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 .
Priority
This Application claims the benefit of U.S. Provisional Application no. 63/343,143 filed May 18, 2022.
Claim Status
Claims 1-9 and 11-20 are pending and subject to examination.
Withdrawn Rejections – Overcome by Amendment
The rejection of claims 1-2, 6-9, 11-14 and 17-19 under 35 U.S.C. 102(a)(2) as being anticipated Bhadauria et al. (US20240165107A1, published May 23, 2024, effective filing date Mar. 16, 2021) is withdrawn.
The rejection of claims 1-2, 5-9, and 11-19 under 35 U.S.C. 102(a)(2) as being anticipated Bhadauria et al, (US20240165107A1, published May 23, 2024, effective filing date Mar. 16, 2021) citing to Benhabbor et al. (Nature Communications, volume 10, no. 4324 (2019), p. 1-12) to show an inherent disclosure is withdrawn.
The rejection of claims 1-9 and 11-19 under 35 U.S.C. 103 as being unpatentable over Bhadauria et al, (US20240165107A1, published May 23, 2024, effective filing date Mar. 16, 2021) citing to Benhabbor et al. (Nature Communications, volume 10, no. 4324 (2019), p. 1-12), as applied to claims 1-2, 5-9, and 11-19 above, and further in view of Hancock et al. (US20250017847A1, published January 16, 2025, effective filing date Sep. 30, 2021) is withdrawn.
The above rejections were overcome by the Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 102 – Previously Presented
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.”
The rejection of claim(s) 1-2, 5-6, 8, 11 and 13-20 under 35 U.S.C. 102(a)(2) as being anticipated by Rubnov et al. (US 20230293515 A1, published Sept. 21, 2023, effective filing date Mar. 17, 2022) (of record) is maintained.
Changing the statutory basis from 35 U.S.C. 103 to 35 U.S.C. 102 but relying on the same teachings does not constitute a new ground of rejection (MPEP 1207.03(a)).
Response to Arguments
The Applicant argues that Rubnov only teaches that the viscosity of the polymer is from 0.1 dl/g to 0.8 dl/g rather than from 0.1 dl/g to 0.6 dl/g (Remarks, p. 7-8). These arguments were fully considered but are not persuasive. As shown in the prior office action on page 9, Rubnov teaches a specific example, Formulation B, wherein the polymer has a viscosity of 0.4 to 0.6 dl/g, falling within the claimed range. Therefore, the claims remain anticipated by Rubnov.
Reiterated Rejection
Claim(s) 1-2, 5-6, 8, 11 and 13-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rubnov et al. (US 20230293515 A1, published Sept. 21, 2023, effective filing date Mar. 17, 2022).
Claim 1 is directed towards a pharmaceutical composition comprising:
Cariprazine, a pharmaceutically acceptable salt of cariprazine, or a mixture thereof;
A polymer comprising poly(lactic acid) (PLA), poly(lactide-co-glycolide) (PLGA), poly(glycolic acid) (PGA), or a combination thereof, wherein the polymer has a viscosity from 0.1 dl/g to 0.6 dl/g; and
A solvent.
Rubnov teaches a specific example of a pharmaceutical composition comprising cariprazine, a polymer comprising PLGA, wherein the polymer has a viscosity from 0.1 dl/g to 0.6 dl/g:
For example, Rubnov teaches dissolving the cariprazine in a solvent to create a solution and then mixing that solution with the polymer:
A Cariprazine depot formulation termed Formulation B was prepared using an ester terminated PLGA 75:25 having a viscosity of 0.4-0.6 dl/g, at 30% (w/w) concentration (total solvent). The formulation was prepared by dissolving the polymer in benzyl alcohol by continuous stirring at room temperature. Cariprazine hydrochloride and benzoic acid (3.7 molar equivalent of Cariprazine) were dissolved in benzyl alcohol. After complete dissolution, the Cariprazine solution was added to the polymer solution and stirred until a homogenous mixture was obtained.
Rubnov, Specification, ¶ 0138.
Therefore, claim 1 is anticipated.
Claim 2 is directed towards the pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable salt comprises cariprazine HCl. As shown above, Rubnov teaches cariprazine HCl. Therefore, claim 2 is anticipated.
Claim 5 is directed towards the pharmaceutical composition as claimed in claim 1, wherein the API has a weight ratio in the composition from 1% to 30%. The weight ratio of the API in Formulation B of Rubnov is 2.2% (Rubnov, Specification, ¶ 0139). Therefore, claim 5 is anticipated.
