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 . Claims 1-11, 13-28 filed January 09, 2026 are currently pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/09/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of Claims
As indicated in the Office Action of 08/11/2025, claims 1-9 and 26-28 were withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Response to Amendment
Applicant’s amendments, filed 01/09/2026 are acknowledged. Claim 12 has been canceled in its entirety. Claim 10 is amended and is directed to a lyophilized pharmaceutical composition of phenobarbital sodium, prepared by a method according to claim 1, wherein the lyophilized pharmaceutical composition is suitable for intravenous administration upon reconstitution, and wherein the lyophilized pharmaceutical composition has a percent porosity in the range from about 20% to about 50%.
Applicant's arguments, filed 01/09/2026 have been fully considered. Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and objections presently being applied to the instant application.
Claim Rejections - 35 USC § 102-Rejection Maintained
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 19 remains rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kawada (Neonatal Care Vol. 22 pages 657-663 published 2009; machine translation provided).
Claim 19 is directed to a lyophilized pharmaceutical composition of phenobarbital sodium having one or more of :(a) a percent porosity in the range from about 20% to about 50%; (b) an ethanol content in the range from about 12000 ppm to about 25000 ppm; (c) total impurities in an amount of less than 0.2 % following 36 months of storage at about 200°C to about 250°C;(d) free of benzyl alcohol and propylene glycol; or (e) lyophilized phenobarbital sodium in an amount from 10 mg/vial to 100 mg/vial.
Applicant is reminded of MPEP 2113 wherein even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Kawada teaches preparation of lyophilized phenobarbital sodium pharmaceutical compositions for intravenous injection (NOBELBAR). Kawada teaches that said phenobarbital sodium composition is easily dissolved and reconstituted in sterile water for intravenous administration (page 9). Kawada teaches that said lyophilized phenobarbital sodium was developed to administer to neonates with seizures, as traditional phenobarbital sodium compositions contained 10% phenobarbital sodium for intramuscular or subcutaneous injection, or in doses of 50 mg to 200 mg (0.5 to 2 mL once), both of which were unsafe for infants (abstract, page 12). NOBELBAR comprises 250 mg of lyophilized phenobarbital sodium without any other excipients (Table). It comprises an osmotic pressure ratio of 2.5 to 2.6 when 1g is dissolved in 10 mL of water (Table). Regarding claim 19, Kawada teaches that the lyophilized phenobarbital sodium composition is free of additives and thus, is free of benzyl alcohol and propylene glycol.
Claim 19 remains rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sznitowska (Acta Poloniae Pharmaceutica Drug Research Vol. 62 pages 25-29 published 2005).
Applicant is reminded of MPEP 2113 wherein even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)
Sznitowska (Acta Poloniae Pharmaceutica Drug Research Vol. 62 pages 25-29 published 2005) teaches the preparation of lyophilized phenobarbital sodium pharmaceutical compositions. Sznitowska teaches dissolving mannitol and gelatine in water, followed by phenobarbital sodium (20 mg). The pH of the solution was 7.6-9.2. A stock solution of 2 mL was placed into the PVC blisters in the freeze-drier, followed by freezing at -45°C for 60 min, followed by warming to 20° C and 35 °C for 2 hours to arrive at the claimed lyophilized phenobarbital sodium composition. As shown in Table 1, the 20 mg phenobarbital sodium dissolved in a 2.0 mL solution reads on a concentration of 10 mg/mL (pages 25-26, Table 1). Regarding claim 19, Sznitowska teaches that the lyophilized pharmaceutical phenobarbital sodium composition is free of benzyl alcohol and propylene glycol (pages 25-26, Table 1).
Claim(s) 19 remains rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chodavarapu (US2021/0085608 published 03/25/2021).
Applicant is reminded of MPEP 2113 wherein even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Chodavarapu (US2021/0085608 published 03/25/2021) teaches the preparation of lyophilized phenobarbital sodium compositions with high purity (abstract). Chodavarapu teaches that stability of phenobarbital sodium is challenging as it readily hydrolyzes in water forming various degradation production ([0006]). Chodavarapu teaches that alpha-phenylbutyrylguanidine (PBG) is an art-recognized toxic impurity of said degradation and can cause severe side effects ([0006]). Chodavarapu teaches that said lyophilized phenobarbital sodium composition is stable for at least 15 months with no significant increase in the PBG impurity profile was observed ([0101]-[0103], Tables 2-3).
