et al. teach delivering a medicament (abstract) but do not disclose the specific substance and viscosity delivered. In related prior art, Bigal et al. teach a therapeutic for injection to adult patients, wherein the therapeutic being injected is an anti-calcitonin gene-related peptide antibody (Bigal [0029] wherein anti-CGRP is an antagonist antibody, known as antibody G1). Bigal et al. teach the volume may vary based on various conditions and may include a volume of 1mL. Bigal et al. teach the viscosity may vary depending on desired efficacy, safety, and storage considerations ([0155]). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to modify the therapeutic delivered by the device of Bendek et al., to be anti-CGRP, as taught by Bigal et al., for the motivation of delivering subcutaneous preventative treatments for common ailments such as migraines (Bigal [0033]) and additionally to use a volume and viscosity as recited as it is a known treatment volume depending on desired conditions and viscosity may be selected depending on desired efficacy, safety, and storage considerations.
Bendek et al. doesn’t explicitly teach wherein the anti-CGRP antibody comprises a heavy chain variable region that is at least 90%, 95%, or 100% identical in amino acid sequence to SEQ ID NO: 1 and a light chain variable region that is at least 90%, 95%, or 100% identical in amino acid sequence to SEQ ID NO: 2.
In related therapeutic delivery prior art, Chai teaches various antibodies that bind calcitonin gene-related peptide (CGRP), wherein the anti-CGRP antibody comprises a heavy chain variable region that is at least 90%, 95%, or 100% identical in amino acid sequence to SEQID NO: 1 and a light chain variable region that is at least 90%, 95%, or 100% identical in amino acid sequence to SEQ ID NO: 2 ({0005] wherein a combination of heavy chain variable regions and light chain variable regions of SEQ ID NO: 1 and SEQ ID NO: 2 is taught in the prior art).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the anti-CGRP antibody of Bendek et al. to be a heavy chain variable region at least 90%, 95%, or 100% identical to SEQID NO: 1 and a light chain variable region at least 90%, 95%, or 100% identical to SEQ ID NO: 2; all as taught by Chai, as these and various other combinations are known in the prior art for treating migraines, cluster headaches, and osteoarthritis pain (Chai [0002]).
Bendek et al. do not teach a particular shelf life or that the stored energy is 25% greater than energy sufficient to move the stoper when the syringe is unaged. However, Row et al. teach a syringe may have modifications to the syringe body and seal and that the shelf life of a therapeutic may vary between 1 to 5 years ([0084]). Additionally, Wotton et al. teach constructing a syringe spring out of a material that is resilient so as to no lose force over time during the shelf life of the syringe ([0080]). Further, Reb et al. teach artificially aging syringes using heat to simulate one to three years of natural aging and that when syringes sit with a substance it can interfere with the loading ([0024], [0025], [0048], [0049]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have a shelf life of the fluid in Bendek et al. to be 24 months as Row et al. teach such is a suitable storage time for a therapeutic agent and to test the conditions in an artificially aged syringe of Bendek et al. as in Reb et al. as this allows the necessary factors to be determined for actual shelf life and to select a suitable spring material as in Wotton et al. such that the spring is able to eject a fluid during the shelf life of the syringe. and to select a suitable spring material as in Wotton et al. such that the spring is able to eject a fluid during the shelf life of the syringe. Further, one of ordinary skill would recognize the shelf life would vary depending on known factors such as the agent itself and storage conditions and it would further be obvious since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. MPEP 2144.05(II)(A). As it is known that an aged syringe must overcome conditions related to sitting one of ordinary skill would be able to design a spring to achieve desired force conditions in an aged syringe which would differ form an unaged syringe.
Bendek et al. do not teach a spring configured to move the stopper within a period of 5 to 25 seconds, an initial force of between 20 N and 30 N, and a final dispensing force of between 12 N to about 20 N.
However, Cabiri et al. teach an auto injector apparatus (seen in Fig. 4A) comprising a stopper (Fig. 4A, (426)) and a spring ([0186] wherein the power supply (for delivering a single dose payload) can be mechanical means such as a spring). Cabiri et al. [0188] teaches a range of force may be applied to the stopper (plunger) during injection, anywhere between 5N - 60N, depending upon factors such as injection rate and/or the viscosity of the drug and/or the syringe geometry and/or the needle dimensions. Cabiri et al. teach the payload may be delivered over a time period of 20-120 seconds ([0186]) and that timing depends on fill volume and viscosity ([0192]).