Claim 6 is directed towards the pharmaceutical composition of claim 1, wherein, in PLGA, lactide and glycolide have a ratio from 48:52 to 100:0. In Formulation B, the weight ratio is 75:25 (Rubnov, Specification, ¶ 0138). Therefore, claim 6 is anticipated.
Claim 8 is directed towards the pharmaceutical composition as in claim 1, wherein the polymer has a concentration in the pharmaceutical composition from 150 mg/mL to 1000 mg/mL.
The concentration of polymer in Formulation B of Rubnov is 30% or about 300 mg/mL (Rubnov, Specification, ¶ 0138). Therefore, claim 8 is anticipated.
Claim 11 is directed towards the pharmaceutical composition of claim 1, wherein the solvent comprises water miscible solvent or partially water miscible solvent. Claim 13 is directed towards the pharmaceutical composition of claim 11, wherein the partially water miscible solvent comprises benzyl alcohol (BA). As shown above, Rubnov teaches that the solvent comprises BA (Rubnov, Specification, ¶ 0138). Therefore, claims 11 and 13 are anticipated.
Claim 14 is directed towards the pharmaceutical composition of lcaim 1, wherein the API and the polymer have a weight ratio from 1:0.8 to 1:40. The weight ratio of API to polymer in Formulation B is about 3:40 (2.2:30). Therefore, claim 14 is anticipated.
Claim 15 is directed towards the pharmaceutical composition of claim 1, wherein the polymer and the solvent have a weight ratio from 1:0.5 to 1:4. The polymer and the solvent have a weight ratio of about 3:7 or 1:2.33, which falls within the claimed ratio. Therefore, claim 15 is anticipated.
Claim 16 is directed towards the pharmaceutical composition as claimed in claim 1, wherein the API, the polymer and the solvent have a weight ratio from 1:0.8:0.4 to 1:40:160. In formulation B, the weight ratio of the API, the polymer and the solvent is 2.2:30:70 which is abut 1:14:32, which falls within the claimed range. Therefore, claim 16 is anticipated.
Claim 17 is directed towards the pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a release percentage lower than 30% in the first 24 hours. Claim 18 is directed towards the pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a sustained release of more than 14 days. Formulation B of Rubnov has a release percentage lower than 30% in the first 24 hours and sustained release of more than 14 days:
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Rubnov, Specification, ¶ 0139.
Therefore, claims 17-18 are anticipated.
Claim 19 is directed towards the pharmaceutical composition of claim 1, wherein the pharmaceutical composition is stored at a temperature of 4°C to 25°C for use. The storage temperature before use is not further limiting to the structure of the composition and the composition of Rubnov meets the limitations of claim 1. Therefore, claim 19 is anticipated.
Claim 20 is directed towards a method for preparing a pharmaceutical composition, comprising: dispersing an active pharmaceutical ingredient (API) in a solvent to form a solution, wherein the API comprises cariprazine, a pharmaceutically acceptable salt of cariprazine, or a mixture thereof; and dissolving a polymer in the solution under continuous stirring, wherein the polymer comprises poly(lactic acid) (PLA), poly(lactide-co-glycolide) (PLGA),poly(glycolic acid) (PGA), or a combination thereof, and the polymer has a viscosity of 0.1 dl/g to 0.6 dl/g.
Rubnov teaches dissolving the cariprazine in a solvent to create a solution and then mixing that solution with the polymer:
A Cariprazine depot formulation termed Formulation B was prepared using an ester terminated PLGA 75:25 having a viscosity of 0.4-0.6 dl/g, at 30% (w/w) concentration (total solvent). The formulation was prepared by dissolving the polymer in benzyl alcohol by continuous stirring at room temperature. Cariprazine hydrochloride and benzoic acid (3.7 molar equivalent of Cariprazine) were dissolved in benzyl alcohol. After complete dissolution, the Cariprazine solution was added to the polymer solution and stirred until a homogenous mixture was obtained.
Rubnov, Specification, ¶ 0138.
Therefore, claim 20 is anticipated.
Claim Rejections - 35 USC § 102 – New Grounds of Rejection Necessitated by Amendment
Claim(s) 1-2, 5-6, 8-9, 11 and 13-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rubnov et al. (US 20230293515 A1, published Sept. 21, 2023, effective filing date Mar. 17, 2022).
The above rejection of claims 1-2, 5-6, 8, 11 and 13-20 under 35 U.S.C. 102(a)(2) as being anticipated by Rubnov et al. is incorporated herein by reference.
