Detailed Action
The present office action is in response to the amendments filed on 22 Jun 2026.
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 Claims 8-18 remain withdrawn.
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.
Response to Applicant Arguments
Acknowledgement is made of the remarks filed 22 Jun 2026.
Regarding the rejection of claims 1-7 under 35 U.S.C. § 103 over WO 2017/044844 (provided in the office action mailed 03 Mar 2026), hereinafter ‘844, further in view of Elder et al. (J Pharm Sci, 2010, 99:2948-2961; provided in the office action mailed 03 Mar 2026), hereinafter Elder, and Haque et al. (Pharm Chem J, 2017, 50:837-850; provided in the office action mailed 03 Mar 2026), hereinafter Haque, applicant arguments have been fully considered but are not persuasive.
Applicant argues on pgs. 6-7 of the remarks that Compound I (below) provides unexpected results of superior inhibition of ERG and RIOK2 protein levels in ERG positive prostate cancer cells according to data provided in Example 3 of the specification.
PNG
media_image1.png
102
166
media_image1.png
Greyscale
Table 2 (Specification, paragraph [0114]) shows that the mesylate salt of Compound I (listed as Compound 2 in Table 2) has a lower inhibition at 0.17 µM versus 0.23 µM for the free base of Compound I.
This is not persuasive. The lower inhibition of the mesylate salt is not significantly lower or higher as to be unexpected as variation in pharmacodynamic parameters would be expected in salt formation.
Applicant argues on pg. 7 of the remarks that the mesylate salt of Compound I exhibits unexpected results and has superior cytotoxicity against VCaP cells and inhibition of RIOK2 protein compared to other salts.
This is not persuasive. The lower inhibition of the mesylate salt is not significantly lower or higher as to be unexpected as variation in pharmacodynamic parameters would be expected in salt formation.
Applicant argues on pg. 7 of the remarks that the reference of Eldhose et al. (2021) supports the unexpected technical effect of methanesulfonic acid salt.
This Is not persuasive. No reference of Eldhose et al. (2021) has been provided in an IDS and so the reference has not been considered.
In light of the discussion above, the rejection of claims 1-7 under 35 U.S.C. § 103, as obvious over ‘844, Elder, and Haque is maintained for the reasons of record and restated below.
Regarding the obviousness-type nonstatutory double patenting rejections of claims 1-7 over U.S. Patent No. 11,648,239, Elder, and Haque, and claims 1-7 over U.S. Patent No. 10,238,639, Elder, and Haque, applicant arguments have been fully considered but are not persuasive.
Applicant argues on pg. 8 of the remarks that the unexpected results of the mesylate salt of Compound I (see above) is enough to overcome the double-patenting rejections over U.S. Patent No. 11,648,239 and U.S. Patent No. 10,238,639.
This is not persuasive for the reasons stated above. The rejection is maintained and restated below.
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).
PNG
media_image2.png
98
164
media_image2.png
Greyscale
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):
PNG
media_image3.png
201
138
media_image3.png
Greyscale
‘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.
Conclusion
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.
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.
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, Andrew Kosar can be reached at (571) 272-0913. 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.
/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
Prosecution Insights