Further, related prior art Kronestedt et al. ([0004-0005]) teaches when a force is applied to a piston during medicament delivery by a pre-tensioned spring associated with the plunger rod, that force is obtained in accordance with Hooke's law. Hooke’s law states force exerted by a spring is a function of displacement of the spring from its original position, multiplied by the spring constant. Therefore, from Hooke’s law it follows that force acting on the piston will decline linearly as the piston moves forward during injection, due to a decompressing spring naturally having reduced dispensing force. Additionally, McPhee teaches that as a spring decompresses the force decreases by about 20% to the final dispensing position (Col. 3 line 21-26).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have timing and force values as recited in Bendek et al. as Cabiri et al. teach the spring may be selected to deliver a force as desired based on variables including injection rate, viscosity, syringe geometry, and needle dimensions. Further, delivery time would also be a result of factors tied to the spring selection including viscosity and fill volume. As the initial force value would be selected as taught by Cabiri et al. it would follow that the final dispensing force would be at least 50% of the initial value as Kronestedt et al. teach from Hooke’s law it follows that the force decreases as the piston moves during injection and McPhee discloses that the force decreases by about 20%, thus it would be about 80% of the initial force.
It has been held that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.” In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575,16 USPQ2d 1934 (Fed. Cir. 1990). As Cabiri et al. teach that the spring may be selected for the desired conditions and performance and Kronestedt et al. and McPhee teach spring behavior as recited one of ordinary skill in the art would have had a reasonable expectation of success in modifying Bendek et al. to have the necessary spring characteristics to achieve the desired force and timing. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use such a range for timing and force as claimed in Bendek et al. as Cabiri et al. teach such to be result effective variables that may be selected for the desired conditions and performance and Kronestedt et al. and McPhee teach known spring behavior selecting the spring to have the timing and force fall within the claimed range would have been a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105, USPQ 233, 235 (CCPA 1955).
With regard to claim 12, Bendek et al. teach a device substantially as claimed and the injection spring would necessarily have a stored spring constant. The combination doesn’t explicitly teach before the auto injector is actuated, the stored spring constant between about 0.2 N/mm and about 0.4 N/mm and has a compressed length of between about 50 mm and about 100 mm.
However, the provided disclosure sets forth that “a spring constant in the range from about 0.2 N/mm to about 0.4 N/mm” and “a compressed length in the range from about 50 mm to about 100 mm” is a result effective variable, wherein the provided disclosure merely describes the range of spring constants and compressed lengths are a preferable range and are variable depending on varying embodiments.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the spring constant and spring compressed length of the spring of Bendek et al. for the purpose of providing a desired force as Kronestedt et al. ([0004-0005]) teach that according to Hooke’s Law, the spring constant and spring compression length are factors effecting the force provided by any spring; and since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. MPEP 2144.05(11)(A), In re Aller, 220 F.2d 454, 456, 105, USPQ 233, 235 (CCPA 1955).
With regard to claim 15, Bendek et al. teach the syringe may be made of glass ([0033]) and as combined with Bicker the lubricant is a silicone oil.
With regard to claim 37, Bendek et al. teach the modified auto injector apparatus of claim 1. Bendek et al. teach a stopper having a main body that is substantially cylindrical (seen in Fig. 1, wherein (19) is substantially cylindrical).
The combination doesn’t explicitly teach wherein: the stopper is configured to compress to a compressed state and relax to an uncompressed state, and the stopper comprises: a main body that has a diameter in the uncompressed state of between about 8.85 mm and about 9.05 mm; and an annular rib extending radially from the main body, the annular rib having an outer diameter in the uncompressed state of between about 9.25 mm and about 9.45 mm.