Claim 1 was amended to recite that the polymer has a viscosity from 0.1 dl/g to 0.6 dl/g, which is a new limitation.
Claim 1 is directed towards a pharmaceutical composition comprising:
Cariprazine, a pharmaceutically acceptable salt of cariprazine, or a mixture thereof;
A polymer comprising poly(lactic acid) (PLA), poly(lactide-co-glycolide) (PLGA), poly(glycolic acid) (PGA), or a combination thereof, wherein the polymer has a viscosity from 0.1 dl/g to 0.6 dl/g; and
A solvent.
Rubnov teaches a specific example of a pharmaceutical composition comprising cariprazine, a polymer comprising PLGA, wherein the polymer has a viscosity from 0.1 dl/g to 0.6 dl/g:
Claim 9 is directed towards the pharmaceutical composition of claim 1, wherein the polymer has a concentration in the pharmaceutical composition from 340 mg/mL to 560 mg/mL.
Rubnov teaches an exemplary pharmaceutical composition comprising cariprazine, a polymer comprising PLGA, wherein the polymer has a viscosity falling within 0.1 dl/g to 0.6 dl/g and the polymer has a concentration in the composition of 40% or about 400 mg/mL:
A Cariprazine depot formulation termed Formulation E was prepared as follows. An acid terminated PLGA 85:15 having a viscosity of 0.4-0.6 dl/g was mixed with an acid terminated PLGA 85:15 having a viscosity of 0.2-0.4 dl/g at a 2:1 ratio and 40% (w/w) concentration. The mixture of the polymers was dissolved in benzyl alcohol by continuous stirring at room temperature. Cariprazine hydrochloride (15% (w/w) polymer) was added to the polymer solution and stirred until complete dissolution was achieved and a homogeneous mixture was obtained.
Rubnov, Specification, ¶ 0149.
Therefore, claims 1 and 9 are anticipated.
Claim Rejections - 35 USC § 103- Previously Presented
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.”
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The rejection of claims 1-2, 5-8 and 10-20 under 35 U.S.C. 103 as being unpatentable over Rubnov et al. (US 20230293515 A1, published Sept. 21, 2023, effective filing date Mar. 17, 2022), as applied to claims 1-2, 5-6, 8, 11 and 13-20 above, and further in view of Bhadauria et al. (US20240165107A1, published May 23, 2024, effective filing date Mar. 16, 2021) is maintained.
Changing the order of references but relying on the same teachings does not constitute a new ground of rejection (MPEP 1207.03(a)).
Response to Arguments
The Applicant argues that Rubnov only teaches that the viscosity of the polymer is from 0.1 dl/g to 0.8 dl/g rather than from 0.1 dl/g to 0.6 dl/g (Remarks, p. 7-8). These arguments were fully considered but are not persuasive. As shown in the prior office action on page 9, Rubnov teaches a specific example wherein the polymer has a viscosity of 0.4 to 0.6 dl/g, falling within the claimed range. Therefore, the claimed range is not novel over the prior art.
Reiterated Rejection
Claims 1-2, 5-8 and 10-20 are rejected under 35 U.S.C. 103 as being unpatentable over Rubnov et al. (US 20230293515 A1, published Sept. 21, 2023, effective filing date Mar. 17, 2022), as applied to claims 1-2, 5-6, 8, 11 and 13-20 above, and further in view of Bhadauria et al, (US20240165107A1, published May 23, 2024, effective filing date Mar. 16, 2021) is maintained.
Claim 7 is directed towards the pharmaceutical composition as in claim 6, wherein the polymer comprises more than one PLGA with various ratios of lactide to glycolide. While Rubnov does not teach that the polymer comprises more than one PLGA with various ratios of lactide to glycolide, one of ordinary skill in the art would have a reasonable expectation of success to include more than one PLGA with various ratios of lactide to glycolide because similar compositions are commonly known in the art.
For example, Bhadauria teaches that the composition can comprise poly(lactic-co-glycolic acid) polymer and polylactic acid polymers (Bhadauria, Specification, ¶ 0208).
Bhadauria teaches a long acting injectable composition comprising cariprazine or its pharmaceutically acceptable salts thereof, and at least one rate controlling polymer comprising PLGA, and at least one solvent (Bhadauria, Specification, ¶ 0026). For example, Bhadauria teaches a specific example comprising cariprazine, PLGA/PLA and solvent:
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Bhadauria, Specification, ¶ 0212.
