DETAILED ACTION
A non-final Office action was mailed 30 October 2025 (“Office Action”).
Applicant’s reply to the Office Action was received 9 February 2026 (“Reply”).
Status of the Claims
The listing of claims filed with the Reply has been examined.
Claims 1–11 are pending. No claims have been amended.
Status of Rejections and Objections
The text of those sections of Title 35, U.S. Code and/or text providing the basis for non-statutory double patenting rejections 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Unless repeated herein, any objection or rejection in the Office Action is withdrawn.
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.
(i) Claims 1–7 and 10 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.
(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] method of treating a prostate cancer in a subject, wherein the prostate cancer comprises at least one pathogenic androgen receptor mutation (emphasis added).”
Claims 8 and 9 define the “at least one pathogenic androgen receptor mutation” as L702H, H875Y, and/or T878A. Those claims are omitted from this rejection.
The Specification states, “we have identified that subjects with prostate cancer having pathogenic androgen receptor (AR) mutations who are [sic] have been treated with enzalutamide have a lower average progression free survival while undergoing treatment with [sic] than their corresponding wild-type treated counterparts.” (Spec., ¶8).
The specification states: “Pathogenic androgen receptor (AR) mutations include those mutations that increases a subject’s susceptibility or predisposition to that prostate cancer, or which decreases a subject’s susceptibility, predisposition, or response to hormonal therapies such as treatment with an ARSI. Pathogenic AR mutations can occur in the ligand binding domain or the transactivation domain, or both, of the AR receptor.” (Id., ¶20).
The specification discloses the following androgen receptor mutations: W742L, A491R fs, S522R, L638V, L702H, H875Y, T878A, and F877L. (Id.).
Based on the claim language and disclosures in the specification, the phrase “the prostate cancer comprises at least one pathogenic androgen receptor mutation” refers to the patient population (or subjects), which are characterized by their form of prostate cancer.
The specification does not explain the number of AR mutations that fall within the scope of the claimed genus (“at least one pathogenic androgen receptor mutation”). Further, because multiple AR mutations are possible (the claim states “at least one pathogenic androgen receptor mutation”), there can be combinations of AR mutations that multiply the number of AR mutations (or patient populations) falling within the scope of the claimed genus.
(B) The extent and content of the prior art: Chen et al., Scientific Reports (21 July 2020), 10:12101, pp.1–13 (“Chen”) states, “more than 1,000 AR mutations have been identified.” (Chen, p.2). Because multiple AR mutations are possible, there can be combinations of the “more than 1,000 AR mutations” that multiply the number of AR mutations within the scope of the claimed genus (i.e., thousands or millions of possible subject profiles).
(C) The maturity of the science or technology: the compounds in the claimed method are known (e.g., formula in claim 1; enzalutamide in claim 4), and methods of using the claimed compounds to treat prostate cancer are known. Thus, the science is generally mature; however, the claimed method features one or more subsets of the general patient population (“the prostate cancer comprises at least one pathogenic androgen receptor mutation”) that has a lower survival rate and that method appears to be in a relatively infant stage of development.
(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 evidence are considered as a whole, the specification (in view of the prior art) does not adequately describe a representative number of species to support the scope of the claimed method because the specification discloses 8 AR mutations out of over 1,000 mutations, the science is in a relatively infant stage of development for the specifically claimed patient population, and the issues addressed in the claimed method are unpredictable in nature. 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.
Examiner recommends amending independent claim 1 to recite the specific androgen receptor mutations disclosed in the specification.
(ii) Claims 2 and 11 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.
The factors outlined in the above Federal Circuit cases are analyzed with respect to the claimed invention in turn below.
(A) The nature and scope of the claim invention in view of the specification: the invention in claim 2 is directed to a method of treating a prostate cancer in a subject, wherein the prostate cancer comprises at least one pathogenic androgen receptor mutation, comprising administering the compound in claim 1 in combination with an androgen receptor signaling inhibitor (ARSI). Claim 11 relates to a composition comprising the compound shown in claim 11 in combination with an androgen receptor signaling inhibitor.
The scope of the claimed ARSI is not limited by chemical name or structure. Rather, the scope is based on functionality and includes any compound having any ability to “block the androgen receptor (AR) and inhibit or suppress androgen production.” (Spec., ¶23). The application discloses 7 examples of ARSI: bicalutamide, enzalutamide, apalutamide, flutamide, nilutamide, darolutamide, and abiraterone acetate. One of ordinary skill in the art would appreciate that numerous derivatives of each of the ARSI compounds could be prepared while still maintaining at least some ability to “block the androgen receptor (AR) and inhibit or suppress androgen production.” While the number of compounds encompassed within that scope is unknown, it potentially includes hundreds to thousands of compounds.
(B) The extent and content of the prior art: bicalutamide, enzalutamide, apalutamide, flutamide, nilutamide, darolutamide, and abiraterone acetate are known ARSI; however, it is unknown how many other ARSI there are.