In related prior art, Wotton teaches an auto injector (Fig. 2) having a syringe (Fig. 2, (18) including (20)) and a stopper (Fig. 2, (28)) wherein the stopper has a compressed state (seen in Fig. 6D, wherein the stopper is compressed at the end of delivery by the (ram) piston rod (60)) and an uncompressed state (seen in Fig. 6A, wherein the stopper is uncompressed in the pre - delivery state), and the stopper comprises: a main body (Fig. 6A, (28)), the main body being substantially cylindrical (seen in Fig. 2 and Fig. 6A, wherein the stopper (28) has a substantially cylindrical body).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the stopper of Bendek et al. to have a compressed and uncompressed state, as taught by Wotton, since it is well known in the art that stoppers are often made of flexible material.
The combination doesn’t teach the stopper comprises: a diameter in the uncompressed state of between about 8.85 mm and about 9.05 mm; and an annular rib extending radially from the main body, the annular rib having an outer diameter in the uncompressed state of between about 9.25 mm and about 9.45 mm.
In related prior art, Row teaches an auto injector (Fig. 1, (100)) having a stopper (Fig. 2E, (410)) wherein the stopper has at least one annular rib (Row Fig. 2E, wherein the stopper main boy is (410)), the annular rib extending radially from the main body (Row Fig. 2E, annular ribbing is show extending radially from the main body of stopper (410)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the stopper of Bendek et al. to have an annular rib extending radially from the main body, as taught by Row, for the motivation of creating an effective seal with the inner surface of the syringe body reservoir to limit the contents of the syringe cavity from flowing or otherwise moving proximally (Row [0077]).
While Bendek et al. do not explicitly teach the stopper having a diameter in the uncompressed state in the range from about 8.85 mm to about 9.05 mm; the annular rib having an outer diameter in the uncompressed state in the range from about 9.25 mm to about 9.45 mm, the provided disclosure sets forth that “a stopper uncompressed diameter in the range from about 8.85 mm to about 9.05 mm” and “a stopper annular rib outer diameter in the range from about 9.25 mm to about 9.45 mm” area result effective variable, wherein the provided disclosure merely describes the range of stopper diameters which may be any value within the provided ranges.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the stopper and annular rib outer diameters in uncompressed states, of Bendek et al. for the purpose of providing greater or lesser force to therapeutics contained within the prefilled syringes depending upon their viscosities, which decreases overall injection time to increase patient compliance, and thus, the patient will experience less pain (Wotton [0078]); also since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. MPEP 2144.05(II)(A).
With regard to claims 39 and 41, Bendek et al. ([0016]) teach the linear distance the plunger rod (and hence stopper) moves during expelling of medicament is a distance which corresponds to dose volume; it is advantageous that the dose volume can be determined and also altered by choosing the linear distance the plunger rod (and hence the stopper) can travel when acting on a medicament container with a certain total volume.
The claimed limitations set forth that the “the distance between the first position and the second position is between about 25.7 mm and about 30 mm”. Regarding the provided specification, (SPEC [0057]) sets forth “The path of travel, P, can be about 29.6 mm, which is sometimes referred to as a "30mm" path of travel. In alternative embodiments, the path of travel, P, can be in the range from about 25.7 mm to about 28.2 mm, from about 25 mm to about 29 mm, or from about 25 mm to about 40 mm. In some embodiments, the path of travel, P, can be 29.6 mm. In other embodiments, the length of the path of travel, P, can be a distance outside these ranges” as originally filed. Therefore, there is a lack of criticality in the dimensions set forth by the claim. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the distance between the first and second positions of the stopper of Bendek et al. to be between about 25.7 mm and about 30 mm or about 35 mm to about 55 mm, since Bendek et al. ([0016]) teach the linear distance the plunger rod and stopper moves during expelling of medicament is a distance which corresponds to dose volume, and thus can be predetermined to have a set volume delivered per dose; and since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. MPEP 2144.05(II)(A).
With regard to claims 53-56, see exemplary Fig. 8 showing the arrangement of the spring and rod.
With regard to claims 46, 50, 52, 60, and 61, Bendek et al. teach an auto injector apparatus comprising: a syringe (Fig. 2 member 20) comprising: a barrel (Fig. 2 barrel of 20); a needle at a distal end of the barrel, the needle having an inner diameter less than an inner diameter of the barrel (Fig. 5 needle 134) a therapeutic fluid ([0010] medicament) held within the barrel; and a stopper disposed within the barrel, the stopper being configured to move axially within the barrel between an initial position and a final position to expel a full dose of the therapeutic fluid from the syringe (Fig. 3 member 21); and an auto injector that holds the syringe (Fig. 2 at least member 10), the auto injector comprising: a rod (Fig. 6 member 76) configured to move the stopper; and an injection spring configured drive the rod to move the stopper from the initial position to the final position, (Fig. 6 member 82, [0051]).