Therefore, claim 7 was prima facie obvious at the time of filing.
Claim 12 is directed towards the composition of claim 11, wherein the water miscible solvent comprises DMSO, NMP or a combination thereof.
As shown above, Rubnov specifically teaches that the solvent comprises benzyl alcohol. While Rubnov does not specifically teach that the solvent comprises DMSO, NMP or a combination thereof, one of ordinary skill in the art would have a reasonable expectation of success to use DMSO, NMP or a combination thereof as the solvent because similar compositions comprising DMSO, NMP or a combination thereof are commonly known in the art.
For example, Bhadauria teaches that the composition can comprise water miscible solvents such as DMSO and NMP and partially water miscible solvents such as benzyl alcohol:
In a further embodiment, the long acting injectable composition comprises cariprazine or its pharmaceutically acceptable salts thereof, at least one rate controlling polymer comprising poly(lactic-co-glycolic acid) polymer, sucrose acetate isobutyrate, triethyleneglycol poly(orthoester) polymer, and at least one solvent comprising 2-N-methyl pyrollidone, dimethyl acetamide, dimethyl sulfoxide, ethanol, glyceryl triacetate, wherein the said composition is an in-situ gelling composition
Bhadauria, Specification, ¶ 0026 (emphasis added);
In one embodiment, the long acting injectable composition comprises cariprazine or its pharmaceutically acceptable salts thereof, sesame oil and benzyl alcohol.
Bhadauria, Specification, ¶ 0045 (emphasis added);
Examples of preservatives, include, but are not limited to, benzyl alcohol, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), propyl gallate, methylparaben, propylparaben, tocopherols, and combinations thereof.
Bhadauria, Specification, ¶ 0084 (emphasis added).
Bhadauria teaches specific examples using NMP as the solvent:
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Bhadauria, Specification, ¶ 0197.
Therefore, claim 12 was prima facie obvious at the time of filing.
Claim Rejections - 35 USC § 103- New Grounds of Rejection Necessitated by Amendment
Claim(s) 1-6, 8-9, 11 and 13-20 are rejected under 35 U.S.C. 103 as being unpatentable over Rubnov et al. (US 20230293515 A1, published Sept. 21, 2023, effective filing date Mar. 17, 2022), as applied to claims 1-2, 5-6, 8-9, 11 and 13-20 above and further in view of Hancock et al. (US20250017847A1, published January 16, 2025, effective filing date Sep. 30, 2021) (of record).
The rejection of claims 1-2, 5-6, 8-9, 11 and 13-20 above as anticipated by Rubnov is incorporated herein by reference. As such, claims 1-2, 5-6, 8-9, 11 and 13-20 were prima facie obvious at the time of filing.
Claim 3 is directed towards the pharmaceutical composition of claim 2, wherein cariprazine and the pharmaceutically acceptable salt of cariprazine are present in a weight ratio from 1:99 to 99:1. Claim 4 is directed towards the pharmaceutical composition of claim 2, wherein cariprazine and the pharmaceutically acceptable salt of cariprazine are present in a weight ratio from 1:1 to 1:3.
Rubnov teaches that the composition may comprise cariprazine or a pharmaceutically acceptable salt thereof (e.g. Rubnov, Specification, ¶ 0013).
While Rubnov does not teach that the composition comprises a mixture of cariprazine free base and cariprazine hydrochloride in a weight ratio from 1:99 to 99:1 or 1:1 to 1:3, one of ordinary skill in the art would have a reasonable expectation of success to include a mixture of cariprazine free base and cariprazine hydrochloride in a weight ratio from 1:99 to 99:1 or 1:1 to 1:3 in a long acting injectable depot formulation because it is commonly known in the art to include the API as a free base: salt mixture in such ratios.
It is known in the art that a mixture of a drug's free base and salt form in a depot formulation is used to achieve a tailored, controlled-release profile. The free base and salt have different solubilities, allowing formulators to program the release rate. This is particularly useful for long-acting injectable depot products, such as in Rubnov and in the instant invention, which create a drug reservoir at the injection site to release medication over an extended period.
For example, Hancock teaches bupivacaine from implantable depots formulated with varying free base: salt ratios, such as 1:1 and 1:2 (free base: HCl), to have tailored drug release profiles:
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Hancock, Specification, ¶ 0271-0272.
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Hancock, Fig. 17.
Therefore, claims 3-4 were prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Conclusion
No claim is found to be allowable.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629