SOLID FORMS OF A 4H-PYRAN-4-ONE STRUCTURED CYP11A1 INHIBITOR

§103 §112 §DP

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 . Priority This application filed on 08/30/2023 is a U.S. National Stage filing under 35 U.S.C. Q 371 of International Application No. PCT/FI2022/050129, filed 02/28/2022, which claims the benefit of Finnish Application No. 20215215, filed 03/1/2021. Information Disclosure Statement The information disclosure statement (IDS) filed on 06/10/2024, 12/04/2025 and 07/30/2026, 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, except where noted. Status of claims Applicant’s amendments and arguments filed on 07/30/2026 have been received and have been carefully considered. Claim 11 was amended, claims 1-10, 14-17 and 21-32 were cancelled, and claims 36-37 were added. Claims 11-13, 18-20 and 33-37 are pending. Election/Restriction Applicant’s response filed on 03/18/2026 to Restriction/Election Requirement filed on 12/18/2025, is acknowledged. Applicant elected without traverse Group I drawn to crystalline forms of 2-(isoindolin-2- ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one. Claims 11-13 and 33 read on the elected Group. Claims 18-20 and 34-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Pursuant to the Election of Species Requirement, Applicant respectively elected without traverse, crystalline form 5 of 2-(isoindolin-2- ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable. Claims 11-13 and 33 read on the elected species. Thus, claims 11-13, 18-20, and 33-37 are pending with claims 18-20 and 34-35 are withdrawn from further consideration, and claims 11-13, 33, and 36-37 are under consideration. Withdrawn Abstract Objection Objection to the Abstract for improper language is withdrawn in view of applicant’s amendment filed on 07/30/2026. Withdrawn Claim Rejections - 35 U.S.C. 112(b) Rejection to claims 11-13 and 33 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for not defining the crystalline form 5, is withdrawn in view of Applicant amendment filed on 07/30/2026 that amended claim 11 by including the water content. Per instant specification, the small amounts of water between 0.3-0.6 do not result in different crystalline forms, nevertheless, same crystalline form 5 with small shift in the peak positions, see Figure 5, 6, and 7.1 Rejection Maintained 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. 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. § 103 Rejection over Belle in view of Barth and Morissette Claims 11-13 and 33 are rejected under 35 U.S.C. 103 as being obvious over D. Belle, et al. (US PG Pub 2019/0359601 A1, 11/28/2019 “Belle” cited in the IDS dated 06/10/2024) in view of Oksala, R., et al. "ODM-208, a novel CYP11A1-inhibitor as a therapeutic approach for the treatment of castration-resistant prostate cancer." Annals of Oncology 28 (2017): v8, “Oksala” cited in the PTO-892 dated 04/30/2026), W. Barth et al. (US Patent No. 4,432,987A, 02/21/1984, “Barth”, cited in the PTO-892 dated 04/30/2026) and S. Morissette, et al. Advanced Drug Delivery Reviews, Volume 56, Issue 3, 2004, Pages 275-300, “Morissette” cited in the PTO-892 dated 04/30/2026). This application currently names joint inventors and assignee. 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. Belle teaches CYP11A1 inhibitors of formula (I) for use as medicaments in the treatment of steroid hormone dependent conditions and diseases where CYP11A1 inhibition is desired, wherein the diseases include breast cancer and prostate cancer [0007]. Belle teaches compound 185 as species of formula (I) (the claimed compound), [page 96, comp. 185]: PNG media_image1.png 294 486 media_image1.png Greyscale Belle discloses that the compound is purified by crystallization. [page [1020], [1034], [1046]]. Belle discloses the preparation of compound 185 (the claimed compound), wherein the compound isolated as a solid. [page 56, [1015]]. However, Belle does not specifically recite the crystalline form 5 of compound 185 or the spectroscopic characterization. Also, one of ordinary skill in the art needs to select compound 185 from Belle’s list of CYP11A1 inhibitors. Oksala teaches that ODM-208 is a novel, oral, non-steroidal and selective inhibitor of CYP11A1 enzyme and suppresses the synthesis of all steroid hormones and precursors. ODM-208 2 is the same compound as Belle’s compound 185 and the claimed compound. Oksala teaches that ODM-208 inhibited adrenal and testicular hormone production. Oksala teaches ODM-208 inhibited tumor growth in the androgen dependent VCaP cells. Oksala teaches ODM-208 potently inhibits CYP11A1 enzyme and formation of pregnenolone and testosterone with low nM concentrations in vitro. Oksala teaches that in prostate cancer model, ODM-208 significantly inhibited tumor growth. In the same art area of pharmaceutical