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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-3, 11 and 12, drawn to compounds, in the reply filed on June 30, 2026 is acknowledged.
Claims 4-10 and 13-20, drawn to methods of treatment (Group II), are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant additionally elects the species of compound 1-bo, without traverse:
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Claims 1-3, 11 and 12 are under examination and are the subject of this office action.
Information Disclosure Statement
6. The information disclosure statements (IDS) submitted on April 26, 2024, September 10, 2024, October 25, 2024, June 18, 2025, September 4, 2025, and April 13, 2026, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner, please refer to the signed copies of Applicant’s PTO-1449 forms, attached herewith.
Claim Objections
7. Claim 11 is objected to because a period is present at the end of the third line of the claim on page 29, rather than a colon.
Claim Rejections - 35 USC § 112(b)
8. 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.
9. Claims 1-3, 11 and 12 are 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.
10. Claim 1 is unclear regarding the limitation: “Z is … a cyclic compound chosen from… [language omitted]” [emphasis added] in line 15, which is confusing because it is not clear if Applicant intends for “Z” to embrace an additional, as yet-unrecited compound, or if the limitation is intended to embrace a cyclic group/ cyclic moiety.
11. Claims 2, 3, 11, and 12 are rejected as being dependent upon, and including all of the limitations of, rejected claim 1.
Claim Rejections - 35 USC § 112(a)
12. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
13. Claims 1-3, 11 and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement regarding the full scope of compounds and alternatives according to the genus of Formula I, including salt, solvates and prodrugs thereof. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. In particular, support cannot be found for the full scope of compounds of Formula I, or their salts, solvates, or prodrugs thereof, as instantly recited by the claims.
14. The MPEP §2163 states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. In the case of chemical entities, Applicant's attention is further directed to Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), which notes that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, “not a mere wish or plan for obtaining the claimed chemical invention.” While the court recognizes that, “[i]n claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass” (Id.), it is also recognized that for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim and/or the genus must be sufficiently detailed to show that applicant was in possession of the claimed invention as a whole (see Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555 (Fed. Cir. 1991)). If a genus has substantial variance, the disclosure must present a sufficient number of representative species that encompass the genus in order to adequately describe the genus (i.e., the disclosure must describe a sufficient variety of species to reflect the variation within that genus). See MPEP § 2163. Otherwise, as stated by the court in Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company (Fed. Cir. 2010), “a generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus.
15. The factors considered in the Written Description requirement are:
(1) level of skill and knowledge in the art,
(2) partial structure,
(3) physical and/or chemical properties,
(4) functional characteristics alone or coupled with a known or disclosed
correlation between structure and function, and
(5) the method of making the claimed invention.
16. Level of skill and knowledge in the art: The level of skill to practice the art of the instantly claimed invention is high and requires a variety of skills usually found in institutions and companies that employ highly trained and skilled scientists to carry out these tasks.
17. Partial structure; Physical and/or chemical properties; and Functional characteristics: The claims are drawn to a compound according to Formula I:
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, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and its pharmaceutical composition. In the instant case, it is evident that the genus of compounds embraced by Formula I has substantial variance. The claimed genus of Formula I is virtually without limit, embracing hundreds of millions of compounds, if not billions, which bear little structural overlap with one another, i.e., presently the genus of compounds according to Formula I embraces compound species wherein the “A” ring embraces any aryl or heteroaryl ring, without limit, that is optionally substituted with any 5-6 membered heterocyclic ring; “Z” embraces any 4-7 membered nitrogen-containing ring, any 7-10 membered nitrogen-containing bridged bicyclic ring; R3 embraces any heteroaryl without limit; R4 embraces any heteroaryl or heteroaryloxy without limit; R6 embraces any 4-7 membered heterocyclic ring without limit; and the ring comprising “X,” “Y,” and “W,” embraces phenyl, pyridyl, or pyrimidinyl. For example, a compound of Formula I wherein “X” and “W” are nitrogen; “A” is naphthyl; and the “L-Z-R2” moiety is -alkoxy-pyrrolidinyl requires entirely different search strategy, parameters and consideration than a compound of Formula I wherein “X,” “Y,” and “W,” are each carbon; “A” is pyridinyl; and the “L-Z-R2” moiety is -aminoalkyl-cyclohexyl.
18. Applicant defines the terms solvate and prodrug in the Specification:
“[0036] The term "solvate" refers to a chemical complex formed by the interaction of a solvent and a solute, such as the chemical compounds of the present invention.
[0037] The term "prodrug" refers to a biologically inactive compound which can be metabolized inside or outside the body to produce a drug.”
Regarding the term “prodrug,” while it is known in the art that a prodrug is a compound that, after administration, is converted into an active drug, the Specification
but fails to describe examples of such. The instantly recited compounds would presumably have multiple sites of possible cleavage for prodrug activation, i.e., any -OH or -NH moieties, for example. However, Applicant is silent as to specific prodrugs or solvates of the instant invention.
19. The instant compounds are alleged by the Specification to be KRAS oncoprotein inhibitors, which may be useful as therapeutics for the treatment of certain cancers including non-small cell lung cancer, colorectal cancers, pancreatic ductal adenocarcinomas, and small cell lung cancers, for example (paragraph [0003]).