Bendek et al. do not disclose lubrication on the inner surface of the barrel.
In related prefilled syringe prior art, Bicker teaches silicone-based oil lubricating layers for syringe barrel interiors is well known in various industry prior arts (Bicker [0003]).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe barrel of Bendek et al. to include silicone-based oil lubricating layers on the syringe barrel interior, as taught by Bicker, for the motivation of having beneficial breakaway (break-loose) force or static friction reduction (Bicker [0007]).
Bendek et al. doesn’t explicitly teach wherein the anti-CGRP antibody comprises a heavy chain variable region that is at least 90%, 95%, or 100% identical in amino acid sequence to SEQ ID NO: 1 and a light chain variable region that is at least 90%, 95%, or 100% identical in amino acid sequence to SEQ ID NO: 2.
In related therapeutic delivery prior art, Chai teaches various antibodies that bind calcitonin gene-related peptide (CGRP), wherein the anti-CGRP antibody comprises a heavy chain variable region that is at least 90%, 95%, or 100% identical in amino acid sequence to SEQID NO: 1 and a light chain variable region that is at least 90%, 95%, or 100% identical in amino acid sequence to SEQ ID NO: 2 ({0005] wherein a combination of heavy chain variable regions and light chain variable regions of SEQ ID NO: 1 and SEQ ID NO: 2 is taught in the prior art).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the anti-CGRP antibody of Bendek et al. to be a heavy chain variable region at least 90%, 95%, or 100% identical to SEQID NO: 1 and a light chain variable region at least 90%, 95%, or 100% identical to SEQ ID NO: 2; all as taught by Chai, as these and various other combinations are known in the prior art for treating migraines, cluster headaches, and osteoarthritis pain (Chai [0002]).
Bendek et al. teach various volumes may be delivered and the movement of the stopper is taken to correspond to one dose ([0010], [0016]) but do not specifically reach a 1mL dose. Bendek et al. do not recite the specific length or diameter of the needle. However, Row et al. teach the volume of a syringe reservoir may vary and may include 1mL ([0077]). Row et al. teach the syringe (Row (104)) having a needle (Row Fig. 2A, (406)) on a distal end of the syringe barrel, further teaching the needle can be any of a range of gauges including 7 gauge through 33 gauge, having needle lengths of 3mm through 40mm or more; the needle is sized to provide flow as appropriate for the intended use (Row [0085]). As a 25-gauge needle is taught among the possible needles claimed by Row et al., and as it is well known in the art that a 25-gauge needle has an inner diameter that is about 0.25mm to 0.29mm, Row et al. also teaches having a needle inner diameter of about 0.27mm. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the volume and needle inner diameter/length of Bendek et al. as recited as Row et al. teach the volume recited and that needle length and gauge may be selected as appropriate for the intended use and since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. MPEP 2144.05(II)(A). Further, it is well known that the dose is based on various treatment factors including the substance being delivered and particular patient parameters.
Benedek et al. teach delivering a medicament (abstract) but do not disclose the specific substance and viscosity delivered. In related prior art, Bigal et al. teach a therapeutic for injection to adult patients, wherein the therapeutic being injected is an anti-calcitonin gene-related peptide antibody (Bigal [0029] wherein anti-CGRP is an antagonist antibody, known as antibody G1). Bigal et al. teach the volume may vary based on various conditions and may include a volume of 1mL. Bigal et al. teach the viscosity may vary depending on desired efficacy, safety, and storage considerations ([0155]). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to modify the therapeutic delivered by the device of Bendek et al., to be anti-CGRP, as taught by Bigal et al., for the motivation of delivering subcutaneous preventative treatments for common ailments such as migraines (Bigal [0033]) and additionally to use a volume and viscosity as recited as it is a known treatment volume depending on desired conditions and viscosity may be selected depending on desired efficacy, safety, and storage considerations.