Regarding claim 19, Chodavarapu teaches preparation of lyophilized phenobarbital sodium compositions wherein said composition contains 100 mg per vial and teaches reconstitution of said lyophilized product in a concentration of 100 mg/mL ([0098]-[0101], [0105]). Chodavarapu teaches that said reconstituted lyophilized phenobarbital sodium composition comprises an osmolality of 158 mOsmol/Kg, ([0120], Table 9).
Applicant traverses. Applicant asserts that neither Kawada, Sznitowska nor Chodavarapu teach wherein the lyophilized pharmaceutical composition comprises a percent porosity in the range of from 20% to 50%.
Response to Arguments
Applicant’s arguments, filed 01/09/2026 are acknowledged and have been carefully considered. Regarding Applicant’s contention that neither Kawada, Sznitowska nor Chodavarapu teach wherein the lyophilized pharmaceutical composition comprises a percent porosity in the range of from 20% to 50%, this argument is unavailing. A percent porosity in the range of from 20% to 50% is not a structural requirement for the lyophilized phenobarbital sodium composition of claim 19 but rather one of 5 possible alternatives. Claim 19 is directed to a lyophilized pharmaceutical composition of phenobarbital sodium having one or more of :(a) a percent porosity in the range from about 20% to about 50%; (b) an ethanol content in the range from about 12000 ppm to about 25000 ppm; (c) total impurities in an amount of less than 0.2 % following 36 months of storage at about 200°C to about 250°C;(d) free of benzyl alcohol and propylene glycol; or (e) lyophilized phenobarbital sodium in an amount from 10 mg/vial to 100 mg/vial.
In the present case and as recited in the rejections of Kawada, Sznitowska nor Chodavarapu above, both Kawada and Sznitowska each teach that their respective lyophilized pharmaceutical phenobarbital sodium compositions are free of additives benzyl alcohol and propylene glycol, while Chodavarapu teaches preparation of lyophilized phenobarbital sodium compositions wherein said composition contains 100 mg per vial and teaches reconstitution of said lyophilized product in a concentration of 100 mg/mL ((Sznitowska: pages 25-26, Table 1; Chodavarapu: [0098]-[0101], [0105]). Each of the disclosed features read on options (d) or (e) of the required structural limitations of claim 19. Thus, the rejection of record is maintained for reasons of record.
NEW REJECTIONS NECESSITATED BY AMENDMENT
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.
Claim(s) 10-11, 15, 19, 21, 25 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Kawada (Neonatal Care Vol. 22 pages 657-663 published 2009; machine translation provided) and Courteille (U.S. 5,206,025 published 04/27/1993).
Claim interpretation is as follows: Claims 10-11 are directed to a lyophilized pharmaceutical composition of phenobarbital sodium, prepared by a method according to claim 1, wherein the lyophilized pharmaceutical composition is suitable for intravenous administration upon reconstitution, and wherein the lyophilized pharmaceutical composition has a percent porosity in the range from about 20% to about 50%.
Applicant is reminded of MPEP 2113 wherein even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Kawada teaches preparation of lyophilized phenobarbital sodium pharmaceutical compositions for intravenous injection (NOBELBAR). Kawada teaches that said lyophilized phenobarbital sodium was developed to administer to neonates with seizures, as traditional phenobarbital sodium compositions contained 10% phenobarbital sodium for intramuscular or subcutaneous injection, or in doses of 50 mg to 200 mg (0.5 to 2 mL once), both of which were unsafe for infants (abstract, page 12). NOBELBAR comprises 250 mg of lyophilized phenobarbital sodium without any other excipients (Table). It comprises an osmotic pressure ratio of 2.5 to 2.6 when 1g is dissolved in 10 mL of water (Table). Regarding the limitation of claim 15 and 19 wherein the phenobarbital is free from benzyl alcohol and propylene glycol, Kawada teaches that the lyophilized phenobarbital sodium composition is free of additives and thus, is free of benzyl alcohol and propylene glycol. Regarding claims 11, 21 and 25 Kawada teaches that said phenobarbital sodium composition is easily dissolved and reconstituted in sterile water for intravenous administration (page 9).
It is noted that Kawada does not specifically teach the percent porosity in the range of 20-50% in the lyophilized phenobarbital sodium composition.
