DETAILED ACTION
A non-final Office action was mailed August 18, 2025 (“Office Action”).
Applicant’s reply to the Office Action was received November 17, 2025 (“Reply”).
Status of the Claims
The listing of claims filed with the Reply has been examined.
Claims 2–8 and 10–21 are pending. Claim 1 and 9 are canceled.
Claims 2 and 10 are amended. Claims 3–5, 5–7, and 11–20 are withdrawn.
Status of Rejections and Objections
The text of those sections of Title 35, U.S. Code not included in this action are set forth in the Office Action.
Unless repeated herein, any objection or rejection in the Office Action is withdrawn.
Scope of Search and Examination
Amended claim 2 has been searched and is free of the prior art.
Withdrawn claims 3–5, 5–7, and 11–20 are hereby rejoined. The search and examination are extended to all pending claims.
Claim Interpretation
Claim 2 is directed to, inter alia, compounds of Formulae I and III, which include variable Y1 in a ring structure. By way of amendment, the textual definition of variable Y1 has been deleted; however, variable Y1 is defined as N in the structure of the wherein clause below.
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Claim 18 recites “resistant to other cancer treatment.” The term “resistant” is interpreted to mean the subject did not go into remission after the other cancer treatment. Regarding “other treatment,” the specification states: “The treatment method of the present invention can be administered alone or in combination with other treatment means or therapeutic drugs.” (Spec., 32:7–8) (page:lines). The specification states: “The other cancer therapeutic agents include radiological agents, cytotoxic agents, kinase inhibitors, immune targeting inhibitors, and angiogenesis inhibitors.” (Id., 15:3–5). In view of the specification, the term “other cancer treatment” includes any existing cancer treatment.
Claim Objections
Claims 2 and 13 are objected to for minor informalities. Correction is required.
Claim 2 is directed to, inter alia, compounds of Formulae I and III. The structures are shown in the claim and identified by the corresponding roman numeral; however, the roman numerals are positioned sideways, as pointed out below.
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Claim 13 recites “RET.” Acronyms should be defined in the claims, at least in the first instance, to avoid confusion. For example, “RET” can be amended to “rearranged during transfection (RET).”
Claim Rejections - 35 U.S.C. § 112
Claim 16 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 16 recites: “The compound . . . of claim 2, wherein the hydrogen on Q2 is substituted . . .” (Emphasis added).
Claim 16 refers to claim 2. Claim 2 does not recite “a hydrogen on Q2.”
There is insufficient antecedent basis for using definite article “the” because there is no preceding recitation of indefinite article “a” or “an.” Moreover, because Q2 is a heterocycle that can include a plurality of hydrogens, one of ordinary skill in the art would not be able to understand which hydrogen on Q2 is referred to in claim 16. Accordingly, the lack of antecedent basis for “the hydrogen” renders the claim indefinite.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112
The following is a quotation 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.
Claims 18–20 are rejected under 35 U.S.C. § 112(a) as failing to comply with the written description requirement. The claims contain subject matter that was not described in the Specification in such a way as to reasonably convey to one of ordinary skill in the art that Applicant, at the time the application was filed, had possession of the claimed invention.
In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc), the Federal Circuit stated “the hallmark of written description is disclosure.” A specification adequately describes an invention when it “reasonably conveys to those skilled in the art the inventor had possession of the claimed subject matter as of the filing date.” (Id.). “A ‘mere wish or plan’ for obtaining the claimed invention is not adequate written description.” Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1348 (Fed. Cir. 2011).
What is required to meet the written description requirement “varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). In Ariad, the Federal Circuit explained what is required to meet the written description requirement:
This inquiry, as we have long held, is a question of fact. Ralston Purina, 772 F.2d at 575. Thus, we have recognized that determining whether a patent complies with the written description requirement will necessarily vary depending on the context. Capon v. Eshhar, 418 F.3d 1349, 1357–58 (Fed. Cir. 2005). Specifically, 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. Id. For generic claims, we have set forth a number of factors for evaluating the adequacy of the disclosure, including “the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue.” Id. at 1359.
