NON-FINAL REJECTION
This application is a 35 U.S.C. 371 (national stage) application of PCT/CN2022/075428, filed Feb. 8, 2022, which claims benefit of foreign priority to Chinese applications 202110172372.2, filed Feb. 8, 2021, and 202111315868.7, filed Nov. 8, 2021.
Claims 1-4, 7-8, 12-14, 18, 24-25, 28-32, and 34, as amended, are pending.
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
Acknowledgment is made of applicant's claim to foreign priority under 35 U.S.C. 119(a)-(d).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on Nov. 16, 2023 and Aug. 14, 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Election/Restrictions
Applicant's election with traverse of Group I, drawn to compounds, and compound (I-3) as the compound species, having the structural formula,
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in the reply filed on Jan. 9, 2026 is acknowledged. The traversal is on the ground(s) that, as provided in 35 U.S.C. § 121, restriction to one of two or more claimed inventions is proper only if the inventions are "independent and distinct." MPEP § 803 further provides that, if search and examination of two or more inventions can be made without "serious burden," the Examiner must examine them on the merits, even if the claims are directed to distinct or independent inventions, which they are not, as defined in MPEP § 803 (Remarks, p. 16).
However, this is a national stage application under 35 U.S.C. § 371. Search burden is not a consideration in unity of invention practice under 35 U.S.C. § 371 and 37 C.F.R. 1.499. See also MPEP §§ 1850, 1893.03(d), and 1896.
Applicant further contends that the claims have unity of invention because they are not obvious over the cited references, Ramharter et al. in view of Gillis et al. (Remarks, pp. 16-18).
While the deficiencies of Gillis et al. are noted, it remains that the claims do not present a contribution over the prior art, as detailed infra.
The requirement is still deemed proper and is therefore made FINAL.
Claims 24, 25, 31, 32, and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions and/or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on Jan. 9, 2026.
Claims 1-4, 7, 8, 12-14, 18, and 28-30 are currently pending and under consideration.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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.
Claims 1-4, 7, 8, 12-14, 18, and 28-30 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Ramharter et al. (WO2019/122129, of record) in view of Colby et al. (ChemMedChem 12, 1481-1490 (2017)), cited on PTO-892) and Cregg et al. (US Pub. 2023/0096028, cited on PTO-892).
Ramharter et al. disclose compounds of formula (I) as SOS1 inhibitors (abstract), including, e.g., compound (I-38) (Table 20, p. 163), shown side-by-side with the elected compound for comparison:
Ramharter et al. compound (I-38)
Elected compound species (I-3)
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Compound (I-38) reads on formula (I) as recited by claims 1-4, 7, 8, 12-14, and 18, to the extent that:
R1 is a 3-membered cycloalkyl (cyclopropyl) substituted by R11, where R11 is C1-6-alkyl (ethyl) substituted by halogen (fluoro); R2 is hydrogen; R3, R4, and R5 are each C1-6-alkyl (methyl), and m is 1; and Ring A is a 6-membered aromatic ring (phenyl).
The compounds of Ramharter et al. are disclosed and claimed in pharmaceutical compositions comprising one or more pharmaceutically acceptable excipient(s), and at least one other pharmacologically active substance (claims 26-27), e.g., trametinib (p. 24; p. 200), as recited by claims 28-30.
Compound (I-38) of Ramharter et al. differs from the elected compound (I-3) in that R6 is CF3 rather than SF5; and the adjacent R5 is methyl rather than hydrogen.
However, CF3 (trifluoromethyl) and SF5 (pentafluorosulfanyl) were well-known in the art as bioisosteres.
For example, Colby et al. teach that the pentafluorosulfanyl (SF5) group is more chemically and thermally stable, more lipophilic, and more electronegative than a trifluoro-methyl (CF3) substituent (p. 1481, right col. to p. 1482, left col.), such that SF5-containing ligands have shown equivalent or higher activity than CF3-based ligands (p. 1485, left col.). Numerous published examples show that introducing an SF5 group into a compound could increase its selectivity, and improve the electrostatic interactions of the ligand with the binding site, which may result in improved selectivity as well as potency (p. 1488, left col.).