Courteille (U.S. 5,206,025 published 04/27/1993) teaches preparation of porous, lyophilized phenobarbital compositions (col. 7 line 18-30, Example 9, claims 1, 6). Courteille teaches that freeze drying imparts a porous structure to the lyophilized phenobarbital composition, permitting a fast breaking up in water (col. 4 lines 45-50).
Applicant is reminded that properties, such as a percent porosity in the range of 20-50% that that accrue from a process step of lyophilizing phenobarbital sodium as taught in Kawada and Courteille above, are considered characteristic features of the claimed product. It is noted that MPEP 2112 and MPEP 2113 discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the Applicant to prove that subject matter shown to be in the prior art does not possess characteristics relied on or show an non-obvious difference.
In the present case the burden was shifted to Applicant to prove that lyophilized phenobarbital sodium composition of Kawada and Courteille does not comprise a percent porosity of 20-50%. Applicant has not provided objective evidence that the lyophilized phenobarbital sodium pharmaceutical composition for intravenous injection (NOBELBAR) does not inherently comprise a percent porosity of about 20% to about 50%.
Claim(s) 10-11, 14, 16-19, 20-23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Chodavarapu (US2021/0085608 published 03/25/2021) and Courteille (U.S. 5,206,025 published 04/27/1993).
Applicant is reminded of MPEP 2113 wherein even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Chodavarapu (US2021/0085608 published 03/25/2021) teaches the preparation of lyophilized phenobarbital sodium compositions with high purity (abstract). Chodavarapu teaches that stability of phenobarbital sodium is challenging as it readily hydrolyzes in water forming various degradation production ([0006]). Chodavarapu teaches that alpha-phenylbutyrylguanidine (PBG) is an art-recognized toxic impurity of said degradation and can cause severe side effects ([0006]). Regarding claim 14, Chodavarapu teaches that said lyophilized phenobarbital sodium composition is stable for at least 15 months with no detectable amount of PBG impurity profile was observed when reconstituted at 6 months at accelerated stability conditions which is equivalent to storage at 20°C for 24 months ([0101]-[0103], Tables 2-3).
Regarding claims 11, 16, 18-19 and 22, Chodavarapu teaches preparation of lyophilized phenobarbital sodium compositions wherein said composition contains 100 mg per vial and teaches reconstitution of said lyophilized product in a concentration of 100 mg/mL ([0093], [0098]-[0101], [0105]).
Regarding claim 23, Chodavarapu teaches that said reconstituted lyophilized phenobarbital sodium composition comprises an osmolality of 158 mOsmol/Kg, ([0120], Table 9).
It is noted that Chodavarapu does not specifically teach the percent porosity in the range of 20-50% in the lyophilized phenobarbital sodium composition.
Courteille (U.S. 5,206,025 published 04/27/1993) teaches preparation of porous, lyophilized phenobarbital compositions (col. 7 Example 9, claims 1, 6). Courteille teaches that freeze drying imparts a porous structure to the lyophilized phenobarbital composition, permitting a fast breaking up in water (col. 4 lines 45-50).
Regarding the claimed properties of a percent porosity in the range of 20-50%, or an impurity profile of less than 0.2% alpha-phenylbutyrylguanadine (PBG) after 36 months at 20°C (claims 14), Applicant is reminded that properties that that accrue from a process step of lyophilizing phenobarbital sodium as taught in Chodavarapu above are considered characteristic features of the claimed product. It is noted that MPEP 2112 and MPEP 2113 discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the Applicant to prove that subject matter shown to be in the prior art does not possess characteristics relied on or show an non-obvious difference.
In the present case the burden was shifted to Applicant to prove that lyophilized phenobarbital sodium composition of Chodavarapu and Courteille does not comprise a percent porosity of 20-50% and does not inherently comprise a percent porosity of about 20% to about 50%, nor does not inherently comprise less than 0.2% alpha-phenylbutyrylguanadine (PBG) after 36 months at 20°C
In the present, Applicant has not provided objective evidence that the lyophilized phenobarbital sodium pharmaceutical composition for intravenous injection of Chodavarapu does not inherently comprise a percent porosity of about 20% to about 50%, nor does not inherently comprise less than 0.2% alpha-phenylbutyrylguanadine (PBG) after 36 months at 20°C.