preparations and their use in treating disease, Barth teaches the following: “[c]rystalline forms of compounds are ordinarily preferable to the non-crystalline forms thereof. The crystalline materials have superior stability, appearance and handling characteristics when compared to their amorphous counterparts. For pharmaceutical use crystalline compounds are especially advantageous in manufacturing procedures and in formation and use of acceptable dosage forms such as solutions, suspensions, elixirs, tablets, capsules and various pharmaceutically elegant preparations required by the medical and pharmaceutical professions.” [Pg. 2, col. 1, ln. 60- col. 2, ln. 2]. Morissette teaches an automated high-throughput crystallization to form polymorphs, salts, co-crystals and solvate forms of pharmaceuticals [Title, abstract]. The prior art describes the successful application of the automated high-throughput technique to several known pharmaceuticals and details how thousands of crystallization conditions can be performed in parallel, computer analyzed and then used to produce the polymorphic forms of a given pharmaceutical [Page 296, para. 2]. At the time of invention, one of ordinary skill in the art would have been motivated to specifically pick compound 185 from Belle’s CYP11A1 inhibitors of formula (I) for preparing crystalline forms. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Belle teaches that the CYP11A1 inhibitors of formula (I) directed to the treatment of a disease related to CYP11A1 inhibition, particularly, prostate cancer, and Oksala teaches that compound ODM-208 (Belle’s compound 185) is a potent and selective inhibitor of CYP11A1 enzyme for treating prostate cancer and inhibiting adrenal and testicular hormone production. Oksala also teaches the potency of ODM-208 in inhibiting tumor growth in the androgen dependent VCaP cells and in prostate cancer model with low nM concentrations. One of ordinary skill in the art would have been motivated to prepare crystalline form 5 of the Belle potent CYP11A1 inhibitor, compound 185 because Barth teaches that crystalline forms are preferred over non-crystalline forms; have superior stability; are preferred in formulation of dosage forms; and are advantageous in manufacturing procedures. [page 2, col. 1, ln. 60- col. 2, ln. 2]. One of ordinary skill in the art practicing the Belle’s pharmaceutical compound 185 would form a crystalline form in accordance with the specific teaching of Belle. Utilizing the routine “High-throughput salt selection” taught by Morissette [page 285-287] one of ordinary skill in the art would arrive at the claimed invention. Specifically, because Belle teaches that compound 185 form solid and purified by crystallization. Thus, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the claimed invention. In the instant case, one of ordinary skill in the art would have a reasonable expectation of success in following the teaching of Belle and utilizing the well-known and routine automated high-throughput screening described by Morissette arrive at the claimed invention because such acts are conventional and routine in the art. One of ordinary skill in the art would be expected to apply methods within their technical grasp (such as automated high-throughput screening) to improve that which is already known in the art. The Supreme Court stated in KSR “if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person's skill.” KSR Intern. Co. v. Teleflex Inc., 127 S.Ct. 1727, 1731 (2007). Here, the use of an automated system to screen a pharmaceutical salt for crystallization is well known and specifically taught by Morissette. Therefore, the method is within the technical grasp of those of ordinary skill in the art and it would be obvious to one of ordinary skill in the art to use the same method and apply it to Belle’s compound. Regarding the spectroscopic characterization of the obvious product, such properties are inherent in the product (MPEP 2112.02: "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.). In this case, one of ordinary skill in the art would have reasonably considered producing the crystalline salt form 5 which would inherently show the same spectroscopic parameters as are in the claim. "[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on ‘inherency’ under 35 U.S.C. 102, or ‘prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same." In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977). Thus, claims 11-13 and 36-37 are rejected as prima facie obvious. Regarding claim 33, Belle teaches a pharmaceutical composition comprising a compound of formula (I) together with a pharmaceutically acceptable carrier [0089], wherein the composition formulated in dosage forms e.g., tablets, granules or capsules. [0718]. Response to Arguments Applicant argues: Belle does not