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
The office acknowledges Applicants response filed on 7/20/2026 in regards to the restriction requirement dated 5/12/2026. Claims 1-5, 7-8, 10-11, 13-14, 16-18, 20, 22, 23, 25-28, 31-33 are pending. Applicants have elected group I, claims 1-5, 7, 8, 10-11, 13-14, 27, 28 and 31 without traverse. Further elected p-tolunesulfonic acid salt of 5-((1- (methylsulfonyl)piperidin-4-yl)methoxy)-2-((5-(trifluoromethyl)isoindolin-2-yl)methyl)-4H- pyran-4-one, and prostate cancer as a single hormonally regulated cancer without traverse. Claims 16-18, 20, 22-23, 25-26 and 32-33 are withdrawn from further consideration pursuant to 37 C.F.R. 1.142(b), as being drawn to non-elected subject matter. The restriction requirement is made final. For the sake of compact prosecution allowable subject matter was discussed with Applicants’ representative, Dr. Bhumralker on 8/3/2026. Applicants requested that an office action be mailed (8/5/2026). The claims corresponding to the elected subject matter are 1-5, 7, 8, 10-11, 13-14, 27, 28 and 31 and are herein acted on the merits.
Application Priority
This application filed 04/25/2024 is a National Stage entry of PCT/FI2022/ 050704, International Filing Date: 10/27/2022, claims foreign priority to 20217161, filed 10/28/2021.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 7/11/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the Examiner.
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.
Claim(s) 1-4, 10, 13, 27, 28 are rejected under 35 U.S.C. 103 as being unpatentable over Din Belle (IDS: WO 2018115591), Gupta et al. (Molecules 2018, 23, 1719, p 1-15) and Chen (Crytal Growth and Design, 2011, 887-895).
Din Belle disclose pyran derivatives as cyp11a1 (cytochrome p450 monooxygenase 11a1) inhibitors, and pharmaceutically acceptable salts (Abstract, p 9, line 1 and p ), in particular, 5 -((1 -(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl) isoindolin- 2-yl)methyl)-4H-pyran-4-one (Compound 184) (claim 27, p 40, lines 3-4). The compounds are useful as medicaments in the treatment of diseases and conditions, such as prostate cancer (Abstract). The reference teaches that the purification method includes crystallization (p 21, line 5). Optically active enantiomers or diastereomers of compounds of formula (I) can be prepared e.g. by resolution of the racemic end product by known methods (p 34, lines 27-31, p 35, lines 1-2). The reference explicitly teaches that pharmaceutically acceptable salts are well known in the field of pharmaceuticals. Non-limiting examples of salts with inorganic or organic acids include chlorides, bromides, phosphates, sulfonates, methane sulfonates, formates, tartrates, maleates, citrates, benzoates, salicylates, ascorbates, acetates, oxalates, fumarates, hemifumarates, and succinates (p 35, lines 7-15). The reference teaches the formulation of the compounds with excipients and in the dosage forms, e.g. tablet (p 57, lines 21-24).
Gupta et al. disclose that the specific salts of active pharmaceutical ingredients (APIs) are often formed to achieve desirable formulation properties. Although addressing poor aqueous solubility is one of the most important reasons to employ a salt formation, pharmaceutical companies also use the formation of unique salt
products to commonly address other physicochemical and biological concerns such as stability, toxicity, poor absorption, and issues related to manufacturing processes (See p 1, Introduction). Table 1 list the counterions for salt formation, e.g. chloride, bromide, phosphate, maleate, benzenesulfonate. Also taught briefly regarding screening, preparation and characterization of salts (p 12, para 1). It is taught that the salt formation of an API is an integral part of the formulation development process. The counterions of the salts that are used can positively affect the applicability of the drugs in various dosage forms by improving the formulation properties. The appropriate salt form of the API is important in order to achieve the desired outcome, and can also have an immense economic impact (p 12, last para).
Chen teaches crystallization of pharmaceuticals. Chen teach that pharmaceutical research involving an active pharmaceutical ingredient (API) often deals with various solid forms that include solids, salts, solvates co-crystals etc. (See p 889, col. 1, para 2). Salts make APIs more bioavailable (p 891, col. 2, line 21). The reference disclose that crystallization is an important separation and purification process to produce pharmaceuticals, the control of crystal size, shape and crystal form is crucial and they can influence the physical and chemical properties of the solid such as dissolution rate and solubility (p 887, Introduction). Further taught is that crystallization is important in the pharmaceutical industry as a separation process for intermediates and often serves as the final step in the manufacture of active pharmaceutical agents (API) (p 887, para 1, lines 7-10). The reference discusses the production of crystals in page 889.