Secondly, regarding the limitation wherein the lyophilized phenobarbital sodium is present in an amount of 10 mg/vial (claim 17), it is noted that neither Chodavarapu nor Courteille teach wherein said porous lyophilized phenobarbital sodium is present in 10 mg per vial.
However, it is considered well within the capabilities of one of ordinary skill in the art to optimize the amount of porous lyophilized phenobarbital sodium in the vial to provide the optimal therapeutically effective amount of phenobarbital without having to either dilute the reconstituted solution or alternatively, use more than one vial to provide the required therapeutically effective dose. The amount of porous lyophilized phenobarbital sodium in the vial is a result effective parameter that will affect the physical properties of the final composition and is clearly a results effective parameter that a person of ordinary skill would routinely optimize, as disclosed in paragraphs [0025]-[0026] and [0127]-[0128[ of Chodavarapu. Optimization of amounts of lyophilized phenobarbital sodium in a vial is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, it would have been customary for an artisan of ordinary skill to determine the optimal amount of porous lyophilized phenobarbital sodium in the vial to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the composition and the criticality of the claimed amount of porous lyophilized phenobarbital sodium in the vial, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.")
Claim(s) 24 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Kawada (Neonatal Care Vol. 22 pages 657-663 published 2009; machine translation provided) and Courteille (U.S. 5,206,025 published 04/27/1993) as applied to claims 10-11, 15, 19, 21, 25 above, in view of Sznitowska (Acta Poloniae Pharmaceutica Drug Research Vol. 62 pages 25-29 published 2005).
As discussed above, the combination of Kawada and Courteille teaches preparation of lyophilized phenobarbital sodium pharmaceutical compositions for intravenous injection (NOBELBAR) free from benzyl alcohol and propylene glycol. Kawada teaches that said lyophilized phenobarbital sodium was developed to administer to neonates with seizures, as traditional phenobarbital sodium compositions contained 10% phenobarbital sodium for intramuscular or subcutaneous injection, or in doses of 50 mg to 200 mg (0.5 to 2 mL once), both of which were unsafe for infants (abstract, page 12). NOBELBAR comprises 250 mg of lyophilized phenobarbital sodium without any other excipients (Table). Regarding claims 11, 21 and 25, Kawada teaches that said phenobarbital sodium composition is easily dissolved and reconstituted in sterile water for intravenous administration, coupled with the knowledge that lyophilizing inherently imparts a porous structure to the lyophilized phenobarbital composition, permitting a fast breaking up in water (Kawada: page 9; Courteille: col. 4 lines 45-50, col. 7 line 18-30, Example 9, claims 1, 6).
The difference between the lyophilized phenobarbital sodium composition of embraced within the combined teachings of Kawada and Courteille and that of the present claims is that neither Kawada nor Courteille specifically teach wherein the lyophilized phenobarbital sodium pharmaceutical composition is prepared by (a) dissolving phenobarbital sodium in water to obtain a pre-lyophilized solution having a concentration between 10 mg/mL to 60 mg/mL of phenobarbital sodium and (b) lyophilizing the pre-lyophilized solution of step (a).
Sznitowska (Acta Poloniae Pharmaceutica Drug Research Vol. 62 pages 25-29 published 2005) teaches the preparation of lyophilized phenobarbital sodium pharmaceutical compositions. Sznitowska teaches dissolving mannitol and gelatine in water, followed by phenobarbital sodium (20 mg). The pH of the solution was 7.6-9.2. A stock solution of 2 mL was placed into the PVC blisters in the freeze-drier. As shown in Table 1, the 20 mg phenobarbital sodium dissolved in a 2.0 mL solution reads on a concentration of 10 mg/mL (pages 25-26, Table 1). Sznitowska further teaches lyophilizing said 10 mg/mL phenobarbital sodium solution at -45°C for 60 min, followed by warming to 20C° and 35 °C for 2 hours to arrive at the claimed lyophilized phenobarbital sodium composition.