Bendek et al. do not teach a particular shelf life. However, Row et al. teach a syringe may have modifications to the syringe body and seal and that the shelf life of a therapeutic may vary between 1 to 5 years ([0084]). Additionally, Wotton et al. teach constructing a syringe spring out of a material that is resilient so as to no lose force over time during the shelf life of the syringe ([0080]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have a shelf life of the fluid in Bendek et al. to be 24 months as Row et al. teach such is a suitable storage time for a therapeutic agent and to select a suitable spring material as in Wotton et al. such that the spring is able to eject a fluid during the shelf life of the syringe. Further, one of ordinary skill would recognize the shelf life would vary depending on known factors such as the agent itself and storage conditions and it would further be obvious since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. MPEP 2144.05(II)(A).
Bendek et al. do not teach a particular shelf life or that the stored energy is 25% greater than energy sufficient to move the stoper when the syringe is unaged. However, Row et al. teach a syringe may have modifications to the syringe body and seal and that the shelf life of a therapeutic may vary between 1 to 5 years ([0084]). Additionally, Wotton et al. teach constructing a syringe spring out of a material that is resilient so as to no lose force over time during the shelf life of the syringe ([0080]). Further, Reb et al. teach artificially aging syringes using heat to simulate one to three years of natural aging and that when syringes sit with a substance it can interfere with the loading ([0024], [0025], [0048], [0049]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have a shelf life of the fluid in Bendek et al. to be 24 months as Row et al. teach such is a suitable storage time for a therapeutic agent and to test the conditions in an artificially aged syringe of Bendek et al. as in Reb et al. as this allows the necessary factors to be determined for actual shelf life and to select a suitable spring material as in Wotton et al. such that the spring is able to eject a fluid during the shelf life of the syringe. and to select a suitable spring material as in Wotton et al. such that the spring is able to eject a fluid during the shelf life of the syringe. Further, one of ordinary skill would recognize the shelf life would vary depending on known factors such as the agent itself and storage conditions and it would further be obvious since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. MPEP 2144.05(II)(A). As it is known that an aged syringe must overcome conditions related to sitting one of ordinary skill would be able to design a spring to achieve desired force conditions in an aged syringe which would differ form an unaged syringe.
Bendek et al. do not teach a spring configured to move the stopper within a period of 5 to 25 seconds, an initial force of between 20 N and 30 N, and a final dispensing force of between 12 N to about 20 N.
However, Cabiri et al. teach an auto injector apparatus (seen in Fig. 4A) comprising a stopper (Fig. 4A, (426)) and a spring ([0186] wherein the power supply (for delivering a single dose payload) can be mechanical means such as a spring). Cabiri et al. [0188] teaches a range of force may be applied to the stopper (plunger) during injection, anywhere between 5N - 60N, depending upon factors such as injection rate and/or the viscosity of the drug and/or the syringe geometry and/or the needle dimensions. Cabiri et al. teach the payload may be delivered over a time period of 20-120 seconds ([0186]) and that timing depends on fill volume and viscosity ([0192]).
Further, related prior art Kronestedt et al. ([0004-0005]) teaches when a force is applied to a piston during medicament delivery by a pre-tensioned spring associated with the plunger rod, that force is obtained in accordance with Hooke's law. Hooke’s law states force exerted by a spring is a function of displacement of the spring from its original position, multiplied by the spring constant. Therefore, from Hooke’s law it follows that force acting on the piston will decline linearly as the piston moves forward during injection, due to a decompressing spring naturally having reduced dispensing force. Additionally, McPhee teaches that as a spring decompresses the force decreases by about 20% to the final dispensing position (Col. 3 line 21-26).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have timing and force values as recited in Bendek et al. as Cabiri et al. teach the spring may be selected to deliver a force as desired based on variables including injection rate, viscosity, syringe geometry, and needle dimensions. Further, delivery time would also be a result of factors tied to the spring selection including viscosity and fill volume. As the initial force value would be selected as taught by Cabiri et al. it would follow that the final dispensing force would be at least 50% of the initial value as Kronestedt et al. teach from Hooke’s law it follows that the force decreases as the piston moves during injection and McPhee discloses that the force decreases by about 20%, thus it would be about 80% of the initial force.
