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
This application is a 371 of PCT/CN2021/139172 (12/17/2021)
and claims foreign priority to CHINA 202011499721.3 (12/17/2020)
and CHINA 202111521781.5 (12/13/2021).
Status
Claims 7-14 are pending.
Claim rejections not reiterated are withdrawn.
Claim Rejections - 35 USC § 103
Claims 7-14 are rejected under 35 U.S.C. 103 as being unpatentable over Godbout et al. (WO 2020114947, publ. 2020-06-11) in view of Casimiro et al. (US20190315715, “Casimiro-2019”), Casimiro et al. (US20180148420, “Casimiro-2018”) and Wermuth (“The Practice of Medicinal Chemistry”, 4th ed. (2015), Ch. 8, pages 181-241).
Amended claim 7 is to several species including compound 35
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Godbout teaches a genus of vanin-1 inhibitors as pharmaceutical agents including Example 9.6 (p. 1-3; claims 11, 12):
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having an experimental vanin IC50 of 0.42 nM (Table 1).
Godbout Example 9.6 differs from the instant claim 7’s compound 35 by a pyridyl vs. pyrimidinyl ring, i.e., a C vs. N at the position annotated above.
Godbout also teaches compounds with sub-nanomolar vanin-1 IC50 -
Ex 1.11 (IC50 0.14 nM): Ex 9.3 (IC50 0.17 nM):
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,
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,
Ex 8.11(IC50 0.34 nM):
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.
Godbout teaches the compounds are useful for treating Crohn’s disease (claim 14).
Casimiro-2019 teaches vanin-1 inhibitor pharmaceutical compounds (Title, claim 34), including examples such as Example 1 and 149:
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experimentally demonstrated as vanin-1 inhibitors with IC50’s of 1.312 nM and 0.67 nM, respectively (Table 6). Casimiro-2019 teaches numerous structurally related compounds with high levels of vanin-1 activity in assays, as well as in human plasma (Table 6, [0751]).
Casimiro-2018 teaches vanin-1 inhibitor pharmaceutical compounds (Title, claim 8) including examples such as Examples 1, 17, and 73:
1
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73
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experimentally demonstrated as vanin-1 inhibitors with IC50’s of 4.1, 0.8, and 1.7 nM, respectively (Table 1). Casimiro-2018 teaches high levels of activity in numerous related compounds (Table 1, [0891]) and provided an in vivo demonstration of success (mouse model [0892]).
Together, Casimiros (Casimiro-2018 and Casimiro-2019) teach vanin-1 inhibitors as pharmaceutical agents with both the central pyrimidine ring motif have nM-level IC50 activity.
One of ordinary skill in the art following the teaching of Godbout would have considered modifying the pyridine ring to a pyrimidine ring based on Casimiro’s success with structurally related compounds having identical utility. In particular, Godbout’s and Casmiros’s experimental demonstration of nanomolar level activity would have provided an expectation that modifying the pyridine to the pyrimidine motif would result in compounds with similar levels of activity. Modifications of a pyridine to pyrimidine are routine bioisosteres known in the art and specifically taught by Wermuth (p. 193: pyrminidinyl bioisostere of pyridine, Fig. 8.11). One of ordinary skill in the art would have had a reasonable expectation of success because both Godbout and Casimiros are in the same field of endeavor and have the same target of vanin-1. Thus, claim 7 is prima facie obvious.
Regarding claim 8, Godbout teaches pharmaceutical formulation including with an excipient (claim 12). Regarding claims 9-14, Godbout teaches administering a therapeutically effective amount to a subject to treat vanin-related conditions including Crohn’s disease (p. 16-17, claim 14).
With each of the claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
Response to Remarks - 35 USC § 103
Applicant argues that Godbout in view of Casimiros and Wermuth does not contain any guidance as to how to obtain a new class of compounds with better vanin-1 inhibitory activity.
This argument is not persuasive because one of ordinary skill in the art would utilized the technique of bioisosterism, as is routine in the art and taught by Wermuth, in view of the teaching of successful inhibitors by Godbout and Casimiros and have an expectation that modifying the pyridine ring to a pyrimidyl ring as in Casimiros would result in compounds with similar utility.
Applicant argues that Godbout and Casimiros teach compounds that have inhibitory activity at levels such that one of ordinary skill in the art would not have considered or predicted pyrimidine compounds would be successful as a vanin-1 inhibitor.
This argument is not persuasive because as detailed above the cited art teaches structurally related compounds that showed nanomolar level IC50 activity with a pyridine and a pyrimidine. Thus, one of ordinary skill in the art would have had an expectation that the modification would be successful.
Applicant cites to Table A in the response and argues that “only minor changes to the … [compound structure] … can have significant impact on inhibitory activity against vanin-1” thus it was not predictable that the compounds would share utility.
This argument is not persuasive because the expectation of success need only be reasonable, not absolute. PharmaStem Therapeutics, Inc. v. Viacell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007) (“Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1367-69 (Fed. Cir. 2007) (simply because the formation and properties of a new compound must be verified through testing does not mean that the compound satisfies the test for patentability "since the expectation of success need only be reasonable, not absolute"); In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986) ("Obviousness does not require absolute predictability."). Good science and useful contributions do not necessarily result in patentability.”). In this case, in view of the success of the cited art, one of ordinary skill in the art had a reasonable expectation of success in the application of the bioisosteric approach to arrive at the invention as claimed.
Conclusion
No claims 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.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626