DETAILED ACTION
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
Applicant' s claim for the benefit of prior-filed applications, Application N° 63/622,680, filed 19 January, 2024 and Application N° 63/609,562, filed 13 December, 2023, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
As of 5 October, 2026, Applicants have not filed an Information Disclosure Statement.
Status of the Application
Receipt is acknowledged of Applicant's claimed invention, filed 10 April, 2025, in the matter of Application N° 18/980,378. Said documents have been entered on the record.
Claims 7-10, 13-14, 16, 18, 22, 25-26, 28-29, 31-32, 34, 36-37, 45, and 48-49 are amended. Claims 2-6, 11-12, 15, 17, 19-21, 23-24, 27, 30, 33, 35, 38-44, 46 and 51-59 are canceled. No new matter was introduced.
Thus, Claims 1, 7-10, 13-14, 16, 18, 22, 25-26, 28-29, 31-32, 34, 36-37, 45, and 47-50 represent all claims currently under consideration.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 16 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 16 recites the limitation “R11, R12, R13, R14, R21, R22, R23, and R24 are each…” in Line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 16 depends from Claim 1 which neither recites nor depicts these structural positions.
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.
Claims 1, 7, 37 and 48-50 are rejected under 35 U.S.C. 103 as being unpatentable over Bebbington et al. (WO 02/22602 A2), hereinafter Bebbington, in view of Ritchie and MacDonald (European Journal of Medicinal Chemistry 124, 2016, 1057-1068.)
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Regarding Claims 1, 7 and 37, Bebbington teaches Compound D18 (‘602, Pg 246), shown top right, which significantly overlaps instant Formula I, shown middle right, wherein A is phenyl (aryl, as in instant Claims 1 and 37), X1 is CH (as in instant Claim 7), and Q is H.
Bebbington’s Compound D18 differs from the instant Formula I in: (i) R1 is H, and (ii) contains an additional ring nitrogen, providing a pyrimidinone rather than the claimed pyridone scaffold.
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While the instant R1 selection does not include H, Bebbington further teaches genus D (‘602, Pg 245, Line 10), which allows halide substituents for that ring, as is exemplified in Compound D7 (‘602, Pg 246), shown bottom right.
It would have been prima facie obvious to one of ordinary skill in the art to modify Compound D18 of Bebbington to include a halogen substituent at the position corresponding to R1 because Bebbington itself teaches that substituents including halogen are suitable at that position and exemplifies such substitution in Compound D7. One of ordinary skill therefore would have had reason to select a halogen at this position as one of the expressly taught substituent alternatives, with a reasonable expectation of obtaining another compound within Bebbington’s disclosed genus.
Bebbington further demonstrates that variation in the number and position of ring nitrogen atoms was contemplated in the design of its heterocyclic kinase inhibitors, expressly disclosing related ring systems in which positions within the heterocyclic scaffold may independently comprise carbon or nitrogen (e.g., ‘602, Pg 6, Ring A alternatives in Lines 15-20).
Consistent with Bebbington’s disclosure of heteroatom variation, Ritchie and MacDonald (2016) teach that heteroaromatic ring identity, including the number and arrangement of ring heteroatoms, influences drug relevant properties, and that investigation of alternative heterocyclic ring systems was a known strategy for evaluating and optimizing drug relevant properties (2016, Abstract, Figs 4 and 6, Table 5, and Conclusion).
Accordingly, one of ordinary skill in the art would have had reason to investigate the corresponding pyridone analog of Bebbington’s pyrimidinone Compound D18 by replacing one ring nitrogen with carbon, because Bebbington itself demonstrates the use of carbon/nitrogen variation within related heterocyclic kinase-inhibitor scaffolds, while Ritchie and MacDonald teach investigation of alternative heteroaromatic ring systems, including changes in heteroatom number and arrangement, as a strategy for optimizing drug-relevant properties, with a reasonable expectation that such a closely related heterocyclic analog could be prepared and evaluated using routine medicinal chemistry methods.
Regarding Claim 48, Bebbington further teaches pharmaceutical compositions comprising the compound and a pharmaceutically acceptable carrier (‘602, Abstract and Pg 17, Lines 7-11).
Regarding Claims 49-50, Bebbington teaches a method of treating cancer, including colon and ovarian comprises administering to a patient in need of such a treatment a therapeutically effective amount of the compound (‘602, Abstract, Pg 18, Line 12-27).