(Ariad, at 1351).
The written description of a genus, such as a chemical genus, “requires a precise structure, formula, [or] chemical name” of the claimed subject matter sufficient to distinguish it from other materials. Regents of the Univ. of Cal. v. Eli Lilly & Co., 199 F.3d 1559, 1568 (Fed. Cir. 1997). The Federal Circuit commented on that case in the Ariad decision:
We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus. Id. at 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001)). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
(Ariad, at 1350).
The factors outlined in the above Federal Circuit cases are analyzed with respect to the claimed invention in turn below.
The method in claim 18 and composition in claims 19 and 20 are addressed separately.
Claim 18
(A) The nature and scope of the claimed invention in view of the specification: the claimed invention relates generally to the pharmaceutical art and more specifically to a method of treating a “subject [ ] resistant to other cancer treatment” with a composition comprising: a compound of Formulae (I), (III), (V), or (VI). The subject is “in need” of a “RET-related cancer” treatment. (Claim 14). The claim is therefore directed to a patient population of existing cancer patients who have received a cancer treatment but the patent was resistant to such treatment.
The Specification discloses compounds of Formulae (I), (III), (V), or (VI), methods of synthesizing the compounds, and bioactivity testing for compounds C1–C8. (Spec., 33:9–46:20). The Specification does not disclose an example, bioactivity testing, or administration of a compound of Formulae (I), (III), (V), or (VI) to a cancer patient resistant to other treatments.
(B) The extent and content of the prior art: Examiner is not aware of prior art describing the claimed but not described subject matter or otherwise suggesting it would have been known or obvious to one of ordinary skill in the art. Accordingly, Applicant’s disclosure is critical to show possession.
(C) The maturity of the science or technology: subjects who are resistant to cancer treatments exist. But the administration of a compound of Formulae (I), (III), (V), or (VI) to those subjects appears to be novel. As such, the science is in its infancy.
(D) The predictability of the aspect at issue: the pharmaceutical art is generally recognized as unpredictable. In re Fisher, 427 F.2d 833, 839 (CCPA 1970). The art requires each potential drug candidate to be assessed for physiological activity. (Id.). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. In this case, there is no evidence suggesting the claimed invention is more predictable than the pharmaceutical art is generally.
The question of written description
When the above factors and the evidence of record are considered as a whole, the Specification does not adequately describe a method of administering a compound of Formulae (I), (III), (V), or (VI) to a subject who was resistant to other cancer treatments. There are no examples in the specification for such a method. The science is its infancy and unpredictable, and the prior art is not a substitute for disclosure. Accordingly, the Specification would not reasonably convey to those skilled in the art the inventor had possession of the claimed subject matter as of the filing date.