(C) The maturity of the science or technology: a combination therapy comprising the claimed compound and an ARSI appears to be in a relatively infant stage of development.
(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 evidence are considered as a whole, the specification (in view of the prior art) does not adequately describe a representative number of species to support the scope of the claimed ARSI because the application discloses only 7 ARSI compounds out of possibly hundreds or thousands of compounds capable of the function; the science is in a relatively infant stage of development; and the issues addressed in the claimed method are unpredictable in nature. 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.
Examiner recommends amending independent claim 1 to recite the specific ARSI listed in claim 3.
Claim Rejections - 35 U.S.C. § 103
(i) Claims 1 and 5–10 are rejected under 35 U.S.C. § 103 as being unpatentable over WO2019/204490 (“Cote”) [IDS] in view of Scher et al., The New England Journal of Medicine (2012), 367(13), 1187–1197 (“Scher”), Luo et al., Int’l Journal of Cancer (2018), 142, 2163–2174 (“Luo”), WO2014/172431 (“Raymon”), and Fujita et al., World J. Mens Health (2019), 37(3), 288–295 (published 10 September 2018) (“Fujita”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
Cote discloses the compound claimed in the instant application (“Example 17”):
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. (Cote, ¶¶171; 178; claim 15).
Cote discloses pharmaceutical compositions comprising Example 17. (Id., ¶¶6; 8; 49–58; claims 21).
Cote discloses methods of treating cancer, including prostate cancer, with the pharmaceutical composition and Example 17. (Id., ¶¶4; 8; 57–61; claims 22–23).
Cote discloses treating EZH2 and mutants thereof. (Id., ¶¶5; 49–55).
Cote discloses the use of a drug combination including Example 17. (Id., ¶52).
Scher discloses a method of treating prostate cancer with enzalutamide in combination with chemotherapy in patients with castration-resistant prostate cancer. (Scher, Title; p.1187).
Scher states, “Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant.” (Id., p.1187).
Scher states: “Patients were eligible for enrollment if they had a histologically or cytologically confirmed diagnosis of prostate cancer, castrate levels of testosterone (<50 ng per deciliter [1.7 nmol per liter]), previous treatment with docetaxel, and progressive disease defined according to PCWG2 criteria (see the Study End Points section below), including three increasing values for prostate specific antigen (PSA) or radiographically confirmed progression with or without a rise in the PSA level.” (Id., 1188).
Scher states: “These data confirm the central role of the androgen receptor and androgen-receptor signaling in the progression of prostate cancer throughout the spectrum of disease.” (Id., p.1194).
Luo discloses a combination therapy with enzalutamide and CCX771 (a chemokine receptor CXCR7 inhibitor) is more effective than single agents for reducing the levels of p-EGFR (Y1068), p-AKT (T308), and VEGFR2. (Luo, Abstract, pp.2167–2172).
Luo summarizes the results of the study as follows: “in this study we demonstrated that ENZ treatment enhanced the downregulation of p-EGFR, p-AKT, VEGFR2 and secreted VEGF when combined with a CXCR7-specific inhibitor, CCX771, in VCaP and C4-2B PCa cells . . . we showed that ENZ and CCX771 combination treatment was more effective in suppressing migration compared to single agent treatment than ENZ and AMD3100 combination treatment. Importantly, ENZ and CCX771 combination treatment showed significantly greater growth suppression activities in PCa cell line xenograft and PDX models of CRPC, and an analysis of tumor tissues showed a significant reduction in the large tumor-associated vessels in response to this combination treatment. However, this was not the case with single agent treatment.” (Id., p.2173).
Raymon discloses a method of treating prostate cancer with a combination of a pyrazine compound and an androgen receptor antagonist. (Raymon, ¶¶2; 11–14; 113–119; 121; 137–145).
Raymon discloses the androgen receptor antagonist is enzalutamide. (Id., ¶112).
Fujita states: “Point mutations in the AR gene were found in 15% to 30% of CRPC [castration-resistant prostate cancer] patients.”) (Fujita, p.290).
Fujita notes that certain mutations, including T878A, are present in the ligand binding domain (LBD). (Id.).
Fujita states that enzalutamide, among other compounds, has been used in patients with an AR mutation. (Id.).
Fujita states: “Anti-androgens such as bicalutamide and flutamide bind to the LBD of AR.” (Id., p.292).
Fujita states: “The COU-AA-301 trial showed that combination therapy of abiraterone acetate with prednisone significantly prolonged overall survival of patients with metastatic CRPC after chemotherapy by 3.7 months. The efficacy of enzalutamide and abiraterone was also confirmed in patients with metastatic CRPC before chemotherapy.” (Id.).
Fujita states darolutamide can inhibit AR transcriptional activity with point mutations F877L, H875Y/T878A, F877L/T878A, and T878G. (Id.).
Fujita states darolutamide is being studied for men expressing metastatic CRPC. (Id.).
Fujita states: “All of these AR-targeted therapies target the LBD.” (Id.).