From the teachings of Din Belle and Gupta a skilled artisan before the effective filing date of the invention would have found it obvious to arrive at the claimed salts of 5 -((1 -(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl) isoindolin- 2-yl)methyl)-4H-pyran-4-one. A person skilled in the art would have been motivated to arrive at the claimed salt(s) with a reasonable expectation of success and to improve the properties of the compound, for e.g. solubility and other physicochemical properties. Thus claims 1-2 are addressed. As to claims 3-4, 10, 13, Din Belle teaches purification of compounds using crystallization method and Chen teaches that crystallization is an important separation and purification process to produce pharmaceuticals. Hence a skilled artisan would have been motivated to arrive at the crystals of the salts of 5 -((1 -(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl) isoindolin- 2-yl)methyl)-4H-pyran-4-one. From the teachings of Din Belle a skilled artisan would have found it obvious to arrive at the pharmaceutical composition comprising 5 -((1 -(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl) isoindolin- 2-yl)methyl)-4H-pyran-4-one with excipients, and in the dosage form, for e.g. tablets with a reasonable expectation of success and use it for medical treatment, thus addressing claims 27-28.
Claim 31 is are rejected under 35 U.S.C. 103 as being unpatentable over Din Belle (IDS: WO 2018115591), Gupta et al. (Molecules 2018, 23, 1719, p 1-15) and Chen (Crytal Growth and Design, 2011, 887-895) in view of Gupta et al. (International Journal of Pharmaceutics, online July 9 2020, p 1-11, hereinafter Gupta2).
Din Belle, Gupta and Chen teachings as above. The rejection above is incorporated herein.
The prior art is not explicit in teaching the preparation of the tablets by wet granulation.
Gupta2 discloses the process of making low dose micro-tablets by high shear wet granulation process. The reference describes the technology and the process to prepare tablets (Abstract).
A person skilled in the art before the effective filing date of the invention would have found it obvious to prepare the tablet dosage form comprising the salt(s) of salts of 5 -((1 -(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl) isoindolin- 2-yl)methyl)-4H-pyran-4-one from Gupta2. A person skilled in the art would have been motivated to arrive at the tablets as in the instant claims with a reasonable amount of success and to use them as a dosage form in therapeutic treatment. Thus claim 31 would have been obvious over the combined prior art teachings.
Allowable Subject Matter
Claims 5, 7-8, 11, 14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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 1-4, 10, 13, 27, 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 27-28, 25 of U.S. Patent No. 10717726 (‘726) or claims 1, 2, 10 of US 11098032 (‘032) or claims 1, 13 of US 12030871 (‘871) in view of Din Belle (IDS: WO 2018115591), Gupta et al. (Molecules 2018, 23, 1719, p 1-15) and Chen (Crytal Growth and Design, 2011, 887-895).
The instant claims are directed to:
PNG
media_image1.png
330
725
media_image1.png
Greyscale
The dependent claims are limited to select salts and crystalline, pharmaceutical composition(s).
‘726 claims are directed to pyran derivatives as CYP11A1 inhibitors and its pharmaceutically acceptable salts, in particular, 5-((1-(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5-(trifluoromethyl)isoindolin-2-yl)methyl)-4H-pyran-4-one (see claims 27, 28). Also claimed is a pharmaceutical composition comprising a compound and a pharmaceutically acceptable carrier (claim 25).
‘032 reference claims are directed to pyran derivatives as CYP11A1 inhibitors and its pharmaceutically acceptable salts, in particular, 5-((1-(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5-(trifluoromethyl)isoindolin-2-yl)methyl)-4H-pyran-4-one (see claim 2). Also claimed is a pharmaceutical composition comprising a compound and a pharmaceutically acceptable carrier (claim 10).
‘831 reference claims directed to pyran derivatives as CYP11A1 inhibitors and its pharmaceutically acceptable salts, in particular 5-((1-(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5-(trifluoromethyl)iso-indolin-2-yl)methyl)-4H-pyran-4-one (see claim 1). Also claimed is a pharmaceutical composition comprising a compound and a pharmaceutically acceptable carrier (claim 13).
‘360 reference claims a process for the preparation of a compound of formula (lA) or a pharmaceutically acceptable salt thereof (see claims 34-36).
PNG
media_image2.png
129
280
media_image2.png
Greyscale
The reference claims are not explicit in teaching the specific salts as claimed.
Din Belle, Gupta et al. and Chen as discussed above.
From the teachings of Din Belle and Gupta a skilled artisan before the effective filing date of the invention would have found it obvious to arrive at the claimed salts of 5 -((1 -(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl) isoindolin- 2-yl)methyl)-4H-pyran-4-one. Thus claims 1-2 are addressed. As to claims 3-4, 10, 13, Din Belle teaches purification of compounds using crystallization method and Chen teaches that crystallization is an important separation and purification process to produce pharmaceuticals. From the teachings of Din Belle a skilled artisan would have found it obvious to arrive at the pharmaceutical composition comprising 5 -((1 -(Methylsulfonyl)piperidin-4-yl)methoxy)-2-((5 -(trifluoromethyl) isoindolin- 2-yl)methyl)-4H-pyran-4-one with excipients, and in the dosage form, for e.g. tablets with a reasonable expectation of success and use it for medical treatment, thus addressing claims 27-28.
Note: In regards to 18/573,360, this is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to UMAMAHESWARI RAMACHANDRAN whose telephone number is (571)272-9926. The examiner can normally be reached M-F- 8:30-5:00 PM (PST).
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, Kortney Klinkel can be reached at 5712705239. 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.
/Umamaheswari Ramachandran/Primary Examiner, Art Unit 1627
Prosecution Insights