Claims 1, 7, 9-10, 25-26, 28-29, 31-32, 37, 45, and 47-50 are rejected under 35 U.S.C. 103 as being unpatentable over Lindstrom et al. (WO 2019038387 A1), hereinafter Lindstrom, in view of Patani and LaVoie (Chem. Rev. 1996, 96, 3147-3176).
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Regarding Claims 1, 7, 26, 28, 29 and 45, Lindstrom teaches Methyl N-[4-[2-oxo-6-[3-(trifluoromethyl)morpholin-4-yl]-1H-pyridin-4-yl]-2-pyridyl]carbamate ('387, Pg 55, Example 45, and Pg 81-83, Claims 22-24), shown top right, which significantly overlaps instant Formula I, shown middle right, wherein A is morpholino substituted with CF3 (heterocyclyl, as in instant Claim 45), X1 is CH (as in instant Claim 7), and Q is -NHC(O)LR4 (as in instant Claim 25) wherein L is a bond and R4 is methoxy (as in instant Claims 26, 28-29 and 32).
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Similarly, Lindstrom teaches N-[4-[2-(2-methyl-3-pyridyl)-6-oxo-1H-pyridin-4-yl]-2-pyridyl]acetamide (‘387, Pg 51, Example 38, and Pg 80, Claim 22), shown bottom right, which significantly overlaps instant Formula I, wherein A is pyridyl substituted with methyl (heteroaryl, as in instant Claim 37), X1 is CH (as in instant Claim 7), and Q is -NHC(O)LR4 (as in instant Claim 25) wherein L is a bond and R4 is methyl, or alternatively could be interpreted as, L is methylene/alkyl (as in instant Claim 31) and R4 is H (as in instant Claims 26 and 28-29).
Lindstrom’s Examples 38 and 45 differs from instant Formula I in that the position corresponding to R1 is unsubstituted (i.e., bears a hydrogen), whereas instant R1 does not encompass hydrogen.
However, Patani and LaVoie disclose a direct adaptation of Grimm’s Hydride Displacement Law which teaches a monovalent group of isosteres, namely fluorine, hydroxyl, amino, or methyl groups as replacements for hydrogen (1996, Pg. 3152, §4, and Table 9), which share similar physicochemical properties.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to modify the Lindstrom compounds by substituting the hydrogen at the instant R1 position with a fluorine or methyl (as in instant Claims 1 and 9-10), as taught by Patani and LaVoie, in accordance with Grimm’s Hydride Displacement Law. One would have had a reasonable expectation of success because Patani and LaVoie explicitly teach that interchanging hydrogen for fluorine, constitutes a routine substitution yielding compounds with comparable physicochemical and biological properties.
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Regarding Claim 47, Lindstrom’s Example 45 further closely corresponds to the species 36 (instant Claim 47, Pg 9, 2nd Row, 4th Structure), differing in that Lindstrom’s compound bears hydrogen at the corresponding ring position whereas Species 36 bears a methyl.
As discussed above, Patani and LaVoie teach methyl as a known isosteric replacement for hydrogen in accordance with Grimm’s Hydride Displacement Law. It would therefore have been prima facie obvious to one of ordinary skill in the art to modify Lindstrom’s Example 45 by replacing hydrogen at that position with methyl, as taught by Patani and LaVoie, as a known isosteric substitution for obtaining an analog having similar physicochemical properties, with a reasonable expectation of successfully obtaining the corresponding methyl-substituted analog.
Regarding Claim 48, Lindstrom teaches a pharmaceutical composition comprising a compound according to the present invention, and a pharmaceutically acceptable diluent, carrier and/or excipient (‘387, Pg 15, Lines 29-31).
Regarding Claim 49, Lindstrom teaches a method of treating cancer, comprising administering a therapeutically effective amount of a compound according to the present invention, to a patient in need thereof (‘387, Pg 14, Lines 12-14).
Regarding Claim 50, Lindstrom further teaches said cancer is selected from breast cancer, such as triple negative breast cancer, bladder cancer, liver cancer, cervical cancer, pancreatic cancer, leukemia, lymphoma, renal cancer, colon cancer, glioma, prostate cancer, ovarian cancer, melanoma and lung cancer, as well as hypoxic tumors (‘387, Pg 14, Lines 14-18).
Allowable Subject Matter
Claims 8, 13-14, 18, 22, 34 and 36 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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Donna M. Nestor whose telephone number is (703)756-5316. The examiner can normally be reached generally (w/flex): 5:30a-5p EST M-Th.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.M.N./Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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