Therefore, one of ordinary skill in the art of preparing porous lyophilized phenobarbital sodium compositions as taught Kawada and Courteille above, said skilled artisan would have found it prima facie obvious to prepare a pre-lyophilized solution of phenobarbital sodium in water wherein the concentration of phenobarbital sodium is at 10 mg/mL in view of Sznitowska, arriving at the claimed composition with a reasonable expectation of success.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, it was known in the prior art of Sznitowska to prepare dissolved aqueous solutions of phenobarbital sodium in a concentration of 10 mg/mL followed by lyophilizing said aqueous solutions of phenobarbital sodium. Consistent with this reasoning, it would have been obvious to have selected the dissolution of phenobarbital sodium in water at a concentration of 10 mg/mL followed by lyophilizing said 10 mg/mL solution from within the prior art of Sznitowska and apply it to the preparation of a porous lyophilized phenobarbital sodium compositions as taught Kawada and Courteille above, arriving at the claimed composition yielding no more than one would expect from such an arrangement.
Claim(s) 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Kawada (Neonatal Care Vol. 22 pages 657-663 published 2009; machine translation provided) and Courteille (U.S. 5,206,025 published 04/27/1993) as applied to claims 10-11, 15, 19, 21, 25 above, in view of Parker (U.S. Patent 9,901,576 published 02/27/2018) and Marek (Current Therapeutic Research Vol. 76 pages 90-97 published 2014).
As discussed above, Kawada teaches preparation of lyophilized phenobarbital sodium pharmaceutical compositions for intravenous injection (NOBELBAR) free from benzyl alcohol and propylene glycol. Kawada teaches that said lyophilized phenobarbital sodium was developed to administer to neonates with seizures, as traditional phenobarbital sodium compositions contained 10% phenobarbital sodium for intramuscular or subcutaneous injection, or in doses of 50 mg to 200 mg (0.5 to 2 mL once), both of which were unsafe for infants (abstract, page 12). NOBELBAR comprises 250 mg of lyophilized phenobarbital sodium without any other excipients (Table). Regarding claims 11, 21 and 25 Kawada teaches that said phenobarbital sodium composition is easily dissolved and reconstituted in sterile water for intravenous administration, coupled with the knowledge that freeze drying inherently imparts a porous structure to the lyophilized phenobarbital composition, permitting a fast breaking up in water (Kawada: page 9; Courteille: col. 4 lines 45-50, col. 7 line 18-30, Example 9, claims 1, 6).
The difference between the lyophilized phenobarbital sodium composition of embraced within the combined teachings of Kawada and Courteille and that of the present claims is that neither Kawada nor Courteille specifically teach wherein the lyophilized phenobarbital sodium pharmaceutical composition comprises an ethanol content of 12,000 to 25,000 ppm.
Parker (U.S. Patent 9,901,576 published 02/27/2018) teaches phenobarbital sodium injectable pharmaceutical compositions with a reduced impurity profile (col. 1 line 1-10). Parker teaches that ethanol is a suitable adjuvant to stabilize phenobarbital sodium when in solution (col. 3 lines 50-65).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to incorporate ethanol into the porous lyophilized phenobarbital sodium pharmaceutical compositions of Kawada and Courteille in view of Parker, as ethanol was art-recognized as stabilizing phenobarbital sodium pharmaceutical compositions.
However, the combination of Kawada, Courteille and Parker do not teach a concentration of 12,000 to 25,000 ppm ethanol.
Marek (Current Therapeutic Research Vol. 76 pages 90-97 published 2014) teaches that The American Academy of Pediatrics Committee on Drugs has recommended that the amount of ethanol contained in any preparation should not be able to produce a blood concentration of >25 mg/dL after a single dose, which corresponds to a concentration of 250 ppm ethanol.
Accordingly, one of ordinary skill in the art of preparing lyophilized phenobarbital sodium compositions in order to administer to neonatal patients as taught by Kawada, Courteille and Parker, said artisan would have found it prima facie obvious to incorporate ethanol into the phenobarbital sodium lyophilized composition in view of Parker as Parker teaches that ethanol is art-recognized as a stabilized for phenobarbital sodium compositions. Said artisan would have also found it prima facie obvious to limit the ethanol amount that would not produce a blood concentration of >25 mg/dL in view of Marek, as said ethanol concentration is the standard for American Academy of Pediatrics Committee on Drugs for the amount of ethanol contained in any drug preparation.
