Detailed Action
The present office action is in response to the amendments filed on 12 Nov 2025.
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
Claims 1-7 of the pending application have been examined on the merits. Claims 8-18 are withdrawn (see “Response to Applicant Election” below).
Priority
Applicants identify the instant application, Serial #: 18/010,913, filed 16 Dec 2022, as a National Stage Entry of International Patent Application #: PCT/US2021/038051, filed 18 Jun 2021, which claims priority from U.S. Provisional Application #: 63/041,452, filed 19 Jun 2020.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 16 Dec 2022 and 12 Nov 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Applicant Election
Applicant’s election without traverse of Group I, claims 1-7, in the reply filed on 12 Nov 2025 is acknowledged.
Claims 8-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group I, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12 Nov 2025.
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.
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) 1-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/044844, hereinafter ‘844, further in view of Elder et al. (J Pharm Sci, 2010, 99:2948-2961), hereinafter Elder, and Haque et al. (Pharm Chem J, 2017, 50:837-850), hereinafter Haque.
The instant claims are drawn to a composition containing a methanesulfonic acid salt of Compound 1 (below) where at least 97% of Compound 1 is the mesylate salt (claim 1) and further include limitations that include a pharmaceutically excipient in the composition (claim 4).
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The claims limit the purity of Compound 1 to 98% and 99% mesylate salt (claims 2-3 and 5-6) and also limit the amount of solvent in the composition (claim 7).
‘844 teaches Compound 6 which has the same structure as instant Compound 1 (paragraph [0044]; Figure 1A; Claim 13):
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‘844 teaches Compound 6 inhibits both the ERG protein with an IC50 of 0.2727 µM and metastatic prostate cancer cell growth with an IC50 of 0.0739 µM (paragraphs [00155]-[00158]; Figs. 20 and 23). ‘844 also teaches a method of treating a disease by administering Compound 6 or a pharmaceutically acceptable salt of Compound 6 (claims 1, 9, and 13). ‘844 teaches that pharmaceutically acceptable salts include mesylate (paragraph [0098]). ‘844 teaches mixing the compounds of the reference with excipients to create a pharmaceutically acceptable aqueous suspension (paragraph [00142]). However, ‘844 does not teach a composition made up of Compound 1 where at least 97% of Compound 1 is a mesylate salt.
Elder teaches that about half of all active pharmaceutical substances (APIs) ultimately progressed as pharmaceutically acceptable salts and that salt formation is an integral part of the development process (pg. 2949, column 2). Elder teaches that salt formation with pharmaceutically acceptable counter-ions is an extremely useful approach for the optimization or modification of the physicochemical, processing, biopharmaceutical, or therapeutic properties of ionizable drug substances (pg. 2949, column 2). Elder further teaches that pharmaceutical salts can form hydrates during secondary processing which can be a problem, but that mesylates appear to have a much lower propensity to form hydrates which makes them an attractive salt form for secondary processing (pg. 2952, column 1). Elder teaches that the melting point of an API can be increased when making a sulfonic acid salt which increases stability of the API and leads to other processing advantages (pg. 2954, column 2). Elder concludes by teaching that sulfonate salts should not be discounted during the initial salt assessment simply due to perceived issues of safety and can be a vital appointment component of a balanced and thorough salt and form optimization process.
Haque teaches that the presence of impurities in APIs can have a significant impact on the quality and safety of drug products (pg. 838, column 2). Haque further teaches that the threshold for reporting impurities depending on the maximum dose, where a maximum dosage of ≤1 g/day requires reporting when impurities are at or above 0.1% and a maximum dosage of >1 g/day requires reporting when impurities are at or above 0.05% (pg. 839, Table 3). Haque further teaches that the solvents used in the synthesis of APIs are likely to contain a number of impurities.
Based on the teachings of ‘844, Elder, and Haque, a person of skill in the art would start with Compound 6, taught in ‘844, and test a finite number of pharmaceutically acceptable salts, such as those taught in ‘844, to optimize the physicochemical, processing, biopharmaceutical, or therapeutic properties of Compound 6, as taught by Elder. The artisan would further be motivated to include sulfonate salts in the salt screening, and more specifically include methanesulfonic acid (mesylate), because mesylates have superior qualities over other salts such as reduced hydrate formation, greater stability, and processing advantages, as taught by Elder.
The artisan would further be motivated to keep impurities of the mesylate salt formed from Compound 6 below the thresholds of 0.1% to reduce the reporting of impurities to the required agencies, making a compound that is a 99.9% mesylate salt of Compound 6, as taught by Haque. The artisan would recognize that solvents are potential sources of impurities and so ensure the mesylate salt of Compound 6 was substantially free of solvent, as taught by Haque.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. 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 was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 1-7 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1 and 7 of U.S. Patent No. 11,648,239, hereinafter ‘239.
‘239 teaches a pharmaceutical composition of the instant compound, or a pharmaceutically acceptable salt thereof, and an excipient. However, ‘239 does not teach a composition of the instant compound where at least 97% of the instant compound is a mesylate salt.