provide any suggestion that the specifically claimed crystalline form of Compound I would exist. Belle does not provide a reasonable expectation that the claimed crystalline form would have the physical properties recited in the instant claims. Furthermore, Belle does not disclose a method to prepare the claimed crystalline form. Oksala does not describe the chemical structure of ODM-208. Oksala says nothing about Compound I or any of its crystalline forms. Barth does not cure the deficiencies of Belle because Barth does not say anything about Compound I. Morissette does not cure the deficiencies of Belle, Oksala, or Barth. Applicant refers to Braga and Grepioni to support the assertion that polymorph production is unpredictable. Price poses the question: "Can we predict the polymorphs of an organic molecule by computer modelling?" followed by the answer "[c]ertainly not today, at least at the level that would be desirable for the pharmaceutical industry" (p. 302, 1st two sentences of "Introduction"). Finally, Bernstein states that a great deal still needs to be learned and done before one can state with any degree of confidence the ability to predict a crystal structure, much less crystalline forms (p. 14, "Abstract"). Even assuming that it is somehow known that a compound exists in a solid form, it is generally unpredictable whether the compound will form more than one solid form. As described by Sheth et al, in KONA, No. 23 (2005), 36-48, a thorough understanding of the relationship between the physical structure and the properties of pharmaceutical solids is important in selecting the suitable form of an active pharmaceutical ingredient for development into a drug product. Examples 6a, 6b and 6d that describe form 5 as having prismatic, bulky crystals that have good processability and filterability. As described in Example 7, after ageing, the slurry samples consisted of crystalline form 5 (water content 0.3) of Compound I. As further described in Example 7, form 5 is stable in conditions with lower water activity. As known to PHOSITA, such conditions are often used in pharmaceutical processing. Applicant respectfully submits that while Belle discloses Compound I, it does not teach or suggest crystalline forms of Compound I or the specific crystallization conditions leading to claimed form 5. Examiner response: Applicant's arguments have been fully considered but they are not persuasive. First, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Compound 185 (ODM-208) taught by Belle and Oksala as potent and selective inhibitor of CYP11A1 enzyme for treating prostate cancer and inhibiting adrenal and testicular hormone production with low nM concentrations. Belle teaches that compound 185 is isolated as a solid and the compounds are purified by recrystallization. Thus, the effectiveness of the compound 185 as an active pharmaceutical agent for treating prostate cancer is taught by Belle and Oksala would motivate skilled artisan to prepare crystalline form of the compound, specifically because Belle teaches that the compound was isolated as a solid and purified by recrystallization. Motivation to prepare crystalline forms of compound 185 is also provided by Barth: crystalline forms are preferred over non-crystalline forms; have superior stability; are preferred in formulation of dosage forms; and are advantageous in manufacturing procedures. Utilizing the routine “High-throughput salt selection” taught by Morissette [page 285-287] one of ordinary skill in the art would arrive at the claimed invention. One of ordinary skill in the art would have a reasonable expectation of success in following the teaching of Belle and utilizing the well-known and routine automated high-throughput screening described by Morissette arrive at the claimed invention because such acts are conventional and routine in the art. One of ordinary skill in the art would be expected to apply methods within their technical grasp (such as automated high-throughput screening) to improve that which is already known in the art. Regarding the spectroscopic characterization, and the properties described by Applicant Example 6a, 6b and 6d and Example 7 including prismatic, bulky crystals that have good processability and filterability, of the obvious product, such properties are inherent in the product (MPEP 2112.02: "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.). In this case, one of ordinary skill in the art would have reasonably considered producing the crystalline salt form 5 which would inherently show the same spectroscopic parameters as are in the claim. