DETAILED ACTION
Claims
Acknowledgement is made of the remarks/amendments 12/8/2026. Claims 1-11, 13-14, 18-19 and 21-26 are pending in the instant Office action. Claims 1, 7-9, 11, 13-14 and 18-19 were amended. Claims 12, 15-17 and 20 were cancelled. Claims 21-26 were newly added.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
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 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 1-11, 13-14, 18-19 and 21-26 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (WO 2020/156437, published Aug. 6, 2020, filed Jan. 22, 2020 with an effectively filed date to foreign priority CN201910084801.3 filed Jan. 29, 2019, as per Applicant’s IDS – translated by US2022/0144821 – the PGPub of the US 371 entry of this WO application) in view of Sekhon BS (Pharmaceutical co-crystals – a review, ARS Pharmaceutica, 2009, 50(3), 99-117).
Ma et al. teach AKT inhibitors of generic formula (I) and their use in treating AKT mediated diseases including prostate cancer among others (abstract, [0004], claim 22) relevant to method claims 18-19 and 24-25. More specifically Ma et al. teach compound 15, isomer 2 which is the parent compound of instant claim 1 (p. 43, top). The compound is initially purified by pouring into ice water and extraction with ethyl acetate which suggest the compound is poorly water soluble or such an extraction would not be possible. It is isolated as a pale yellow liquic. This compound is isolated via crystallization as the oxalate isopropanol complex ([0217], Fig. 2).
The teachings of Ma et al. differ from the instant claims in that the crystal formed is the oxalate isopropanol and not the fumarate hydrate.
Sekhon BS teaches that the formation of co-crystals is considered to be a better alternative to optimizing drug properties of pharmaceutical materials – co-crystals can be utilized to address issues such as solubility, stability and bioavailability without changing the chemical composition of the API (abstract, p. 101). Sekhon BS teach that co-crystals can be prepared from two molecules of any shape or size having complementary hydrogen bond functionalities and can be formed by a number of techniques including slow solvent evaporation, slurrying, solvent-drop grinding, co-sublimation etc. (p. 103). The nitrogen and carbonyl oxygen molecules of the parent compound claimed are all hydrogen bond acceptors, with the -NH amino moieties being hydrogen bond donors. Fumaric acid has both hydrogen bond donating and accepting properties. Reference 67 recognizes that co-crystal hydrates can be formed via neat and liquid-assisted grinding. Sekhon BS teaches that the formation of salts vs. co-crystals is a matter of pka and that pyridine and 4-dimethylaminopyridine each are capable of forming a co-crystal with fumaric acid. Fumaric acid is also known to form stable solid forms of tiotropium.
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have formulated crystalline compound 15, isomer 2 as the fumarate hydrate with a reasonable expectation of success. One would have been motivated to do so as fumarate co-crystals are a known technique for optimizing drug properties of pharmaceutical materials and compound 15, isomer 2 is known in its native state to be a yellow liquid and poorly water soluble but not reactive in water as evidenced by the fact that water is used as a work-up solvent – both poor solubility and a liquid state are physical properties which are undesirable for pharmaceutical materials (Sekhon BS abstract). Further the act of solvent drop grinding and co-sublimation are well-known means of forming co-crystals. Regarding the specific crystal form A of the fumarate hydrate, it does not appear that the fumarate hydrate forms any other forms so because it would have been obvious to formulate the fumarate hydrate co-crystal it only follows that it would form as crystal form A. Evidence supporting this position can be found in the instant specification which shows that different crystallization techniques (co-sublimation and seeding) both yield crystal form A. There is no evidence suggesting that any other forms are possible for the fumarate hydrate.
Response to Arguments
Applicant argues that Ma et al. WO 2020/156437 is disqualified as prior art under the 35 USC 102(b)(2)(C) exception (arguments p. 8). This argument is not persuasive for 2 reasons.
Ma et al. qualifies as art under both 35 USC 102(a)(1) by the publication date, and under 35 USC 102(a)(2) by the filing date. The 102(b)(2)(C) exception can only be used to overcome 102(a)(2) art.
The instant application has a 371 PCT date of 7/22/2021, and claims benefit to a CN application filed 7/22/2020 – however the application does not receive this benefit until/unless a certified translation is provided.
Ma et al. WO 2020/156437 was published 8/6/2020 and filed 1/22/2020 and claims benefit to a CN application filed 1/29/2019. Ma et al. qualifies as art under both 102(a)(1) and 102(a)(2).
The statement that attempts to disqualify Ma et al. under 102(b)(2)(C) is not proper – it utilizes the old pre-AIA language. The language required by 102(b)(2)(C) is rather specific – it does not talk about the application and the reference being co-owned. It requires that the subject matter disclosed and the claimed invention be co-owned. See MPEP 2154.02(c), last paragraph.
In conclusion, even if the proper 102(b)(2)(C) statement can be made, Ma et al. still qualifies as art under 35 USC 102(a)(1). A certified translation could be used to exclude Ma et al. from being prior art.
