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 .
The amendment filed 29 April 2026 has been received, entered and considered. The following information has been made of record in the instant amendment:
1. Claims 3, 8, 10, 12-13, 16, 20-21, 23-24, and 27-34 have been canceled.
2. New Claims 38-39 have been added.
3. Claims 1-2, 22, 25, and 36 have been amended.
4. Remarks drawn to rejections under 35 USC 112, 102, and 103.
The following objection(s)/rejection(s) has/have been overcome:
5. The rejection of Claims 22 and 36 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been overcome by amendments.
6. The rejection of Claim(s) 1, 4-5, 7, 9, 11, 14-15, 19 and 37 under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al (J. Med. Chem. 2019, 62, 10783-10797; Cited in IDS filed 02/07/2024), and the rejection of Claim(s) 1, 4-5, 7, 9, 11, 14, 19, and 37 under 35 U.S.C. 102(a)(1) as being anticipated by Babault et al (J. Med. Chem., 2018, 61, 1541-1551; cited in IDS filed 02/07/2024) has been withdrawn in view of the amendment to claim 1 which now requires L1 in formula (I) to be C3-C5 alkenyl. Both references teach compounds that have alkyl for L1 in instant formula (I).
Claims 1-2, 4-7, 9, 11, 14-15, 17-19, 22, 25-26, and 35-39 are pending in the case.
The following rejection is necessitated by Applicant's amendment filed 29 April 2026 wherein the limitations in pending claims 1-2, 22, 25, and 36 have been amended.
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) 1-2, 4-7, 9, 11, 14-15, 17-19, 22, 25-26, and 35-39 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (J. Med. Chem. 2019, 62, 10783-10797; Cited in IDS filed 02/07/2024; of record, and necessitated by amendment).
Chen et al teaches compounds 1a-d, 1a*, 1j, 2a-d, 3a-b (Schemes 1, 3, 4 and 5, Figure 5). The said compounds have part of the structural features of the compound formula I in claim 1, have electron withdrawing group as in claim 4, and read on the limitations of claims 5-7, 9, 11, 14, 19 (amide), and 25.
Chen teaches a method for the inhibition of NNMT in vitro comprising its compounds (page 10794, right col., first para; as in claim 37).
Chen does not expressly teach X = CH, L1 = C3-C5 alkenyl, the other substitutions for R, R1-R7, pharmaceutically acceptable salts, stereoisomers or prodrug thereof as in claim 1, and some of the limitations of claims 2, 5-6, 9, 11, 14-15, 19, 25-26, 35-39.
Chen teaches compound 2a* which has an alkynyl group for L1(Scheme 4). The precursor to this compound is compound 2, which is obtained from compound 9. One of ordinary skill in the art will recognize that by a judicious choice of protecting groups (same as masking groups) one can obtain compound 2a* with ester and amino group also protected. The precursor compound 9 has the CN substitution on the phenyl ring which can be carried over to the final product. The CN and the amide groups are electron withdrawing groups. These groups can be moved around in the phenyl ring at different positions as in formula I in claim 1. This also renders obvious the substitution of other electron withdrawing groups on the phenyl ring 1, 6, 17-19, 22 and 25, and R2 = H as in claim 14, as variants. Since Chen teaches a linker group having an alkynyl moiety, and an alkyl moiety, one of ordinary skill in the art would make the compound of formula I as in claim 1 with an alkenyl moiety also since it is between an alkyl and alkynyl moiety (limitation of claims 1, 2, 6 and 25-these have alkenyl moiety in the linker L1). The artisan can also use the substitutions for R as in claim 5-6, making groups C1-C6 alkyl and benzyl for R1as in claims 9 and 11 and the third and fourth substitution in claim 15 since these would serve as prodrugs of formula I (as in claim 1).
