DETAILED NOTICE
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
The present Application, filed June 2, 2023, is a national stage entry under 35 USC § 371 of International Patent Application No. PCT/CN202l/135247, filed December 3, 2022, which claims the benefit of U.S. Provisional Patent Application No. 63/121,300, filed December 4, 2020.
Status of the Claims
In the amendment filed, claim 84 is canceled and new claim 128 is added. Claims 1 and 85 are amended. Claims 2-26, 29-47, 49-61, 70-76, 79-83, 88-115, and 120-127 were previously canceled. Claims 1, 27-28, 48, 62-69, 77-78, 85-87, 116-119, and 128 are currently pending.
Response to Amendments/Arguments
Claim Objections:
The amendments to claims 4, 7, and 8 resolve the objections to these claims, and the objections to claims 4, 7, and 8 are withdrawn.
Rejections for Indefiniteness:
The amendment to claim 1 resolves the rejections of claims 1, 84-87, and 117-119 under 35 U.S.C. § 112(b) for indefiniteness, and these rejections are withdrawn.
Rejections for Failure to Include All Limitations of the Base Claim:
In its remarks of May 18, 2026, Applicant notes that Formula (IX) of claim 27 is properly a sub-genus of Formula III of claim 1, in particular where Y is a bond. The rejection erroneously overlooked the fact that Y can be a bond. In view of this, the rejections of claims 27 and 62-65 under 35 U.S.C. § 112(d), for alleged failure to incorporate all limitations of their base claim(s), are withdrawn.
Rejections for Anticipation:
The amendment to claim 1 overcomes the previous rejections of claim 1 and its dependent claims, 27-28, 62-63, 66-67, and 117-119 for anticipation under 35 U.S.C. § 102(a)(1).
Claim Rejections - 35 USC § 102 – Modified in View of Amendment
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 28, 117, and 128 are anticipated by Adam:
Claims 1 and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent No. 8,227,613 to Adam et al. (hereinafter, “Adam”).
Claim 1 recites a compound of Formula (XLII) or (III):
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where the variable groups are as defined.
Adam teaches compounds, useful as antagonists of C-C motif chemokine receptors, having a formula (I)
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where the variable groups are as defined (col. 1, line 60 through col. 4, line 15). In a working example, Adam teaches Example 24
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col. 59, lines 35-55), which is a compound of instant claim 1 (Formula III), where R1 is H; U is −N=; X, Y and Z are -C(R2a)= with R2a being methyl, H, and phenyl (C6 aryl), respectively, the phenyl being substituted with one substituent Q that is methyl (C1 alkyl) and the C1 alkyl being substituted with three substituents Qa that are fluorine (halo); R1 is H; A is −C(O)−; L1 is piperidinylene (heterocyclylene); L2 is pyrrolidinylene (heterocyclylene); and R3 is H. Claim 1 is therefore anticipated.
With respect to claim 28, Example 24 of Adam is a compound of Formula (XII) with R1, A, L1, L2 and R3 as defined above; with U being −N=, Z being −C(H)−, and each R2a being hydrogen.
With respect to claim 117, Adam teaches pharmaceutical compositions comprising a disclosed compound (e.g. Example 24) and a pharmaceutically acceptable excipient (col. 37, lines 33-35). With respect to claim 128, the group corresponding to instant R1 in Example 24 of Adam is H.
Claims 1 and 27 are anticipated by Zhao:
Claims 1 and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent Application Publication No. 2019/0263808 to Zhao et al. (hereinafter, “Zhao”).
Zhao teaches antagonists of αv-containing integrins (Abstract) a generic formula I (not shown here). In a working example, Zhao teaches compound 152B, a synthesis intermediate.
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Compound 152B is a compound of instant Formula (III) where R1 is methyl (C1 alkyl) substituted with a substituent Q that is ethyl (C2 alkyl) that is further substituted with a substituent Qa that is −ORa where Ra is H; U is −N=, X is −C(R2a)= where R2a is H, Y is a bond, and Z is −S−; A is −C(O)−; L1 is a bond; L2 is phenylene (arylene) that is further substituted with a substituent Q that is fluoro (halo); and R3 is −C(O)OR1a where R1a is methyl (C1 alkyl).
Claim 27 recites a compound of Formula (IX)
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where the variable groups are as defined.
Zhao compound 152B is a compound of instant Formula (IX) where R1, R2a, A, L1, L2, and R3 are as described above in the mapping of compound 152B to Formula (III).
Claim Rejections - 35 USC § 103 – Necessitated by Amendment
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.
Claims 118-119 are unpatentable over Adam:
Claims 118-119 are rejected under 35 U.S.C. 103 as being unpatentable over Adam.
Claim 118 recites a method of treating a proliferative disease in a subject comprising administering to the subject in need thereof the compound of claim 1. Claim 119 recites a method of treating a disorder, disease, or condition mediated by a glutathione peroxidase 4 in a subject, having the same method step.
Adam is applied to claims 118 and 119 as to claim 1, above. Adam further teaches that the disclosed compounds (e.g. Example 24) can be used for the treatment and/or prevention of a variety of diseases, such as restenosis (col. 37, lines 16-29). Restenosis is properly understood as a “proliferative disease.” See, for example, the non-patent publication, Vascular Smooth Muscle Cell Proliferation in Restenosis, Circulation: Cardiovascular Interventions, 4, pgs. 104-111 (2011) by Marx et al. It thus would have been at least obvious to administer a disclosed compound of Adam, such as Example 24, to a patient in need of treatment for a disease such as restenosis (a proliferative disease) in order to treat said proliferative disease.
The same paragraph of Adam teaches that multiple sclerosis as one of the diseases to be treated by the disclosed compounds. Multiple sclerosis is reasonably regarded as a GPX4-mediated disease. See, for example, the non-patent publication, GPX4 aggravates experimental autoimmune encephalomyelitis by inhibiting the functions of CD4+ T cells, Biochem. Biophys. Res. Commun., 642, pgs. 57-65 (2023) by Li et al. (hereinafter, “Li”). Li teaches experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, that GPX4 is highly expressed in CD4+ T cells of MS patients, and that conditional knockout of GPX4 in model mice significantly alleviated symptoms and immunopathology of EAE (Abstract). Li thus teaches a therapeutic strategy of targeting GPX4 in immune cells to treat MS. On the basis of the teachings of Adam, it would have been obvious to administer Adam Example 24 to a subject in need of treatment for multiple sclerosis (a GPX4-mediated disease), in order to treat multiple sclerosis. Claims 118 and 119 are thus obvious over Adam, given that restenosis and multiple sclerosis are a proliferative disease and a GPX4 mediated disease, respectively.
Allowable Subject Matter
Claims 48, 62-69, 77-78, and 85-87 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Claim 116 is allowed.
Conclusion
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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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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