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 .
Status of Application
The Amendments and Remarks filed on 12/31/25 are acknowledged.
Claims 2 and 5 were cancelled.
Claims 1, 9, and 14-16 were amended.
Claims 1, 3-4, and 6-21 are pending.
Response to Amendments/Arguments
Claim Rejections - 35 USC § 112
Applicant amended claim 15 to remove the term “prevention.” In light of this amendment, the rejection of claim 15 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the scope of enablement requirement, is withdrawn.
Claim Interpretation
Applicant’s amendment of claim 14 to recite “to a patient in need thereof” is acknowledged.
Claim Rejections - 35 USC § 102
In light of the cancellation of claim 5, the rejection of this claim under 35 U.S.C. 102(a)(1) as being anticipated by Pullagurla et al. (US 2019/0160005 A1 – “Pullagurla”) is moot.
Notice for all US Patent Applications filed on or after March 16, 2013
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 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.
Maintained Rejections
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 of this title, 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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 1, 3-4 and 6-21 are again rejected under 35 U.S.C. 103 as being unpatentable over Pullagurla et al. (US 2019/0160005 A1 – “Pullagurla”) in view of Watkins (US 2019/0224322 A1) and Yamashita et al. (US 2015/0087655 A1 – “Yamashita”).
Instant claim 1 is drawn to an amorphous form comprising 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1 H-quinolin-2-one and at least one organic acid, wherein the organic acid is a carboxylic acid with 1 to 8 carbon atoms.
Pullagurla discloses a method for producing a solid dispersion containing brexpiprazole (7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1 H-quinolin-2-one) as an active pharmaceutical ingredient (API) (Abstract, claims 1-2). Example 56 discloses the preparation of a solid dispersion of brexpiprazole with hydroxypropyl methylcellulose (HPMC) ([0176]). Example 60 discloses the preparation of a solid dispersion of brexpiprazole with hydroxypropyl cellulose (HPC) ([0180]). Example 68 discloses the preparation of a solid dispersion of brexpiprazole with polyvinylpyrrolidone K-30 (PVP-K30) ([0188]). The solid dispersions are produced by using spray drying ([0069], [0094]-[0096]). The solid dispersion is amorphous ([0020]).
Pullagurla does not expressly teach at least one organic acid.
Watkins teaches a composition comprising a therapeutic agent and an organic acid (Abstract, claim 1). The therapeutic agent is brexpiprazole ([0014], [0091], and claim 8). Watkins teaches that many insoluble drugs are weak organic bases and their water solubility improves upon protonation, i.e., when they are converted into a salt ([0003]). The therapeutic agent is solubilized through the use of partially soluble organic acids to improve delivery of the therapeutic agent from a drug delivery platform for a sustained period of time ([0084]).
Yamashita teaches a process of producing a dihydrate of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1 H-quinolin-2-one or brexpiprazole by mixing with at least one organic acid selected from the group consisting of acetic acid and lactic acid ([0034], [0035], Example 1 – [0147], Example 3 – [0163], and claim 7).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a solid dispersion containing brexpiprazole with HPMC, HPC, or PVP-K30, as taught by Pullagurla, in view of the composition comprising brexpiprazole and an organic acid, as taught by Watkins, and the production of a dihydrate of brexpiprazole by mixing with at least one organic acid selected from the group consisting of acetic acid and lactic acid, as taught by Yamashita, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because all the references teach compositions comprising brexpiprazole, Pullagurla teaches that increasing solubility enhances the bioavailability of the API ([0074]), and Watkins teaches that solubility of drugs improves upon protonation, i.e., when they are converted into a salt ([0003]), and that the therapeutic agent is solubilized through the use of partially soluble organic acids to improve delivery of the therapeutic agent from a drug delivery platform for a sustained period of time ([0084]).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding instant claim 1, the limitation of an amorphous form would have been obvious over the amorphous solid dispersion ([0020]), as taught by Pullagurla.
Regarding instant claim 1, the limitation of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1 H-quinolin-2-one would have been obvious over the brexpiprazole (7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1 H-quinolin-2-one) as an active pharmaceutical ingredient (API) (Abstract, claims 1-2), as taught by Pullagurla, the brexpiprazole ([0014], [0091], and claim 8), as taught by Watkins, and the brexpiprazole (Example 1 –[0147], Example 3 – [0163], and claim 7), as taught by Yamashita.
Regarding instant claims 1 and 3, the limitations of at least one organic acid that is a carboxylic acid with 1 to 8 carbon atoms would have been obvious over the organic acid (Abstract, claim 1), as taught by Watkins, and the acetic acid and lactic acid ([0026], [0035], Example 1 –[0147], Example 3 – [0163], and claim 7), as taught by Yamashita.
Regarding instant claims 4, 6, and 7, the limitations of the enteric polymer would have been obvious over the HPMC ([0176]), as taught by Pullagurla.
Regarding instant claims 8 and 21, the limitations of the spray dried powder would have been obvious over the solid dispersions produced by using spray drying ([0069], [0094]-[0096]), as taught by Pullagurla.