Since the compounds of Chen are inhibitors of NMMT and NMMT has been linked to various diseases, the artisan would make the pharmaceutical compositions of the compounds including stereoisomers, solvates and salts as in claim 26 and use them as active agents in the method of treatment of a condition which is modulated by the inhibition of NNMT and the diseases/conditions as in claims 35-39 since Chen teaches that NMMT is associated with all of the claimed conditions/diseases (see Chen-Introduction). It would be obvious to the artisan to make the compounds of formula (I) with the alkenyl moiety and all the other substitutions as recited in the instant claims in order to look for compounds with enhanced NMMT activity because Chen teaches NMMT activity for compounds that have both the alkyl and the alkynyl groups for L1 in instant formula (I) (page 10787, Fig. 5). The artisan would also substitute other electron-withdrawing groups for R3 as in claim 4 in view of Chen.
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.'" KSR, 550 U.S. at, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
According to the rationale discussed in KSR above, the rationale in (G) above is seen to be applicable here since based on the prior art teachings, compounds embraced by instant formula I are NMMT inhibitors and NMMT is implicated in many diseases and conditions. Inhibitors of NMMT would be useful as active agents in a method of treating diseases and conditions associated with NMMT. Thus, it is obvious to arrive at the claimed compounds of formula (I), make their pharmaceutical compositions and use them in the claimed methods in view of Chen et al. Compounds which differ only in the placement of substituents in a ring system are not patentable absent unexpected results. In re Jones 162 F. 2d 638, 74, USPQ 152 (CCPA 1947).
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the teachings of Chen et al.
One of ordinary skill in the art would be motivated to look for other similar compounds that act as potent NMMT inhibitors for testing and using in the claimed methods of treatment.
Response to Applicant’s Remarks
Applicant has traversed the rejection of the claims under 35 USC 103 over Chen arguing that the bond angles of the sp2-hybridized alkenyl group would be different from the sp-hybridized alkynyl group. The geometry of the resulting compounds will also be different, the alkenyl group being trigonal planar and the alkynyl group being linear.
Furthermore, the data in the present application as filed show that compounds of Chen, with alkyl or alkynyl linker and meta-amide substitutions, are less active than example compounds as set forth in the claims. See data in Table 1 for claimed compounds (comprising alkenyl group plus para electron withdrawing group), compared with Chen disclosed reference compounds GYZ-655 (Table 4) and GYZ-644 (Table 5). At least for these reasons provided the instant claims are non-obvious over Chen (page 3-Remarks).
Applicant’s arguments are not persuasive. Chen teaches compounds that have both the alkyl group and alkynyl group for the linker L1 in instant formula (I). Compounds having both these linkers and the electron withdrawing amide group at the meta position of the phenyl ring are inhibitors of NMMT. Therefore, the artisan would have a reasonable expectation that compounds having an alkenyl group as the linker and an electron withdrawing group in the para-position with respect to the attachment of the linker L1 would also show the same activity.
From Chen’s teaching regarding the activity of the compounds, and that have both the alkyl and the alkenyl groups for L1, the artisan will recognize that the alkyl group with sp3 hybridization and the alkynyl group which sp-hybridized and linear are both active (Chen-page 10787, Fig. 5). Therefore, irrespective of the hybridization and shape, the artisan would expect the alkenyl group with sp2-hybridization and trigonal planar will all also be active, and would therefore make the instant compounds of formula (I) in order to look for variants of the compounds of Chen that show enhanced NMMT activity and use them in the claimed methods of treatment. It is obvious to move the electron withdrawing group on the phenyl ring to the adjacent position, para- to the position of attachment of the linker. Compounds which differ only in the placement of substituents in a ring system are not patentable absent unexpected results. In re Jones 162 F. 2d 638, 74, USPQ 152 (CCPA 1947).
The artisan would have seen the results applicant has seen as disclosed in Table 1.
The instant claims are rendered obvious over the teachings of Chen. The rejection is maintained.
Conclusion
1. Pending claims 1-2, 4-7, 9, 11, 14-15, 17-19, 22, 25-26, and 35-39 are rejected.
2. Claims 3, 8, 10, 12-13, 16, 20-21, 23-24, and 27-34 have been canceled.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 GANAPATHY KRISHNAN whose telephone number is (571)272-0654. The examiner can normally be reached M-F 8.30am-5pm.
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/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693
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