Claims 19 and 20
(A) The nature and scope of the claim invention in view of the specification: the claimed invention relates generally to the pharmaceutical art and more specifically to a composition comprising: (i) a compound of Formulae (I), (III), (V), or (VI) and (ii):
[Claim 19] “a PD-1 inhibitor, a PD-L1 inhibitor, a CD20 antibody, a CD47 antibody, an ALK inhibitor, a PI3K inhibitor, a BTK inhibitor, a VEGFR inhibitor, a HDAC inhibitor, a CDK inhibitor, a MEK inhibitor, an Akt inhibitor, a MTOR inhibitor, a SHP2 inhibitor, an IGF-1R inhibitor, or a combination thereof”; or
[Claim 20] “nivolumab, pembrolizumab, JS-001, SHR-120, BGB-A317, IBI-308, GLS-010, GB-226, STW204, HX008, HLX10, BAT1306, AK105 , LZM 009, devaluzumab, Atezolizumab, CS1001, KN035, HLX20, SHR- 1316, BGB-A333, JS003, CS1003, KL-A167, F520, GR1405, MSB2311, rituximab, obinutuzumab, ofatumumab, tositumomab, titumomab, Hu5F9-G4, CC-90002, TTI-621, TTI- 622, OSE-172, SRF-231, ALX-148, NI-1701, SHR-1603, IBIl88, IMMO1, ceritinib, alectinib, brigatinib, loratinib, okatinib, idelaris, Dactolisib, Taselisib, Buparlisib, ibrutinib, Tirabrutinib, Acalabrutinib, afatinib, gefitinib, erlotinib, lapatinib, dacomitinib, ectinib, Tinib, canetinib, sorafenib, pazopanib, revatinib, carbotinib, sunitinib, donafinib, Givinostat, Droxinostat, entinostat, daxistat, tycdinaline, Pabocinil, Ribocinil, Abemaciclib, Lerociclib, Metinib, trametinib, PD0325901, U0126, AS-703026, PD184352, MK-2206, Ipatasertib, Capivasertib, Afuresertib, Uprosertib, Vistusertib, RMC-4630, JAB-3068, TNO155, Ceritinib, okatinib, linsitinib, BMS-754807, GSK1838705A, or a combination thereof.”
The genus of Formulae (I), (III), (V), or (VI) includes numerous variables (X1, X2, X3, X4, Rx, Q2, B, E, R5, n, etc.) that result in thousands or millions of different compounds based on the number of possible combinations of the variables.
Claim 19 includes a genus of an unknown number of species. There could be dozens, hundreds, or thousands of species within each functionally-defined component (e.g., PD-1 inhibitor). The number of species for each component cannot be determined because a comprehensive list for each recited component is not provided in the specification or elsewhere.
Claim 20 recites about 100 therapeutic agents and “combinations thereof.” A combination can be two agents, three agents, etc. Thus, claim 20 is a genus of thousands of different combinations of agents. When those agents or combinations thereof are combined with a compound of Formulae (I), (III), (V), or (VI), the resulting genus includes millions of possible compositions.
The Specification discloses compounds of Formulae (I), (III), (V), or (VI), methods of synthesizing the compounds, and bioactivity testing for compounds C1–C8. (Spec., 33:9–46:20) (page:line). The Specification does not disclose example, bioactivity testing, or method of preparing a composition comprising a combination of a compound of Formulae (I), (III), (V), or (VI) and one of the agents referenced in claims 19 and 20.
(B) The extent and content of the prior art: Examiner is not aware of prior art describing the claimed but not described subject matter or otherwise suggesting it would have been known or obvious to one of ordinary skill in the art. Accordingly, Applicant’s disclosure is critical to show possession.
(C) The maturity of the science or technology: the compounds of Formulae (I), (III), (V), or (VI) appear to be free of the prior art. As such, there are no examples of a composition comprising the compounds and another agent in the prior art. The science is in its infancy.
(D) The predictability of the aspect at issue: as discussed above, the claimed invention is considered unpredictable.
The question of written description
When the above factors and the evidence of record are considered as a whole, the Specification does not adequately describe a representative number of species to support the claimed invention to a genus of compositions comprising a compound of Formulae (I), (III), (V), or (VI) and another active agent. The science is its infancy and unpredictable, and the prior art is not a substitute for disclosure. There are no examples of the claimed composition, which is a genus of unknown number of species that is estimated to be in the millions. Accordingly, the Specification would not reasonably convey to those skilled in the art the inventor had possession of the claimed subject matter as of the filing date.
Allowable Subject Matter
Claims 2, 13, and 16 are objected to or rejected herein but would be allowable if the formal issues are addressed.
Claims 3–8, 10–12, 14, 15, 17, and 21 are objected to for depending on a claim that is not allowable, but will be allowable when the issue with claim 2 is addressed.
Conclusion
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 C.F.R. § 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 C.F.R. § 1.17(a)) pursuant to 37 C.F.R. § 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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
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The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.M.N./Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623