It is noted that the combination Kawada, Courteille, Parker and Marek does not specifically teach an ethanol concentration of 12,000 to 25,000 ppm in the lyophilized phenobarbital sodium composition. However, it is considered well within the capabilities of one of ordinary skill in the art to optimize the concentration of stabilizer ethanol in the lyophilized phenobarbital sodium composition to provide optimal stability for the active agent while limiting exposure of ethanol to neonatal patients upon administration. The concentration of ethanol in the lyophilized phenobarbital sodium composition is a result effective parameter that will affect the physical properties of the final composition. The concentration of ethanol in the lyophilized phenobarbital sodium composition is clearly a results effective parameter that a person of ordinary skill would routinely optimize. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, it would have been customary for an artisan of ordinary skill to determine the optimal concentration of ethanol in the lyophilized phenobarbital sodium composition to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the composition and the criticality of the claimed amounts, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.")
Lastly, regarding the limitation wherein the porous, lyophilized phenobarbital sodium composition of Kawada, Courteille, Parker and Marek comprises less than 0.2% impurities after 36 months at 20°C (claims 14), Applicant is reminded that properties that that accrue from a process step of lyophilizing phenobarbital sodium as taught in Kawada and Courteille above are considered characteristic features of the claimed product. It is noted that MPEP 2112 and MPEP 2113 discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the Applicant to prove that subject matter shown to be in the prior art does not possess characteristics relied on or show an non-obvious difference.
In the present case the burden is shifted to Applicant to prove that lyophilized phenobarbital sodium composition of Kawada, Courteille, Parker and Marek does not inherently comprise less than 0.2% impurities after 36 months at 20°C.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 10-11, 13-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8, 12-19, 21-25 of U.S. Patent No. 11,857,683 in view of Courteille (U.S. 5,206,025 published 04/27/1993).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following. Claim 1 of U.S. Patent 11,857,683 is directed to a lyophilized pharmaceutical composition comprising phenobarbital or its salts, with an ethanol concentration of 12,000 ppm to 50,000 ppm, wherein the amount of impurities does not exceed 0.2% following 36 months of storage at 20-25°C, and wherein the lyophilized pharmaceutical composition is free of benzyl alcohol and propylene glycol. The composition of claim 1 of U.S Patent 11,857,683 overlaps with the subject matter embraced within claims 10, 11, 13-15, 19. Claim 12 of U.S. Patent 11,857,683 is directed to the reconstituted lyophilized phenobarbital composition of claim 1, while claims 13-20 overlap with the osmolality and concentration of phenobarbital found in present claims 19, 21-23.
The difference between the claimed lyophilized phenobarbital sodium composition of claims 1-4, 8, 12-19, 21-25 of U.S. Patent No. 11,857,683 and the present claims is that the claimed lyophilized phenobarbital sodium composition of claims 1-4, 8, 12-19, 21-25 of U.S. Patent No. 11,857,683 do not specifically teach wherein the porosity of the lyophilized phenobarbital sodium composition is from 20% to about 50%.
Courteille (U.S. 5,206,025 published 04/27/1993) teaches preparation of porous, lyophilized phenobarbital compositions (col. 7 line 18-30, Example 9, claims 1, 6). Courteille teaches that freeze drying imparts a porous structure to the lyophilized phenobarbital composition, permitting a fast breaking up in water (col. 4 lines 45-50).
Applicant is reminded that properties, such as a percent porosity in the range of 20-50% that that accrue from a process step of lyophilizing phenobarbital sodium as taught in claims 1-4, 8, 12-19, 21-25 of U.S. Patent No. 11,857,683 and Courteille above, are considered characteristic features of the claimed product. It is noted that MPEP 2112 and MPEP 2113 discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the Applicant to prove that subject matter shown to be in the prior art does not possess characteristics relied on or show an non-obvious difference.
In the present case the burden was shifted to Applicant to prove that lyophilized phenobarbital sodium composition of claims 1-4, 8, 12-19, 21-25 of U.S. Patent No. 11,857,683 and Courteille does not inherently comprise a percent porosity of 20-50%. However, Applicant has not provided objective evidence that the lyophilized phenobarbital sodium pharmaceutical composition for intravenous injection embodied within claims 1-4, 8, 12-19, 21-25 of U.S. Patent No. 11,857,683 does not inherently comprise a percent porosity of about 20% to about 50%.
Conclusion
In view of the rejections set forth above, no claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W KOSTURKO whose telephone number is (571)270-5903. The examiner can normally be reached M-F 9:00-5:30.
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, CLINTON A BROOKS can be reached at 571-270-7682. 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.
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621