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977). Regarding applicant’s asserted unpredictability, the evidentiary references provided by Applicant are acknowledged. However, these references do not provide the state of the art at the time of the invention because the references reflected the state of the art more than 20 years ago. The references do not provide support for unpredictability of compound 185 (ODM-208). There is no teaching by Belle, Oksala or the provided evidentiary reference, or the instant specification that preparing crystalline form of compound 185 is unpredictable or required undue experimentation. The generic teaching of these references does not consider factual evidence for the unpredictability of instantly claimed form 5. It appears that applicant question the chemical structure of ODM-208, however, the previous office action, page 8 footnote, refer to PubChem page for the chemical structure of ODM-208: Opevesostat | C21H26N2O5S | CID 135151902 - PubChem. 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. Non-Statutory Double Patenting over US Patent No. 10,717,726 B2 Claims 11-13, 33, and 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 21, 22, 23, 24, 27 and 35 of US Patent No. 10,717,726 B2 (US PG-PUB 2019/0359601 A1) in view of Oksala, R., et al. Annals of Oncology 28 (2017): v8, “Oksala” cited in the PTO-892 dated 04/30/2026), W. Barth et al. (US Patent No. 4,432,987A, 02/21/1984, “Barth”, cited in the PTO-892 dated 04/30/2026) and S. Morissette, et al. Advanced Drug Delivery Reviews, Volume 56, Issue 3, 2004, Pages 275-300, “Morissette” cited in the PTO-892 dated 04/30/2026). Although the claims at issue are not identical, they are not patentably distinct from each other because: Instant claims 11-13, 33, and 36-37 recites “a compound which is crystalline form 5 of 2-(isoindolin-2- ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) having an X-ray powder diffraction pattern comprising peaks, expressed in degrees 2-theta (± 0.2), at 9.4, 10.0, 10.5, 11.6, 13.5, 15.2, 16.5 and 20.0”, wherein the crystalline form contains from about 0.3 to about 0.6 molecules of water per 1 molecule of compound (I), and pharmaceutical dosage form comprising the compound of claim 11. US Patent No. 10,717,726 B2 recites a compound of formula (I), and claim 27 recites the claimed compound as species of formula (I) (claim 27, 11th compound). Claim 35 recites pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. The pharmaceutical composition is described as dosage form, e.g., tablets, granules, capsules [col. 38, ln. 19-23]. US Patent No. 10,717,726 B2 does not specifically recite the crystalline form 5 of claim 27 compound or the spectroscopic characterization. Also, one of ordinary skill in the art need to select compound of claim 27 from US Patent No. 10,717,726 B2 list of CYP11A1 inhibitors. Oksala, Barth and Morissette teach as discussed above, pages 8-9. The obviousness rationale is similar to the rationale in the obviousness Rejection above, pages 9-10. Non-Statutory Double Patenting over US Patent No. 11,098,032 B2 Claims 11-13, 33 and 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2 and 10 of US Patent No. 11,098,032 B2 in view of Oksala, R., et al. Annals of Oncology 28 (2017): v8, “Oksala” cited in the PTO-892 dated 04/30/2026), W. Barth et al. (US Patent No. 4,432,987A, 02/21/1984, “Barth”, cited in the PTO-892 dated 04/30/2026) and S. Morissette, et al. Advanced Drug Delivery Reviews, Volume 56, Issue 3, 2004, Pages 275-300, “Morissette” cited in the PTO-892 dated 04/30/2026). Although the claims at issue are not identical, they are not patentably distinct from each other because: Instant claims 11-13, 33 and 36-37 recites “a compound which is crystalline form 5 of 2-(isoindolin-2- ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) having an X-ray powder diffraction pattern comprising peaks, expressed in degrees 2-theta (± 0.2), at 9.4, 10.0, 10.5, 11.6, 13.5, 15.2, 16.5 and 20.0”, wherein the crystalline form contains from about 0.3 to about 0.6 molecules of water per 1 molecule of compound (I), and pharmaceutical dosage form comprising the compound of claim 11. US Patent No. 11,098,032 B2recites a compound of formula (ID), and claim 2 recites the claimed compound as species of formula (ID) (claim 2, 3rd compound). Claim 10 recites pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. The pharmaceutical composition is described as dosage form, e.g., tablets, granules, capsules [col. 38, ln. 35-38]. US Patent No. 11,098,032 B2does not specifically recite the crystalline form 5 of claim 2 compound or the spectroscopic characterization. Also, one of ordinary skill in the art need to select compound of claim 2 from US Patent No. 11,098,032 B2list of CYP11A1 inhibitors. Oksala, Barth and Morissette teach as discussed above, pages 8-9. The obviousness rationale is similar to the rationale in the obviousness Rejection above, pages 9-10. Non-Statutory Double Patenting over US Patent No. 12,030,871 B2 Claims 11-13, 33, and 