DETAILED ACTION
This office action is in response to applicant’s filing dated January 5, 2026.
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 .
Status of claims
Claims 1-3, 5-7, 9, 10, 12, 16-18, 22, 30, 31, 36, 40-42, and 44 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of Group I and Group III inventions combination in the reply filed on January 5, 2026 is acknowledged.
Claims 31, 36 and 44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 5, 2026.
Applicant’s election without traverse of compound 1a
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2-[(2-amino-4-pyridinyl)amino]-6-(3-methoxyphenyl)-4(3H)-pyrimidinone as a single species of compounds of Formula Ia in the reply filed on January 5, 2026 is acknowledged.
Claims 5 - 7, 9, 10, 12, 16 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 5, 2026.
Claims 1 – 3, 18, 22, 30 and 40 – 42 are under consideration in the present office action, as related to elected species, compound 1a.
Priority
The present application is a 371 of PCT/US2021/059667, filed November 17, 2021 and claims the benefits of priority of U.S. Provisional application No. 63117336, filed November 23, 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/02/2023 and 01/24/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
Acknowledgement is made of the drawings received on May 22, 2023.
The drawings are objected to because images depicted on Fig.2 and Fig. 9 are blurry, which makes structures and structure labels hard or impossible to see. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 1 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.
Regarding claim 1, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The claim also recites the term “preferably”, which is equivalent to phrase “such as”, renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 – 3, 18, 22, 30 and 40 – 42 are rejected under 35 U.S.C. 103 as being unpatentable over Kalleda et al (WO 2006/034473 A2, hereinafter Kalleda) in view of Galvão et al (J. Phys. Chem. A 2013, 117, 12668−12674, hereinafter Galvão).
Regarding claims 1 – 3, 22, 30 and 40 and 42, drawn to a method of treating, preventing or reducing neuropathic pain in a patient, comprising administering a formulation, comprising compounds of Formula I
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, such as compound of Formula Ia
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, having a structure
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, where X and Y is carbon, Z is nitrogen and R3 is absent. According to the description above, compound of Formula Ia has a structure of substituted 3H‐pyrimidin‐4‐one:
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, where R1 is hydrogen, R2 is unsubstituted or substituted aryl or heteroaryl or R2 is NR5R6, where R5 is hydrogen, and R6 is hydrogen, unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl; R4 is substituted aryl or substituted heteroaryl. One of the exemplary compounds of Formula Ia is compound 1a
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. Instant claims are further drawn to a compound, having a structure according to Formula I, such as to Formula Ia and a formulation comprising compound of Formula Ia and a pharmaceutically acceptable carrier.
Kalleda teaches substituted pyrimidine compounds and pharmaceutical compositions thereof, where the composition comprises substituted pyrimidine compounds and a pharmaceutically acceptable carrier (page 181, lines 15 – 17). Kalleda further teaches a method of treating a condition or disease state mediated by the low expression of Perlecan, such us a neuritis or multiple sclerosis (page 158, line 15 and 159, line 25), comprising administering an amount of at least one of said compound, effective to induce Perlecan expression (page 135, lines 17 – 19). Effective amounts are administered to humans and animals in dosages that are safe and effective (page 160, lines 27 – 29). The substituted pyrimidine compounds taught by Kalleda have a structure such as (II-H1):
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, where R1 is hydrogen, substituted or unsubstituted aryl or substituted/unsubstituted heteroaryl, where heteroaryl comprises at least one heteroatom selected from N, O, S; R2 is hydroxyl; R4 is substituted or unsubstituted alkyl, aryl, heterocyclyl, heteroaryl, where heteroaryl or heterocyclyl comprises at least one heteroatom selected from N, O, S; when R1 or R4 is substituted, the substituents are selected from alkyl, alkoxy (e.g. -OMe), -NR102 (R10 is hydrogen), (page 48, lines 1 – 25 and page 49, lines 1 – 3). The exemplary compound of Formula (II-H1) taught by Kalleda is:
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(page 121, Table 2). Exemplary structure taught by Kalleda satisfies the structure of compound of formula Ia of instant claims, when is R2 is NR5R6 and R5/R6 are both hydrogens; R4 is substituted aryl. Kalleda also teaches compound of formula
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, where A, B and C variables are given in Table 3 (page 144 – 146), which structures satisfy the instantly claimed compounds encompassed by formula Ia.
Although compounds of Kalleda drawn in the hydroxy form of pyrimidine ring and compounds of instant claims are drawn in the keto form, the compounds of instant claims and compounds of Kalleda have the same core structure, since it is well known that 4-hydroxypyrimidine and 4(3H)-pyrimidinone are two tautomeric forms, existing in keto−enol tautomeric equilibrium as shown in the reference of Galvão:
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(page 12668, Fig. 1). Thus, compound of Formula Ia of instant claims can be redrawn in its enol form as:
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.
Regarding limitations of claim 18, drawn to a method where the effective amount is sufficient to inhibit phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) compared to a control that does not contain the compound of Formula I, as determined by an in-cell Western assay that detects inhibition of VEGFR2 activation, The prior art is silent regarding "inhibition of phosphorylation of (VEGFR2)". However: " inhibition of phosphorylation of (VEGFR2) " will naturally flow from the teachings of (or method made obvious by) the prior art (see above rejection), since the same compound (compound of formula (II-H1) is being administered to the same subjects (subjects suffering from neuritis). In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
In other words, even though the prior art is silent regarding " inhibition phosphorylation of (VEGFR2)", by practicing the method made obvious by the prior art: "the administration of an effective amount of compound of formula (II-H1) to a patient suffering from neuritis", one will also be "inhibiting phosphorylation of (VEGFR2) ", even though the prior art was not aware of it.
Apparently, Applicant has discovered a new property or advantage ("inhibition of phosphorylation of (VEGFR2)" of the method made obvious by the prior art ("the administration of an effective amount of compound of formula (II-H1) to a patient suffering from neuritis").
MPEP 2145 II states: "The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art, cannot be the basis for patentability when the differences would otherwise be obvious". Ex parte Obiaya, 227 USPQ 58, 60. (FP 7.37.07, MPEP 707.07(f)).
Regarding limitations of claim 41, which recites exemplary compounds of Formula (I), although Kalleda does not explicitly teach the same exemplary structures, however, Kalleda teaches all the structural elements of the molecule of instantly claimed compounds.
Thus, since Kalleda teaches compounds, which compounds have the same core and all the structural elements as instantly claimed compounds, and where the compounds taught by Kalleda are useful for the same method (method of treating neuritis), it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify teachings of prior art and make various known compounds useful for the same method, to arrive at claimed compounds. The one of ordinary skills would be motivated to do so in search of an active agent with improved desired properties to treat neuritis with the reasonable expectation of success.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
Claims 1 – 3, 18, 22, 30 and 40 – 42 are rejected. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELENA V VISHNYAKOVA whose telephone number is (571)272-3781. The examiner can normally be reached 7:30am - 5pm ET.
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/E.V.V./ Examiner, Art Unit 1691
/SAVITHA M RAO/ Primary Examiner, Art Unit 1691