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 Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-28 are rejected under 35 U.S.C. 103 as being unpatentable over Weikart et al. (US 2015/0335823 A1) in view of Groner et al. (Applied Physics Letters 88, 051907 (2006): Gas diffusion barriers on polymers using Al2O3 atomic layer deposition) and in further view of Dameron et al. (J. Phys. Chem. C 2008, 112, 4573-4580: Gas Diffusion Barriers on Polymers Using Multilayers Fabricated by Al2O3 and Rapid SiO2 Atomic Layer Deposition).
Regarding claim 1, Weikart discloses a drug primary package (Fig. 8, feat. 10; ¶0118-0119 and 0193-0198) comprising: a thermoplastic vial (10; ¶0160, 0193-0198, and 0240) comprising a lumen defined at least in part by a side wall and a bottom wall (18; ¶0240), the side wall having an interior surface facing the lumen and an outer surface (Fig. 8; ¶0240-0241), the bottom wall having an upper surface facing the lumen and a lower surface (Fig. 8; ¶0240-0241); an opening to the lumen located opposite the bottom wall (Fig. 8); and a gas barrier coating (Fig. 8, feat. 30; ¶0240-0249) supported by at least one of the interior surface (Fig. 8, feat. 16; ¶0240-0241) and the outer surface of the wall; a stopper seated in the opening (Fig. 8, feat. 270; ¶0110 and Table 1); and a lyophilized drug formulation in the lumen (¶0009 and 0015).
Weikart does not disclose that the gas barrier coating is effective to provide the package with an oxygen transmission rate constant less than 0.0010 d-1; and to reduce the ingress of water vapor into the lumen to less than 0.25 mg/package/day when stored at 40.0 °C and 75% relative humidity; and wherein the vial has a heat transfer coefficient (Kv x104) of at least 3.3 cals/cm2/°C.
Groner teaches that atomic layer deposition (ALD) deposits smooth, conformal, and pinhole-free films which are suitable for creating the defect-free films needed for superior gas diffusion barriers (Page 051907-1, col. 1, line 1 – col. 2, line 10). As discussed in ¶0446 of the present specification, coatings applied by ALD consist of a plurality of monolayers of the deposited compound. Groner further teaches that ALD deposited Al2O3 films with thicknesses between 5 nm and 26 nm achieve oxygen transmission rates (OTR) less than 0.005 cc/m2/day, which are superior in performance to the OTR achieved by much thicker, >100 nm films of PECVD SiO2 (Page 051907-2, col. 1, lines 2-25). Groner further teaches that ALD deposited Al2O3 films with thicknesses between 5 nm and 26 nm achieve water vapor transmission rates (WVTR) between about 100 mg/m2/day and about 1 mg/m2/day, which are superior in performance to the WVTR achieved by much thicker, >100 nm films of PECVD SiO2 (Page 051907-2, col 2, lines 10-42). Therefore, Groner suggests that ALD Al2O3 coatings have better oxygen and water vapor barrier properties than PECVD SiO2 coatings due to the smooth, conformal, and pinhole-free films created by ALD.
Dameron teaches that single layer ALD Al2O3 gas diffusion barriers are subject to corrosion by water which may lead to barrier failure (Page 4576, col 1, line 60 – col. 2, line 21). Dameron further teaches that an ALD Al2O3 may be protected from this corrosion by the deposition of an ALD SiO2 layer, forming alternating multilayer films of 26 nm Al2O3 and 60 nm SiO2, which also improves the gas barrier properties compared to the bare ALD Al2O3 films (Page 4573, Abstract; Page 4576, col. 2, line 22 – Page 4577, col. 2, line 15; Page 4578, section B). Therefore, Dameron suggests that bilayers comprising 26 nm Al2O3 and 60 nm SiO2 deposited by ALD have better barrier properties than ALD Al2O3 films on their own.