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 9 of US Patent No. 12,030,871 B2 in view of Oksala, R., et al. "ODM-208, a novel CYP11A1-inhibitor as a therapeutic approach for the treatment of castration-resistant prostate cancer." Annals of Oncology 28 (2017): v8, “Oksala” cited in the PTO-892 dated 04/30/2026), W. Barth et al. (US Patent No. 4,432,987A, 02/21/1984, “Barth”, cited in the PTO-892 dated 04/30/2026) and S. Morissette, et al. Advanced Drug Delivery Reviews, Volume 56, Issue 3, 2004, Pages 275-300, “Morissette” cited in the PTO-892 dated 04/30/2026). Although the claims at issue are not identical, they are not patentably distinct from each other because: Instant claims 11-13 and 33 recites “a compound which is crystalline form 5 of 2-(isoindolin-2- ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) having an X-ray powder diffraction pattern comprising peaks, expressed in degrees 2-theta (± 0.2), at 9.4, 10.0, 10.5, 11.6, 13.5, 15.2, 16.5 and 20.0”, wherein the crystalline form contains from about 0.3 to about 0.6 molecules of water per 1 molecule of compound (I), and pharmaceutical dosage form comprising the compound of claim 11. US Patent No. 12,030,871 B2 recites in claim 1 the claimed compound, 3rd compound. Claim 9 recites pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. The pharmaceutical composition is described as dosage form, e.g., tablets, granules, capsules [col. 39, ln. 3-6]. US Patent No. 12,030,871 B2 does not specifically recite the crystalline form 5 of claim 2 compound or the spectroscopic characterization. Also, one of ordinary skill in the art need to select compound of claim 1 from US Patent No. 12,030,871 B2list of CYP11A1 inhibitors. Oksala, Barth and Morissette teach as discussed above, pages 8-9. The obviousness rationale is similar to the rationale in the obviousness Rejection above, pages 9-10. Non-Statutory Double Patenting over copending Application No. 18/548,486 Claims 11-13, 33, and 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of copending Application No 18/548,486 (US PG Pub 20240174654A1) in view of W. Barth et al. (US Patent No. 4,432,987A, 02/21/1984, “Barth”, cited in the PTO-892 dated 04/30/2026) and S. Morissette, et al. Advanced Drug Delivery Reviews, Volume 56, Issue 3, 2004, Pages 275-300, “Morissette” cited in the PTO-892 dated 04/30/2026). Although the claims at issue are not identical, they are not patentably distinct from each other because: Instant claims 11-13, 33 and 36-37 recites “a compound which is crystalline form 5 of 2-(isoindolin-2- ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) having an X-ray powder diffraction pattern comprising peaks, expressed in degrees 2-theta (± 0.2), at 9.4, 10.0, 10.5, 11.6, 13.5, 15.2, 16.5 and 20.0”, wherein the crystalline form contains from about 0.3 to about 0.6 molecules of water per 1 molecule of compound (I), and pharmaceutical dosage form comprising the compound of claim 11. copending Application No 18/548,486 recites in the claims a process of preparation of compound of formula (IA), the claimed compound. copending Application No 18/548,486 does not specifically recite the crystalline form 5 of claim 1 compound or the spectroscopic characterization. Barth and Morissette teach as discussed above, pages 8-9. The obviousness rationale is similar to the rationale in the obviousness Rejection above, pages 9-10. With regard to claim 33, one of ordinary skill in the art would have been motivated to prepare the crystalline form taught by copending Application No 18/548,486, Barth and Morissette because copending Application No 18/548,486 recites that the compound of claim 1 is a pharmaceutical compound useful for the treatment of breast and prostate cancer [page 1, ln. 20-21], and Barth teaches that pharmaceutical use crystalline compounds are especially advantageous in manufacturing procedures and in formation and use of acceptable dosage forms such as tablets, capsules and various pharmaceutically elegant preparations required by the medical and pharmaceutical professions.” [Pg. 2, col. 1, ln. 60- col. 2, ln. 2]. Non-Statutory Double Patenting over copending Application No. 18/548,487 Claims 11-13, 33, and 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2 and 21-24 of copending Application No. 18/548,487 (US PG Pub 20240158377A1) in view of Oksala, R., et al. Annals of Oncology 28 (2017): v8, “Oksala” cited in the PTO-892 dated 04/30/2026), W. Barth et al. (US Patent No. 4,432,987A, 02/21/1984, “Barth”, cited in the PTO-892 dated 04/30/2026) and S. Morissette, et al. Advanced Drug Delivery Reviews, Volume 56, Issue 3, 2004, Pages 275-300, “Morissette” cited in the PTO-892 dated 04/30/2026). Although the claims at issue are not identical, they are not patentably distinct from each other because: Instant claims 11-13, 33, and 36-37 recites “a compound which