Thus, Colby et al. teach the SF5 group as a bioisosteric replacement of the CF3, tert-butyl, halogen, and NO2 groups as substituents on an aromatic ring; describe many cases where SF5-containing ligands displays higher activities than their CF3 analogues; and conclude that the SF5 group has repeatedly proven its utility as an analogue of the CF3 group. (p. 1489, right col.).
Further, Cregg et al. disclose and claim compounds which are SOS1 inhibitors, methods of treating diseases associated with SOS1, and methods of synthesizing these compounds (abstract; claims 24-30).
In particular, Cregg et al. exemplify the compounds of Example 462 (paras. [0866]-[0869]) and Example 477 (paras. [0924]-[0925]), shown side-by-side for comparison:
Cregg et al. Example 477
Cregg et al. Example 462
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Compounds 462 and 477 are structurally similar SOS1 inhibitors bearing either a SF5 (penta-fluorosulfanyl) or a CF3 (trifluoromethyl) substituent, respectively. While the structural core of the compounds of Cregg et al. differs slightly from those claimed, Colby et al. and Cregg et al. demonstrate that CF3 and SF5 were known as bioisosteric replacements in the context of small molecule SOS1 inhibitors.
Regarding the methyl group at R5 in compound 38 of Ramharter et al., the compounds of Cregg et al. suggest the replacement of the methyl group at R5 and the CF3 group at R6 with hydrogen at R5 and SF5 at R6, with no loss of function as SOS1 inhibitors.
Further, hydrogen and methyl substitutions are known in the art and have been held to be obvious variants of each other. See In re Wood, 582 F.2d 638, 199 USPQ 137 (CCPA, 1978). The interchange of an alkyl group and hydrogen, in and of itself, is obvious. See Ex Parte Bluestone, 135 USPQ 199 (B.P.A.I. 1961); In re Lincoln and Byrkit, 53 USPQ 40 (C.C.P.A. 1942); In re Druey and Schmidt, 138 USPQ 39 (C.C.P.A. 1963); In re Lohr and Spurlin, 137 USPQ 548 (C.C.P.A. 1963); In re Hoeksema, 158 USPQ 596 (C.C.P.A. 1968); In re Hoke, 195 USPQ 148 (C.C.P.A. 1977); Ex parte Fauque, 121 USPQ 425 (B.P.A.I. 1954); Ex parte Henkel, 130 USPQ 474, (B.P.A.I. 1960).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art as of the effective filing date to replace CF3 in the compounds of Ramharter et al. with SF5 as taught by Colby et al. and Cregg et al. to arrive at the elected compound with a reasonable expectation of success, because Colby et al. teach the SF5 group as a bioisosteric replacement for a CF3 substituent on an aromatic ring; and the compounds of Ramharter et al. and Cregg et al. are both disclosed to have the same utility and mechanism of action as the claimed compounds, as SOS1 inhibitors useful for the treatment of cancer.
As recognized by MPEP § 2144.09, a prima facie case of obviousness may be made
when chemical compounds have (1) very close structural similarities and (2) similar utilities.
"An obviousness rejection based on similarity in chemical structure and function entails the
motivation of one skilled in the art to make a claimed compound, in the expectation that
compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313,
203 USPQ 245, 254 (CCPA 1979).
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, 7, 8, 12-14, 18, and 28-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-14, and 18-24 of copending Application No. 19/101,315 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the examined claims would be anticipated by the reference claims.
Specifically, the reference claims are drawn to
crystal forms and salts of the elected compound species (I-3);
methods of making and using the elected compound species; and
compositions comprising the elected compound species, an additional active agent (e.g., trametinib), and a pharmaceutically acceptable carrier.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Citation of Additional Prior Art
Additional references made of record are considered pertinent to applicant's disclosure: USPN 10,898,487 (cited on PTO-892).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 9:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA ELIZABETH TOWNSLEY/Examiner, Art Unit 1629