Weikart discloses that the barrier coating or layer may be a PECVD SiO2 layer with a thickness between 2 nm and 1000 nm (¶0243-0249). As discussed above, Groner suggests that ALD Al2O3 coatings have better oxygen and water vapor barrier properties than PECVD SiO2 and Dameron suggests that a bilayer comprising 26 nm Al2O3 and 60 nm SiO2 deposited by ALD have better barrier properties than ALD Al2O3 films on their own. Therefore, modifying the package of Weikart so that the barrier coating or layer comprising a bilayer comprising 26 nm Al2O3 and 60 nm SiO2 deposited by ALD would improve the gas barrier properties of the package as taught by Groner and Dameron. Groner reports OTRs measured at 23 °C and 50% relative humidity, and therefore Weikart in view of Groner and in further view of Dameron do not explicitly disclose the claimed oxygen transmission rate constant less than 0.0010 d-1. Groner and Dameron report WVTRs measured at unknown temperatures and 100% relative humidity, and therefore Weikart in view of Groner and in further view of Dameron do not explicitly disclose the claimed water vapor ingress rate of less than 0.25 mg/package/day when stored at 40.0 °C and 75% relative humidity. Weikart in view of Groner and in further view of Dameron do not disclose the claimed heat transfer coefficient. However the barrier in the package of Weikart in view of Groner and in further view of Dameron comprises 26 nm of Al2O3 deposited by ALD and 60 nm of SiO2 deposited by ALD, resulting in an 86 nm thick barrier, and Weikart discloses a vial with a substantially flat bottom (Fig. 8) made of cyclic olefin polymer (COP) (¶0160 and 0193), and therefore the vial of Weikart in view of Groner and in further view of Dameron comprises a COP vial with a gas barrier deposited by ALD. The gas barrier of the present application may similarly comprise a water vapor barrier layer comprising Al2O3 deposited by ALD and an oxygen barrier comprising SiO2 deposited by ALD, with a total thickness between 2 nm and 1000 nm, and achieve an oxygen transmission rate constant less than 0.0010 d-1 and a water vapor ingress rate of less than 0.25 mg/package/day when stored at 40.0 °C and 75% relative humidity (Present specification: ¶0013-0016, 0471, 0479-0480, 0523-0525). Furthermore, the vial of the present application achieves a heat transfer coefficient (Kv x104) of at least 3.3 cals/cm2/°C by being made of COP, having the ALD deposited gas barrier, and by having a flat bottom (Present specification: ¶0531-0534 and Table A1). Therefore, the vial and gas barrier suggested by Weikart in view of Groner and in further view of Dameron is structurally and compositionally identical to the vial and gas barrier of the present application, and would therefore be expected to have the same properties. Please see MPEP §2112.01(II). Therefore, Weikart in view of Groner and in further view of Dameron inherently discloses that the gas barrier coating is effective to provide the package with an oxygen transmission rate constant less than 0.0010 d-1; and to reduce the ingress of water vapor into the lumen to less than 0.25 mg/package/day when stored at 40.0 °C and 75% relative humidity; and wherein the vial has a heat transfer coefficient (Kv x104) of at least 3.3 cals/cm2/°C. Please see MPEP §2112.
Regarding claims 2 and 4, Weikart in view of Groner and in further view of Dameron suggests the package of claim 1. As discussed above, the package and gas barrier suggested by Weikart in view of Groner and in further view of Dameron is structurally and compositionally identical to the claimed package and gas barrier, and would therefore be expected to have the same properties. Please see MPEP §2112.01(II). With respect to claim 2, the present specification indicates that a plurality of such vials would have a standard deviation of the heat transfer coefficient across a plurality of vials less than 0.15 cals/cm2/°C (Present specification: ¶0531-0534 and Table A1). With respect to claim 4, the present specification indicates that such a vial with a flat bottom would produce an ink blot that covers at least 60^% of the footprint of the vial (Present specification: ¶0529-0530). Therefore, Weikart in view of Groner and in further view of Dameron inherently discloses that the standard deviation of the heat transfer coefficient across a plurality of vials is less than 0.15 cals/cm2/°C with respect to claim 2, and that the vial, when subjected to an ink blot test, produces an ink blot that covers at least 60% of the footprint of the vial, with respect to claim 4. Please see MPEP §2112.
Regarding claim 3, Weikart in view of Groner and in further view of Dameron suggests the package of claim 1, and Weikart further discloses that the vial has a flat or substantially flat lower surface (Fig. 8).