is crystalline form 5 of 2-(isoindolin-2- ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) having an X-ray powder diffraction pattern comprising peaks, expressed in degrees 2-theta (± 0.2), at 9.4, 10.0, 10.5, 11.6, 13.5, 15.2, 16.5 and 20.0”, wherein the crystalline form contains from about 0.3 to about 0.6 molecules of water per 1 molecule of compound (I), and pharmaceutical dosage form comprising the compound of claim 11. Copending Application No. 18/548,487 recites in claim 2 a salt of 2-(isoindolin-2- ylmethyl)-5-((1-(methyl sulfonyl) piperidin-4-yl) methoxy)-4H-pyran-4-one. Claim 21-24 recites pharmaceutical composition comprising a compound according to claim 1 and one or more excipients, wherein the composition is a dosage form including tablet or capsule. Copending Application No. 18/548,487 recites the salt of the claimed compound and does not specifically recite the crystalline form 5 of the compound or the spectroscopic characterization. Oksala, Barth and Morissette teach as discussed above, pages 9-10. Preparing the non-salt of copending Application No. 18/548,487 compound is obvious for the following reasons: Consistent with Sun Pharmaceutical Industries v. Eli Lilly and Col, 611 F. 3d 1381, 1387 (CAFC 2010), it is permissible to use a compound claim to reject a method of use claim where that method of use is disclosed in the specification of the application claiming the compound. According to the Sun Pharma. Court, “[i]t would shock one' s sense of justice if an inventor could receive a patent upon a composition of matter, setting out at length in the specification the useful purposes of such composition, . . .and then prevent the public from making any beneficial use of such product by securing patents upon each of the uses to which it may be adapted. . .”. In the instant case, copending Application No. 18/548,487 recites in the instant specification that the compound of claim 1 is a pharmaceutical compound useful for the treatment of breast and prostate cancer [page 1, ln. 17-18]. Oksala teaches that compound ODM-208 (not the salt) is a potent and selective inhibitor of CYP11A1 enzyme for treating prostate cancer and inhibiting adrenal and testicular hormone production. Oksala also teaches the potency of ODM-208 in inhibiting tumor growth in the androgen dependent VCaP cells and in prostate cancer model with low nM concentrations. Thus, one of ordinary skill in the art would have been motivated to prepare the non-salt of copending Application No. 18/548,487 compound for treating prostate cancer. The obviousness rationale for preparing the crystalline form 5 of the non-salt of copending Application No. 18/548,487 compound is similar to the rationale in the obviousness Rejection above, pages 9-10. Response to Arguments Applicant’s arguments are parallel to the arguments against the obviousness rejection above. Please refer to the Examiner response above. Conclusion Claims 11-13, 33 and 36-37 are rejected. No claim is 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 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 MANAHIL MIRGHANI ALI ABDALHAMEED whose telephone number is (571)272-1242. The examiner can normally be reached M-F 7:30 am - 5:00 pm. 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, James H Alstrum-Acevedo can be reached at 571-272-5548. 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. /M.M.A./Examiner, Art Unit 1622 /JAMES H ALSTRUM-ACEVEDO/ Supervisory Patent Examiner, Art Unit 1622 1 crystalline form 5 is in the form of a variable hydrate. The term "variable hydrate", as used herein, refers to a crystalline form that can incorporate various numbers of water molecules without disrupting the crystalline lattice. Thus, such crystalline form can incorporate either stoichiometric or non- stoichiometric amounts of water molecules within its lattice structure. Generally, the crystalline form 5 of compound (I) may contain up to about 1 molecule of water per 1 molecule of compound (I). In particular, the crystalline form 5 of compound (I) contains from about 0.3 to about 0.6, molecules of water per 1 molecule of compound (I). The X-ray powder diffraction pattern of crystalline form 5 having water content between about 0.3-0.6, about 0.3 and about 0.6 molecules of water per 1 molecule of compound (I) is demonstrated in Figures 5, 6 and 7, respectively. Accordingly, in one aspect, the crystalline form 5 is further characterized by a X-ray powder diffraction pattern as depicted in any one of Figures 5, 6 and 7. The small variations in the peak positions between Figures 5, 6 and 7 are related to the variable, non-stoichiometric water content embedded in the crystal structure of the variable hydrate crystalline form 5. 2 Compound ODM-208 structure is provided by PubChem: Opevesostat | C21H26N2O5S | CID 135151902 - PubChem