Applicant argues there’s no technical driving force for improving the oxalate-isopropanol crystal by replacing the salt form or changing the crystal state and there’s no motivation to combine the references. These arguments (pp. 8-10) have been fully considered but are not persuasive. The examiner maintains that a prima facie case has been presented. The facts at hand here are akin to those of Pfizer v. Apotex in MPEP 2143(I)(E), Example 1 (obvious to try). To reiterate, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have formulated crystalline compound 15, isomer 2 as the fumarate hydrate with a reasonable expectation of success. One would have been motivated to do so as fumarate co-crystals are a known technique for optimizing drug properties of pharmaceutical materials and compound 15, isomer 2 is known in its native state to be a yellow liquid and poorly water soluble but not reactive in water as evidenced by the fact that water is used as a work-up solvent – both poor solubility and a liquid state are physical properties which are undesirable for pharmaceutical materials (Sekhon BS abstract). Regarding the specific crystal form A of the fumarate hydrate, it does not appear that the fumarate hydrate forms any other forms so because it would have been obvious to formulate the fumarate hydrate co-crystal it only follows that it would form as crystal form A. There is no evidence suggesting that any other forms are possible for the fumarate hydrate.
Applicant argues the present application achieves unexpected results.
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This argument is not persuasive. MPEP 716.02(b) instructs that the evidence relied upon should establish “that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance.” There is no evidence regarding what the person of ordinary skill in the art would have expected about the differences in these crystal forms. An improvement is not automatically surprising. There is no evidence that the difference in stability is statistically and practically significant. The difference between 99.66% at 60 degrees C and 7 days is 0.3% different from the starting point for the oxalate-isopropanol. And the difference between 99.88 and 99.84 is 0.04% different at 60 degrees C and 20d for the fumarate hydrate. It is hard to compare the results because the line between the 2 data points in each study is essentially flat. There’s no reason to assume the stability of the oxalate-isopropanol will dive off after 7 days. 99.66% stability appears to be a practical stability.
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 1-11, 13-14, 18-19 and 21-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of US 12617784 (granting from 17/426047); over claims 1-9, 14, and 17 of 18/017422; over claims 1-11, 15, 17, 19, 20-26 of 18/017416, notice of allowance mailed 5/6/2026 (reference application/patent) each in view of Sekhon BS (Pharmaceutical co-crystals – a review, ARS Pharmaceutica, 2009, 50(3), 99-117). Although the claims at issue are not identical, they are not patentably distinct from each other because each of the copending applications is directed to AKT inhibitors and methods for preventing and/or treating AKT mediated diseases or conditions including prostate cancer.
More specifically, the claims of patent ‘784 are directed to a generic compound of formula I (claim 1) that encompasses the parent compound of the instant claims. Claim 11 has a number of compounds, one of which is the parent compound of the instant claims.
More specifically, copending ‘422 is directed to a pharmaceutically acceptable salt which salt is a fumarate among others (claim 1, claim 2 is directed to the fumarate or HCl salt with claim 6 being directed to the fumarate) of the parent compound of the instant claims.
More specifically copending ‘’416 is directed to a unit dosage pharmaceutical composition comprising a small genus of compounds that that encompasses the parent compound of the instant claims. Claim 2 has 6 species, the 2nd of which is the instant parent compound.
The copending applications and patent each differ from the instant claims in that they are directed to the parent AKT inhibitor compound and not a crystalline form A of the fumarate hydrate of the compound.
The teachings of Sekhon BS are set forth above and incorporated herein.
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have formulated the specific AKT inhibitor of the copending claims (the instant parent compound) as the fumarate hydrate with a reasonable expectation of success. One would have been motivated to do so as fumarate co-crystals are a known technique for optimizing drug properties of pharmaceutical materials. Further the act of solvent drop grinding and co-sublimation are well-known means of forming co-crystals. Regarding the specific crystal form A of the fumarate hydrate, it does not appear that the fumarate hydrate forms any other forms so because it would have been obvious to formulate the fumarate hydrate co-crystal it only follows that it would form as crystal form A. Evidence supporting this position can be found in the instant specification which shows that different crystallization techniques (co-sublimation and seeding) both yield crystal form A. There is no evidence suggesting that any other forms are possible for the fumarate hydrate.
This is a provisional nonstatutory double patenting rejection with respect to the copending applications because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant argues they disagree with the examiner’s assessment but fail to provide any arguments. Accordingly, the rejections are maintained for reasons of record.
Conclusion
Claims 1-11, 13-14, 18-19 and 21-26 are rejected. 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. 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 Kortney Klinkel, whose telephone number is (571)270-5239. The examiner can normally be reached on Monday-Friday 10 am to 7 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Michener can be reached on 571-272-1424. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kortney Klinkel whose telephone number is (571)270-5239. The examiner can normally be reached on Monday-Friday 10 am to 7 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Michener can be reached on 571-272-14241424. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Kortney L. Klinkel/
Primary Examiner, Art Unit 1699
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