Regarding instant claims 9 and 16, the limitations of the method for producing the amorphous form of claim 1 would have been obvious over the method of preparing the solid dispersions by using spray drying ([0069], [0094]-[0096]), as taught by Pullagurla. The limitation of the active would have been obvious over the brexpiprazole (Abstract, claims 1-2), as taught by Pullagurla, Watkins ([0014], [0091], and claim 8), and Yamashita (Example 1 –[0147], Example 3 – [0163], and claim 7). The limitation of an enteric polymer would have been obvious over the HPMC ([0176]), as taught by Pullagurla. The limitation of an organic acid would have been obvious over the organic acid (Abstract, claim 1), as taught by Watkins, and the acetic acid and lactic acid ([0026], [0035], Example 1 –[0147], Example 3 – [0163], and claim 7), as taught by Yamashita.
Regarding instant claims 10, 12, 17, and 19, the limitations of a pharmaceutical composition comprising the amorphous form of claim 1 and an oral solid pharmaceutical composition, respectively, would have been obvious over the powder, tablet or film ([0051]), as taught by Watkins, and the tablets, pills, powders, etc. ([0116]), as taught by Yamashita.
Regarding instant claims 10, 11, 17, and 18, the limitations of a hydrophilic polymer would have been obvious over the celluloses or cellulose derivatives, vinyl pyrrolidone polymers and copolymers comprising polyvinyl alcohol, polyvinylpyrrolidone ([0073]), as taught by Pullagurla.
Regarding instant claims 13 and 20, the limitations of “after oral administration of the pharmaceutical composition to a human, the steady-state blood concentration of the 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1 H-quinolin-2-one is maintained within the range of 15 ng/ml to 400 ng/ml for 1 week” is a future intended effect that does not impart patentability to the pharmaceutical composition since the same composition is taught in the form of a powder, tablet or film ([0051]), by Watkins, and the tablets, pills, powders, etc. ([0116]), by Yamashita.
Regarding instant claim 14, the limitation of a method of using the pharmaceutical composition according to claim 9 comprising administering the active ingredient at a dose of 5 mg to 60 mg once a week would have been obvious over the dosage of the active ingredient in pharmaceutical preparation of about 1 to 200 mg ([0125]), as taught by Yamashita, unless there is evidence of criticality or unexpected results.
Regarding instant claim 15, the limitation of the treatment of central neurological disease would have been obvious over the treatment of a disease of the central nervous system ([0091] and [0137]), as taught by Watkins, and the treatment of central nervous system diseases including schizophrenia, psychotic disorder, mood disorder, bipolar disorder, etc. ([0126]), as taught by Yamashita.
Response to Arguments
Applicant’s arguments (Pages 7-10, filed 12/31/25) with respect to the rejection of claims 1, 3-4, and 6-21 under 35 USC § 103 as being unpatentable over Pullagurla in view of Watkins and Yamashita have been fully considered but are not persuasive.
Applicant argues that: “Based on the claim language and Applicant’s specification, the amorphous form of the present disclosure is not intended to form a salt of brexpiprazole, but is directed to an amorphous form of a mixture of brexpiprazole and an organic acid. As the Office admits, Pullagurla nowhere discloses or suggests organic acids. Id. at 9 (explaining that "Pullagurla does not expressly teach at least one organic acid."). Additionally, Watkins and Yamashita teach merely organic acids for salts of brexpiprazole. Id. Thus, the cited references fail to teach and/or suggest the amorphous form of a mixture of brexpiprazole and an organic acid, as recited in the claimed subject matter. Pullagurla, Watkins, and Yamashita fail to teach all the claim elements” (emphasis original).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a mixture of brexpiprazole and an organic acid, or an amorphous dispersion comprising a mixture of brexpiprazole and an organic acid) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Instant claim 1 does not recite a mixture of brexpiprazole and an organic acid, or an amorphous dispersion comprising a mixture of brexpiprazole and an organic acid. Instant claim 1 recites “An amorphous form comprising 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1 H-quinolin-2-one and at least one organic acid, wherein the organic acid is a carboxylic acid with 1 to 8 carbon atoms.”
Applicant argues that the amorphous form (an amorphous form containing brexpiprazole and an organic acid) of the claimed subject matter would not have been obvious, as there is no teaching in any references directed to the amorphous form of a mixture of brexpiprazole and an organic acid.
This is not persuasive because the limitation of an amorphous form would have been obvious over the amorphous solid dispersion ([0020]), as taught by Pullagurla. The limitation of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1 H-quinolin-2-one would have been obvious over the brexpiprazole (7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1 H-quinolin-2-one) as an active pharmaceutical ingredient (API) (Abstract, claims 1-2), as taught by Pullagurla, the brexpiprazole ([0014], [0091], and claim 8), as taught by Watkins, and the brexpiprazole (Example 1 –[0147], Example 3 – [0163], and claim 7), as taught by Yamashita. The limitations of at least one organic acid, wherein the organic acid is a carboxylic acid with 1 to 8 carbon atoms would have been obvious over the organic acid (Abstract, claim 1), as taught by Watkins, and the acetic acid and lactic acid ([0026], [0035], Example 1 –[0147], Example 3 – [0163], and claim 7), as taught by Yamashita. All the claimed components in the same arrangement of a solid amorphous dispersion are taught by the prior art. The claimed invention would have been obvious over the combined teachings of Pullagurla, Watkins, and Yamashita.
Therefore, the rejection of 10/01/25 is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARADHANA SASAN whose telephone number is (571)272-9022. The examiner can normally be reached Monday to Friday from 6:30 am to 3:00 pm.
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/ARADHANA SASAN/Primary Examiner, Art Unit 1615