It has been held that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.” In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575,16 USPQ2d 1934 (Fed. Cir. 1990). As Cabiri et al. teach that the spring may be selected for the desired conditions and performance and Kronestedt et al. and McPhee teach spring behavior as recited one of ordinary skill in the art would have had a reasonable expectation of success in modifying Bendek et al. to have the necessary spring characteristics to achieve the desired force and timing. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use such a range for timing and force as claimed in Bendek et al. as Cabiri et al. teach such to be result effective variables that may be selected for the desired conditions and performance and Kronestedt et al. and McPhee teach known spring behavior selecting the spring to have the timing and force fall within the claimed range would have been a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105, USPQ 233, 235 (CCPA 1955).
With regard to claims 57-59, see exemplary Fig. 8 showing the arrangement of the spring and rod.
Claims 6 and 62 are rejected under 35 U.S.C. 103 as being unpatentable over Bendek et al. (US 2017/0173264 A1), Bicker et al. (US 2014/0010969), Row et al. (US 2015/0165129), Bigal et al. (US 2015/0322142), Chai et al. (US 2019/0031748), Wotton et al. (US 2013/0303985 A1), Reb et al. (US 2015/001880), Cabiri et al. (US 2017/0080157), Kronestedt et al. (US 2009/0308386), and McPhee (US 5,599,315) as applied to Claims 1 and 46 above, further in view of Lazar et al., (US 2017/0252437).
With regard to claims 6 and 62, Bendek et al. teach the modified auto injector apparatus of claim 1, wherein the therapeutic fluid (Bendek (31)) comprises a liquid pharmaceutical combination (Bendek [0066] wherein the antibody or peptide or protein, or a mixture of the above-mentioned pharmaceutically active compounds are liquid pharmaceutical combinations).
The prior art combination doesn’t explicitly teach the liquid pharmaceutical composition comprising: about 225 mg of the anti-CGRP antibody, about 0.204 mg disodium ethylenediaminetetraacetic acid dihydrate (EDTA); about 0.815 mg L- histidine; about 3.93 mg L-histidine hydrochloride monohydrate; about 0.3 mg polysorbate -80; about 99 mg sucrose; and water, wherein liquid pharmaceutical composition for injection has a pH of 5.5.
Bendek et al. do not explicitly teach the liquid pharmaceutical composition comprising about 0.204 mg disodium ethylenediaminetetraacetic acid dihydrate (EDTA); about 0.815 mg L-histidine; about 3.93 mg L- histidine hydrochloride monohydrate; about 0.3 mg polysorbate -80; about 99 mg sucrose; and water, wherein liquid pharmaceutical composition for injection has a pH of 5.5.
In related prior art, Lazar teaches various formulations of anti-CGRP antibody, formulated at 225 mg (Lazar [0040]) including histidine (Lazar [0025]), sucrose (Lazar [0116]), disodium ethylenediaminetetraacetic acid dihydrate (EDTA) (Lazar [0025] and [0128]) and polysorbate-80, all of which have a pH in range of 5 - 5.5 (Lazar [0025]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the anti-CGRP antibody of Bendek et al. to be formulated at 225 mg having a pH 5.5; all as taught by Lazar, as these and various other combinations are already established in the prior art for treating known conditions such as migraines, cluster headaches, and osteoarthritis pain (Chai [0002]).
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Bendek et al. (US 2017/0173264 A1), Bicker et al. (US 2014/0010969), Row et al. (US 2015/0165129), Bigal et al. (US 2015/0322142), Chai et al. (US 2019/0031748), Wotton et al. (US 2013/0303985 A1), Reb et al. (US 2015/001880), Cabiri et al. (US 2017/0080157), Kronestedt et al. (US 2009/0308386), and McPhee (US 5,599,315), as applied to Claim 1 above, further in view of Atterbury et al. (US 2018/0200442).
With regard to claim 16, Bendek et al. teach the modified auto injector apparatus of claim 1. The combination is silent to wherein the stopper is coated with a first coating comprising ethylene tetrafluoroethylene, and a second coating comprising silicone, and the first coating coats a first portion of the stopper and the second coating coats a second portion of the stopper that is different from the first portion of the stopper.