Regarding claims 5-8, Weikart in view of Groner and in further view of Dameron suggests the package of claim 1. Weikart in view of Groner and in further view of Dameron do not explicitly disclose that the package is configured to maintain container closure integrity (CCI) when cycled between -20°C and 10°C, with respect to claim 5, in which during each cycle the package is held at both the lower temperature for 24 hours or more and at the upper temperature for 24 hours or more, with respect to claim 6, and in which the package is subject to at least three cycles, with respect to claim 7. However, Weikart further discloses that the vial may include a crimp in its closure (Fig. 8; ¶0046). The present specification indicates that such a configuration maintains CCI under the claimed conditions (Present specification: ¶0154 and 543). Therefore, Weikart in view of Groner and in further view of Dameron further suggests that the package is configured to maintain container closure integrity (CCI) when cycled between -20°C and 10°C, with respect to claim 5, in which during each cycle the package is held at both the lower temperature for 24 hours or more and at the upper temperature for 24 hours or more, with respect to claim 6, and in which the package is subject to at least three cycles, with respect to claim 7.
Regarding claims 8-12, Weikart in view of Groner and in further view of Dameron discloses the package of claim 1. Because Dameron teaches that both the Al2O3 and SiO2 layers in the bilayer gas barrier are deposited by ALD (Page 4576, col. 2, line 22 – Page 4577, col. 2, line 15), they consist essentially of a plurality of atomic monolayers pure Al2O3 and SiO2 respectively, as discussed in ¶0446 of the present specification. As discussed above, Dameron further teaches that an ALD Al2O3 may be protected from this corrosion by the deposition of an ALD SiO2 layer, forming alternating multilayer films of 26 nm Al2O3 and 60 nm SiO2, which also improves the gas barrier properties compared to the bare ALD Al2O3 films (Page 4573, Abstract; Page 4576, col. 2, line 22 – Page 4577, col. 2, line 15; Page 4578, section B). Because the multilayer films include multiple stacks of 26 nm Al2O3 and 60 nm SiO2, they include a layer of SiO2 beneath layers of Al2O3 and SiO2. Therefore, Weikart in view of Groner and in further view of Dameron further teaches that at least a portion of the gas barrier coating or layer consists essentially of a plurality of atomic monolayers of a pure element or compound, with respect to claim 8, that the gas barrier coating comprises a metal oxide, optionally Al2O3, with respect to claim 9, that the gas barrier coating comprises SiO2, with respect to claim 10, and that the gas barrier coating comprises multiple stacks of alternating layers of Al2O3 and SiO2, with respect to claim 12.
Regarding claims 13-16, Weikart in view of Groner and in further view of Dameron suggests the package of claim 8. Weikart further discloses that the gas barrier coating (Fig. 8, feat. 30) is supported by the interior surface of the wall (Fig. 8, feat. 16; ¶0240-0241), with respect to claim 13, that the package may have a pH protective layer between the lumen and the gas barrier coating (Fig. 8, feat. 34; ¶0240 and 0250-0274), that the pH protective coating comprises SiOxCy or SiNxCy, wherein x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3 (¶0250-0251), with respect to claim 15, and that the pH protective coating is deposited by PECVD (¶0250-0251), with respect to claim 16.
Regarding claim 17, Weikart in view of Groner and in further view of Dameron suggests the package of claim 16. Weikart is silent with respect to the dissolution rate of the pH protective coating per 44 hours of contact with a fluid composition having a pH between 5 and 9. However, the pH protective coating disclosed by Weikart (¶0250-0274) is structurally and compositionally identical to the claimed pH protective coating (Present Specification: ¶0020 and 0026-0031), and would therefore be expected to have the same properties. Please see MPEP §2112.01(II). Therefore, Weikart, and by extension Weikart in view of Groner and in further view of Dameron, inherently discloses that a fluid composition having a pH between 5 and 9 removes the pH protective coating or layer at a rate of 1 nm or less of pH protective coating or layer thickness per 44 hours of contact with the fluid composition. Please see MPEP §2112.
Regarding claims 18-20, Weikart in view of Groner and in further view of Dameron suggests the package of claim 1, and Weikart further discloses that the vial consists predominantly of a thermoplastic material selected from the following: PET, PETG, polypropylene, a polyamide, polystyrene, polycarbonate, TRITAN™, a cyclic block copolymer (CBC) resin, or a thermoplastic olefinic polymer, COP, COC, or any combination thereof (¶0159-0160 and 0193), with respect to claim 18, that the vial is COP (¶0159-0160 and 0193), with respect to claim 19, and that the vial has a volume of 10 mL or less (¶0118), with respect to claim 20.