Ascertaining the differences between the prior art and the claims at issue
Cote does not disclose a combination therapy with Example 17 and an ARSI, such as enzalutamide. Scher, Luo, and Raymon are relied on for that claim element.
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant application reports a phase 2 clinical study using Example 17 and enzalutamide. Of the subjects treated, 9.4% had pathogenic mutations L702H, 12.5% had pathogenic mutations T878A, and 9.4% had pathogenic mutations H875Y. (Spec., ¶38). The application refers to the data in FIG. 3 and asserts a synergistic effect from co-administration of Example 17 and enzalutamide. (Id., ¶43).
The question of obviousness
Based on the above factors, it would have been prima facie obvious for a person having ordinary skill in the art prior to the filing of the instant application to combine the teachings of Cote, Scher, Luo, Raymon, and Fujita to arrive at the claimed method of treating “prostate cancer [that] comprises at least one pathogenic androgen receptor mutation” with a pharmaceutical composition comprising Example 17 and enzalutamide because Cote discloses Example 17 as a chemotherapeutic agent while Scher, Luo, and Raymon disclose using enzalutamide in combination with a chemotherapeutic agent to treat patients having castration-resistant prostate cancer, and Fujita teaches that 15–30% of patients with CRPC have an AR mutation.
One of ordinary skill in the art would have been motivated to modify Cote for combination therapy because Cote acknowledges the potential of a combination therapy, Scher suggests using enzalutamide in combination therapy for prostate cancer due to “the central role of the androgen receptor and androgen-receptor signaling in the progression of prostate cancer throughout the spectrum of disease,” and Luo and Raymon illustrate combination therapies for treating prostate cancer with small molecules and enzalutamide has been established at the time of invention. Thus, there would have been a reasonable expectation of success at arriving at the claimed invention because the level of ordinary skill in the art is high and combination therapies are useful for patients having drug resistance in the context of prostate cancer.
The evidence in the Specification has been considered but it is not commensurate in scope with any of the claims. The examples in the Specification utilize a combination of Example 17 and enzalutamide to treat subjects with pathogenic mutations L702H, T878A, and H875Y; however, those elements are not provided in a claim.
Reply to Arguments
Applicant argues a prima facie case of obviousness has not been established because the Office Action failed to address the language in the claim 1 preamble directed to “prostate cancer [that] comprises at least one pathogenic androgen receptor mutation.” (Remarks, p.5).
The rejection above has been amended to account for the claim preamble.
Applicant next argues the teachings of the cited references would not have provided a reasonable expectation of success because certain compounds discussed in the reference are not structurally related to the claimed compound. (Id., pp.5–6). This argument is not persuasive. Absolute predictability is not required. A reasonable expectation of success in combining the teachings of the cited references to arrive at the claimed method exists because the claimed compound is disclosed in Cote as being useful for treating prostate cancer and Luo, Raymon, and Fujita disclose the use of enzalutamide in combination with another agent for the treatment of prostate cancer.
Double Patenting
(i) Claims 1–7 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1–4, 14–20, 24, and 25 of U.S. Pat. App. No. 17/628,948 (reference claims) in view of Scher, Luo, Raymon, and Fujita.
Both the instant claims and the reference claims are directed to a method of treating cancer comprising administering the same compound in combination with an ARSI.
The same ARSI compounds (bicalutamide, enzalutamide, apalutamide, flutamide, nilutamide, darolutamide, and abiraterone acetate) are recited in dependent claims of each application.
The instant claims are directed to prostate cancer comprising at least one pathogenic androgen receptor mutation, whereas the reference claims are silent with respect to such mutations.
The discussion of Scher, Luo, Raymon, and Fujita above is incorporated herein by reference. The reference claims discloses the compound in the instant claims as a chemotherapeutic agent while Scher, Luo, and Raymon disclose using ARSI enzalutamide in combination with a chemotherapeutic agent to treat patients having castration-resistant prostate cancer, and Fujita teaches that 15–30% of patients with CRPC have an AR mutation.
One of ordinary skill in the art would have been motivated to modify the reference claims in view of Scher, Luo, Raymon, and Fujita because the reference claims are directed to a combination therapy, Scher suggests using enzalutamide in combination therapy for prostate cancer due to “the central role of the androgen receptor and androgen-receptor signaling in the progression of prostate cancer throughout the spectrum of disease,” and Luo and Raymon illustrate combination therapies for treating prostate cancer with small molecules and enzalutamide has been established at the time of invention. Thus, there would have been a reasonable expectation of success at arriving at the claimed invention because the level of ordinary skill in the art is high and combination therapies are useful for patients having drug resistance in the context of prostate cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reply to Arguments
Applicant argues the rejection based on U.S. Pat. App. No. 17/628,948 was not based on a proper obviousness analysis. (Remarks, p.6). The rejection has been modified to include an obviousness analysis.
Conclusion
No claims are allowed.
Communication
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/JASON M. NOLAN/Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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