In related prior art, Atterbury teaches an auto injector apparatus (Figs 1 and 5) with a stopper (Fig. 5, (72)) and spring (Fig. 1, (22)) wherein a first portion of the stopper is coated with silicone ([0067] wherein portions of the injector are lubricated with a lubricant, such as silicone oil, between surfaces that slide over each other during operation. Hence the stopper).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the stopper of Bendek et al. have a coating of silicone on at least a first portion, as taught by Atterbury, for the motivation of lubricant such as silicone oil allowing surfaces to slide over each other during operation (Atterbury [0067]), hence allowing easier movement of the stopper.
The combination still doesn’t explicitly teach another second portion of the stopper is coated in ethylene tetrafluoroethylene.
In related prefilled syringe prior art, Bicker teaches silicone-based oil lubricating layers for syringe barrel interiors is well known in various industry prior arts (Bicker [0003]), and teaches coating a stopper with ethylene tetrafluoroethylene (Bicker [0071] wherein silicone - free ethylene combinations are also used as lubricant).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the stopper of Bendek et al., such that the lubricants on other (second) portions of stoppers could be ethylene tetrafluoroethylene, as taught by Bicker, for the motivation of reducing the amount of static friction or breakaway force between the inner surface of the syringe barrel and the stopper (Bicker [0007]).
Claims 31 and 43 is rejected under 35 U.S.C. 103 as being unpatentable over Bendek et al. (US 2017/0173264 A1), Bicker et al. (US 2014/0010969), Row et al. (US 2015/0165129), Bigal et al. (US 2015/0322142), Chai et al. (US 2019/0031748), Wotton et al. (US 2013/0303985 A1), Reb et al. (US 2015/001880), Cabiri et al. (US 2017/0080157), Kronestedt et al. (US 2009/0308386), and McPhee (US 5,599,315), as applied to Claim 1 above, further in view of Berg et al. (US 2018/0243508).
With regard to claims 31 and 43, Bendek et al. teach the syringe may be made of glass ([0033]) and as combined with Bicker the lubricant is a silicone oil. Bendek et al. do not teach the barrel diameter. In related prior art, Berg teaches an injection device (Berg Fig. 1, (10)) including a syringe (Berg Fig. 1, (10)) having a needle (Berg Fig. 1, (30)) at the distal end of the barrel (Berg Fig. 1, (20)), and a stopper (Berg Fig. 1, (40)) within the barrel of the syringe. Berg teaches the syringe having a sealing surface with a diameter between about 5mm and about 14mm (Berg [0052]); thus, if Berg has a stopper with a diameter of about 8mm or about 9mm, the syringe barrel inner diameter would have to accordingly be about 8.65mm, to creating the sliding seal (sealing surface) of the stopper (Berg (40)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe barrel inner diameter of Bendek et al. to be about 8.65 mm, as taught by Berg, for the motivation of having an ideal compressibility ratio between the outer diameter of the stopper and the inner surface of the syringe barrel (Berg [0054]) when delivering therapeutic contained within the syringe barrel.
Response to Arguments
Applicant’s arguments with respect to the claim(s) have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Applicant argues that if the factors of Cabiri et al. are considered, and values such as those claimed were selected, one of ordinary skill would select force values other than those claimed. Applicant argues that artificial aging exaggerates changes that increase resistive forces acting on the stopper as compared to natural aging. As currently rejected Cabiri et al. is considered in conjunction with at least Row et al., Wotton et al., and Reb et al. Reb et al. shows it is known to test syringes which have been artificially aged to determine syringe function, Row et al. and Wotton et al. further speak to the shelf-life of syringes and maintaining syringe performance over the shelf-life of the syringe. Though Wotton does not explicitly disclose having stored energy 25% greater than a minimum amount of an unaged syringe, when considered with the references together one of ordinary skill would determine the spring need to perform as desired after aging. Given these teachings the Examiner finds one of ordinary skill would be able to determine the spring characteristics needed for injection based on the conditions of an unaged or aged syringe. Applicant argues one would not look to Cabiri’s spring as it is different from Bendek’s spring. Both springs are used to drive syringe plunger to deliver medication. One of ordinary skill would look to how to optimize spring performance over various syringe systems which use spring drives.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/EMILY L SCHMIDT/Primary Examiner, Art Unit 3783