Regarding claims 21-28, Weikart in view of Groner and in further view of Dameron suggests the package of claim 1, but is silent with respect to the increase in the moisture content of the lyophilized drug formulation, with respect to claims 21-22 and 25-26, or the residual moisture content of the lyophilized drug formulation after storage relative to the same formulation stored in a borosilicate glass vial, with respect to claims 23-24 and 27-28. However, as discussed above, Weikart in view of Groner and in further view of Dameron suggests a vial and gas barrier which is structurally and compositionally identical to the vial and gas barrier of the present application, and would therefore be expected to have the same properties. Please see MPEP §2112.01(II). The present application indicates that a vial with the gas barrier suggested by Weikart in view of Groner and in further view of Dameron would have the claimed residual moisture properties under the claimed conditions (Present application: ¶0778-0779 and 0784-0799). Therefore, Weikart in view of Groner and in further view of Dameron further inherently discloses that the residual moisture content of the lyophilized drug formulation increases by less than 0.4 wt. % after 60 days storage at room temperature and 75% relative humidity, with respect to claim 21, that the residual moisture content of the lyophilized drug formulation increases by less than 0.7 wt. % after 60 days storage at 40°C and 75% relative humidity, with respect to claim 22, that the residual moisture content of the lyophilized drug formulation after 60 days storage at room temperature and 75% relative humidity is equivalent or less than the residual moisture content of the same lyophilized drug formulation after 60 days storage in a borosilicate glass vial under the same conditions, with respect to claim 23, that the residual moisture content of the lyophilized drug formulation after 60 days storage at 40°C and 75% relative humidity is equivalent or less than the residual moisture content of the same lyophilized drug formulation after 60 days storage in a borosilicate glass vial under the same conditions, with respect to claim 24, the residual moisture content of the lyophilized drug formulation increases by less than 0.4 wt. % after 90 days storage at room temperature and 75% relative humidity, with respect to claim 25, that the residual moisture content of the lyophilized drug formulation increases by less than 1.2 wt. % after 60 days storage at 40°C and 75% relative humidity, with respect to claim 26, that the residual moisture content of the lyophilized drug formulation after 90 days storage at room temperature and 75% relative humidity is equivalent or less than the residual moisture content of the same lyophilized drug formulation after 90 days storage in a borosilicate glass vial under the same conditions, with respect to claim 27, and that the residual moisture content of the lyophilized drug formulation after 90 days storage at 40°C and 75% relative humidity is equivalent or less than the residual moisture content of the same lyophilized drug formulation after 90 days storage in a borosilicate glass vial under the same conditions, with respect to claim 28. Please see MPEP §2112.
Regarding claims 29-30, Weikart in view of Groner and in further view of Dameron suggests the package of claim 11, and Weikart further discloses that the gas barrier coating (Fig. 8, feat. 30) is supported by the interior surface of the wall (Fig. 8, feat. 16; ¶0240-0241) and further comprises a pH protective layer between the lumen and the gas barrier coating (Fig. 8, feat. 34; ¶0240 and 0250-0274), and that the pH protective coating is effective to prevent dissolution of the gas barrier layer (¶0250-0274). Weikart in view of Groner and in further view of Dameron are silent with respect to the Al2O3 layer, with respect to claim 29, and the SiO2, with respect to claim 30, being protected from dissolution under the claimed conditions. However, as discussed above, the vial, gas barrier, and pH protective coating suggested by Weikart in view of Groner and in further view of Dameron is structurally and compositionally identical to those of the present application, and would be expected to have the same properties. Please see MPEP §2112.01(II). The present application indicates that a vial with the gas barrier and pH protective coating suggested by Weikart in view of Groner and in further view of Dameron would have the claimed dissolution properties under the claimed conditions (Present specification: ¶0800-0807). Therefore, Weikart in view of Groner and in further view of Dameron further inherently discloses that the pH protective coating is effective to prevent dissolution of the Al2O3 barrier layer, with respect to claim 29, and to prevent dissolution of the SiO2 barrier layer, with respect to claim 30, such that the vial when filled with an aqueous solution of 50 mM potassium phosphate adjusted to a pH of 9.0, and incubated for 72 hours at any one or more of 4 °C, 25 °C, and 45 °C results in a solution containing less than 20 μg aluminum, with respect to claim 29, and less than 8 μg silicon, with respect to claim 30, as determined by ICP-OES.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARJUNA P CHATRATHI whose telephone number is (571)272-8063. The examiner can normally be reached M-F 8:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sarah Al-Hashimi can be reached at 5712727159. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ARJUNA P CHATRATHI/Examiner, Art Unit 3781
/SARAH AL HASHIMI/Supervisory Patent Examiner, Art Unit 3781