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 .
DETAILED ACTION
Claims 52-72 are pending and are under consideration in the instant office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/7/2023 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
Priority
This application is a U.S. National phase application under 35 U.S.C 371 of PCT application PCT/IN2022/050242, filed 3/15/2022, which claims benefit under Title 35 U.S.C 119 to Indian patent application no. 07117274.6 filed on 03/16/2021. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 52-72 are rejected under 35 U.S.C. 103(a) as being unpatentable over by Lupin (IN 201721043173, Cited in IDS dated 11/7/2023) and Hui et al. (US 2021/0177768, priority date 12/13/2019) in view of Kulkarni et al. (WO 2018/015915, cited in instant IDS).
Instant claims 52-60 are drawn to a long acting injectable composition comprising cariprazine or its pharmaceutically acceptable salts thereof, a suspending agent, a buffer, and vehicle, wherein the injectable composition is in the form of an aqueous suspension.
Instant claims 61-68 are drawn to a long acting injectable composition comprising cariprazine or its pharmaceutically acceptable salts thereof, a rate controlling polymer, and solvent, wherein the injectable composition forms an in-situ gel upon injection.
Instant claims 69-72 are drawn to a long acting injectable composition comprising cariprazine or its pharmaceutically acceptable salts thereof, cariprazine or its pharmaceutically acceptable salts thereof, a rate controlling polymer, and solvent, wherein the injectable composition is in the form of microsphere.
Lupin disclose an injectable pharmaceutical composition comprising Cariprazine, its salts , esters and solvates in the form of aqueous suspension (abstract, page 13, lines 30-35). Lupin discloses that hat the pharmaceutical composition comprising of suspending agent is selected from polyvinylpyrrolidones, gums, cellulose derivatives (including hydroxypropyl methylcellulose, hydroxypropy1 cellulose, hydroxyethyl cellulose, microcrystalline cellulose, and others), polymers of carboxymethy1 celluloses, cyclodextrins, gelatin, hypromellose phthalates, cellulose acetate phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, polyethylene glycols, polyethylene oxides, polyvinyl alcohols (see page 13, lines 1-14). Further, Lupin discloses that the injectable composition comprises dibasic calcium phosphate (see page 16, lines 11-15); the tonicity adjusting agent is selected from mannitol, sucrose, lactose, maltose, xylitol, glucose, and sorbitol (see page 6, lines 28-32); stabilizer is selected from butylated hydroxytoluene, butylated hydroxy anisole, propyl gallate, and -tocopherol (see page 7, lines 31 33). Furthermore, Lupin discloses that the injectable composition comprises polymeric binder for control release rate including but not limited to polyethylene glycol, hydroxypropy1 methylcellulose, polyvinyl pyrrolidone, hydroxypropy1 cellulose, sodium alginate, gelatin, ethyl cellulose, methylcellulose, starch, pectin, chitosan (see page 16, lines 11-17; page 14, lines 18-21) and the solvent is selected from N-methyl pyrrolidone, methylene dichloride, ethylene dichloride, methyl acetate, ethyl acetate, acetonitrile, methanol, ethanol, isopropyl alcohol and combinations thereof (see page 11, lines 24-31).
Hui et al. discloses long-term injectable formulations and delivery systems of cariprazine (abstract). They disclose their compositions to included sustained release microparitcles and nanoparticles in which carprazine is incorporated [0058] . They teach cariprazine with a biodegradable and biocompatible polymer selected from the group poly(lactic) acid, poly(glycolic) acid, copolymers of the foregoing, poly(aliphatic carboxylic acids), copolyoxalates, polycaprolactone, polydioxonone, poly(ortho carbonates), poly(acetals), poly(lactic acid-caprolactone), polyorthoesters, poly(glycolic acid-caprolactone), polyanhydrides, albumin, casein, lipids, and waxes and non-ionic water soluble colloid is selected from the group consisting of one or more of poly(vinyl alcohol), polysorbate, lecithin, carboxymethyl cellulose, gelatin, poly(vinyl pyrrolidone), Tween 80, Tween 20, or Span. And, often the non-ionic water soluble colloid is selected from the group consisting of one or more of poly(vinyl alcohol), polysorbate, lecithin, carboxymethyl cellulose, gelatin, poly(vinyl pyrrolidone), Tween 80, Tween 20, or Span [0012]. The amount of Cariprazine in their inventive microparticles ranged from about 20-50% by weight [00369]. They also disclose that the most preferred polymer for use in their invention is the copolymer of poly (d,l, lactide0co-glycolide) [0033], In Example 6 Hui et al. discloses preparation of cariprazine microparticles with 70 mg of PLGA (50:50) polymers and 30. mg of cariprazine. [0067].
The difference between Lupin and Hui et al. and the subject matter of the present claims is that they fail to disclose the injectable composition of cariprazine in which forms an in-situ gel upon injection.
Kulkarni et al , moreover discloses an injectable composition of cariprazine in the dosage form of in-situ gelling technology comprising of one or more pharmaceutically acceptable excipient (s), one or more solvents/cosolvents, preservatives, buffering agents, pH adjusting agents, and using one or more rate-controlling polymers selected from polylactides, polyglycolide, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyorthoesters, polycarbonates, polyamides and copolymers, and combinations thereof (see claims 1, 10, 11).
The differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains because it would have been prima facie obvious to the skilled artisan. As such it would have been prima facia obvious to a person of ordinary skill in the art to arrive at the instant claims motivated and guided by the combined teachings of Lupin, Hui and Kulkarni et al. An ordinarily skilled artisan would be motivated from the references above to formulate a long acting injectable with cariprazine as these compositions are well known in the art and the excipients used in the preparation of such agents and the procedures are also well taught in the art before the date of this application. Absence of evidence to the contrary, Selection of excipients and the amounts to be used can be readily determined by one of ordinary skilled in the arts based upon experience and consideration of standard procedures and reference work in the field. It is recognized that pharmaceutical excipients may perform more than one function, and are therefore characterized as having different uses depending on the particular application. While the use of an excipient in the context of a particular formulation may determine the function of the excipient, the inclusion of any particular excipient into any one or more category as set forth above is not meant to limit the function of that excipient.
.With regards to instant claims 53-60 ,62, 64-68, Hui et al. discloses preparation of Hui et al. discloses preparation of cariprazine microparticles with 70 mg of PLGA (50:50) polymers and 30. mg of cariprazine. [0067] therefore giving a starting concentrations of cariprazine and the polymer to be used in the long acting injection composition. With regards to the buffer concentration recited in claim 55, it would be obvious to a person of ordinary skill in the art to determine this concentration so as to achieve a specific pH of the solution. As such optimization of the concentration of each of the excipients would be obvious to a person of ordinary skill in the art. It is noted that "[W]here 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).
As such a person of ordinary skill in the art would be imbued with a reasonable expectation of success in formulating a long acting injectable cariprazine formulation as claimed.
Conclusion
Claims 52-72 are rejected. No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7 am to 4 pm..
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/SAVITHA M RAO/Primary Examiner, Art Unit 1691