Elder teaches that about half of all active pharmaceutical substances (APIs) ultimately progressed as pharmaceutically acceptable salts and that salt formation is an integral part of the development process (pg. 2949, column 2). Elder teaches that salt formation with pharmaceutically acceptable counter-ions is an extremely useful approach for the optimization or modification of the physicochemical, processing, biopharmaceutical, or therapeutic properties of ionizable drug substances (pg. 2949, column 2). Elder further teaches that pharmaceutical salts can form hydrates during secondary processing which can be a problem, but that mesylates appear to have a much lower propensity to form hydrates which makes them an attractive salt form for secondary processing (pg. 2952, column 1). Elder teaches that the melting point of an API can be increased when making a sulfonic acid salt which increases stability of the API and leads to other processing advantages (pg. 2954, column 2). Elder concludes by teaching that sulfonate salts should not be discounted during the initial salt assessment simply due to perceived issues of safety and can be a vital appointment component of a balanced and thorough salt and form optimization process.
Haque teaches that the presence of impurities in APIs can have a significant impact on the quality and safety of drug products (pg. 838, column 2). Haque further teaches that the threshold for reporting impurities depending on the maximum dose, where a maximum dosage of ≤1 g/day requires reporting when impurities are at or above 0.1% and a maximum dosage of >1 g/day requires reporting when impurities are at or above 0.05% (pg. 839, Table 3). Haque further teaches that the solvents used in the synthesis of APIs are likely to contain a number of impurities.
Based on the teachings of ‘239, Elder, and Haque, a person of skill in the art would start with the instant compound, taught in ‘239, and test a finite number of pharmaceutically acceptable salts, such as those taught in Elder, to optimize the physicochemical, processing, biopharmaceutical, or therapeutic properties of the instant compound, as taught by Elder. The artisan would further be motivated to include sulfonate salts in the salt screening, and more specifically include methanesulfonic acid (mesylate), because mesylates have superior qualities over other salts such as reduced hydrate formation, greater stability, and processing advantages, as taught by Elder.
The artisan would further be motivated to keep impurities of the mesylate salt formed from the instant compound below the thresholds of 0.1% to reduce the reporting of impurities to the required agencies. The artisan would recognize that solvents are potential sources of impurities and so ensure the mesylate salt of the instant compound was substantially free of solvent.
Claims 1-7 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over U.S. Patent No. 10,238,639, hereinafter ‘639.
‘639 claims a method of treating a disease by administering a pharmaceutical composition comprising the instantly claimed Compound 1, or a pharmaceutically acceptable salt thereof, and an excipient (ref claim 1, 10, and 17). By teaching a method of administering the instant compound, ‘639 inherently shows possession of the instant compound. However, ‘639 does not teach a composition of the instant compound where at least 97% of the instant compound is a mesylate salt.
Elder teaches that about half of all active pharmaceutical substances (APIs) ultimately progressed as pharmaceutically acceptable salts and that salt formation is an integral part of the development process (pg. 2949, column 2). Elder teaches that salt formation with pharmaceutically acceptable counter-ions is an extremely useful approach for the optimization or modification of the physicochemical, processing, biopharmaceutical, or therapeutic properties of ionizable drug substances (pg. 2949, column 2). Elder further teaches that pharmaceutical salts can form hydrates during secondary processing which can be a problem, but that mesylates appear to have a much lower propensity to form hydrates which makes them an attractive salt form for secondary processing (pg. 2952, column 1). Elder teaches that the melting point of an API can be increased when making a sulfonic acid salt which increases stability of the API and leads to other processing advantages (pg. 2954, column 2). Elder concludes by teaching that sulfonate salts should not be discounted during the initial salt assessment simply due to perceived issues of safety and can be a vital appointment component of a balanced and thorough salt and form optimization process.
Haque teaches that the presence of impurities in APIs can have a significant impact on the quality and safety of drug products (pg. 838, column 2). Haque further teaches that the threshold for reporting impurities depending on the maximum dose, where a maximum dosage of ≤1 g/day requires reporting when impurities are at or above 0.1% and a maximum dosage of >1 g/day requires reporting when impurities are at or above 0.05% (pg. 839, Table 3). Haque further teaches that the solvents used in the synthesis of APIs are likely to contain a number of impurities.
Based on the teachings of ‘639, Elder, and Haque, a person of skill in the art would start with the instant compound, taught in ‘639, and test a finite number of pharmaceutically acceptable salts, such as those taught in Elder, to optimize the physicochemical, processing, biopharmaceutical, or therapeutic properties of the instant compound, as taught by Elder. The artisan would further be motivated to include sulfonate salts in the salt screening, and more specifically include methanesulfonic acid (mesylate), because mesylates have superior qualities over other salts such as reduced hydrate formation, greater stability, and processing advantages, as taught by Elder.
The artisan would further be motivated to keep impurities of the mesylate salt formed from the instant compound below the thresholds of 0.1% to reduce the reporting of impurities to the required agencies. The artisan would recognize that solvents are potential sources of impurities and so ensure the mesylate salt of the instant compound was substantially free of solvent.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Berge et al. (J Pharm Sci, 1977, 66:1-19) is considered pertinent for teaching a finite list of pharmaceutically acceptable salts which includes mesylate. Mohamed et al. (J Urol, 2017, 197:e1171) is considered pertinent for teaches a derivative, ERGi-USU#6, of the compound ERGi-USU shows increased efficacy against the ERG protein. Xavier et al. (Cancer Res, 2018, 77:2797) is considered pertinent for teaching ERGi-USU-6 has improved efficacy in selectively inhibiting the growth of ERG positive cancer cells. Eldhose et al. (Cancer Res, 2020, 80:615), published after the EFD, is considered for pertinent for teaching salt forms of ERGi-USU-6 and that ERGi-USU-6 has the same structure as instant Compound 1.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625