20. Method of making: It is evident that the genus of compounds embraced by the claims has substantial variance, for example, the variables “A” ring embraces any aryl or heteroaryl ring that is optionally substituted with any 5-6 membered heterocyclic ring; “Z” embraces any 4-7 membered nitrogen-containing ring, any 7-10 membered nitrogen-containing bridged bicyclic ring; R3 embraces any heteroaryl; R4 embraces any heteroaryl or heteroaryloxy; R6 embraces any 4-7 membered heterocyclic ring, such that the scope of compounds of Formula I recited by claim 1 embraces hundreds of millions of possible compound species, as well as their solvates, pharmaceutically acceptable salts and prodrugs thereof. Yet, the instant Specification discloses the preparation of only about 15 compound species corresponding to instant Formula in the syntheses of the following compound species according to claimed Formula I: compounds 2a, 2b, 2c (Scheme 2), compounds 3a, 3b, 3c (Scheme 3), compound 4 (Scheme 4), compounds 5a and 5b (Scheme 5), compounds 6a, 6b, 6c (Scheme 6) and 7a, 7b, 7c (Scheme 7) at pages 42-50.
21. While the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad generic claim. For example, in In re Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d 1008 (Fed. Cir. 1989). In the instant case, it is similarly determined that the disclosure of the preparation of about fifteen compounds in Schemes 1-7 does not adequately describe a genus embracing hundreds of millions of possible compounds. That is, the Specification does not disclose a sufficient variety of species to reflect the breadth of the possible compound selections recited in the claims.
22. The level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172; Capon v. Eshhar, 418 F.3d 1349, 1357-58, 76 USPQ2d 1078, 1083-84 (Fed. Cir. 2005). The fields of biology and chemistry are considered “unpredictable” because the complexity and unpredictability of chemical and biological interactions can make it difficult to understand the exact properties of an invention. The pharmaceutical industry is the prototypical example of a highly unpredictable field. Pfizer v. Teva Pharm., 482 F.Supp.2d 390, 413 (D.N.J. 2007); 2 Chisum on Patents § 5.04.
23. Applicants have failed to provide guidance or data or evidence as to how the skilled artisan would be able to extrapolate from the disclosure to use the claimed invention. “A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F 3d at 923; Eli Lilly, 119 at 1568. Instead, the “disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described.” Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
24. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521,222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
25. Accordingly, it is deemed that the specification fails to provide adequate written description for the full scope of compounds of Formula I or a pharmaceutically acceptable salt, solvate, or prodrug thereof and its pharmaceutical composition thereof, as recited in the claims, and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
As such, claims 1-3, 11 and 12 are rejected.
Claim Rejections - 35 USC § 102/ 103
26. 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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
27. 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.
28. 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.
29. Claims 1-3, 11 and 12 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by or, in the alternative, under 35 USC 103 as obvious over Kawai et al., WO 2021/107160 A1 (published June 3, 2021).
Claim 1 is drawn to fused pyrimidine compounds of Formula I, having inhibitory activity at KRAS 12D:
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, in particular wherein “X,” “Y,” and “W” are each CR5 wherein R5 is H, alkyl, or halogen; the “A” ring embraces naphthyl optionally substituted by hydroxy; R1 is H; L is O; n is 1; Z is C3-4 cycloalkyl; and R2 is -CH2-R6 wherein R6 is -N(R3)2 wherein R3 is methyl.
30. Kawai et al. teach a genus of fused pyrimidine compounds according to formula (1), that also have inhibitory activity at the KRAS G12D mutation, in particular compounds 14-19 which read on Applicant’s instantly claimed genus of Formula I:
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(Table 1, pages 152-154).
Thus, when the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. See Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying that "the tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is ‘described’ as that term is used in [pre-AIA ] 35 U.S.C. 102(a), in that publication."). Id. at 1718.
As such, claim 1 is anticipated.
31. In the alternative, claims 1-3, 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Kawai et al., WO 2021/107160 A1.
Claims 2 and 11 are drawn to claim 1, and limit the compound species of Formula I.
Claims 3 and 12 are drawn to a pharmaceutical composition comprising a compound of claim 1.
32. Kawai et al. teach a genus of functionally related fused pyrimidine compounds according to formula (1), that have inhibitory activity at the KRAS G12D mutation:
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(pages 1-5).
33. The genus of compounds disclosed by Kawai et al. fully encompasses Applicant’s instant compounds and demonstrate activity as KRAS 12D inhibitors (paragraph [0035]). Kawai et al. generically demonstrate that the “B” ring fused to the pyrimidine can be phenyl, pyridyl or pyrimidinyl; and wherein ring “A” is an 8-membered bridged ring containing at least one further heteroatom that can be N; and wherein “Y” corresponds to Applicant’s “A” ring and can be a 6-10 membered aryl or heteroaryl ring (including naphthyl); and wherein “L” can be O and “Z” can be C3-C6 cycloalkyl or C5-C10 heterocycloalkyl, which embrace Applicant’s instant compound species recited in claims 2 and 3. Kawai et al. go on to teach a pharmaceutical composition comprising a compound of formula (1) in paragraph [19].
34. Regarding the comprehensive of the genus disclosed by Reddy et al., a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. "The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.").
32. Additionally, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
33. Thus, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
33. Therefore, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention in view of the teachings of Kawaii et al. to prepare Applicant’s compounds of claims 2 and 12, having the same core structure and sharing the same utility of inhibiting KRAS 12D, with a reasonable expectation of success.
As such, claims 1-3, 11 and 12 are also prima facie obvious.
Conclusion
34. Claims 1-20 are present in the application. Claims 4-10 and 13-20 are withdrawn. Claims 1-3, 11 and 12 are rejected. Claim 11 is objected to. No claim is presently allowed.
35. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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