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 .
Status of Claims
Pursuant to the amendment, filed on May 5, 2025, claims 1-97 are canceled. Claims 98-117 are new with claims 98, 114, 115, and 117 being the independent claims.
Claims 98-117 are pending in the application
Priority
This application, filed on August 29, 2024, is a National Stage entry from International Application No. PCT/US2023/013116, filed on February 15, 2023, which claims benefit under 35 U.S.C. 119 or 365 to U.S. Provisional Application Nos. 63/315,240, filed Mar. 1, 2022, and
63/425,839, filed Nov. 16, 2022.
Information Disclosure Statement
The information disclosure statements (IDSs), filed on August 29, 2024 and May 5, 2025, have been acknowledged and considered.
Claim Rejections - 35 USC § 112(a)
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.
Claims 98-113 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.
Further, 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.
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 disease or disorder in a human subject in need thereof, wherein the disease or disorder is sex hormone-dependent or androgen receptor driven, the method comprising intramuscularly administering to the human subject a therapeutically effective amount of a pharmaceutical composition once every 1-3 months, wherein the pharmaceutical composition comprises abiraterone decanoate in its basic form and a pharmaceutically acceptable carrier, wherein each administration of the pharmaceutical composition comprises administering to the human subject 50 mg to 2000 mg of abiraterone decanoate:
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wherein the method selectively inhibits CYP17A1 lyase activity over CYP17A1 hydroxylase activity in the human subject.
The phrase “wherein the method selectively inhibits CYP17A1 lyase activity over CYP17A1 hydroxylase activity in the human subject” is contrary to the lack of selectively of abiraterone for those activities expressed in the specification, which states both are inhibited by abiraterone. (Spec., ¶[0003]) (“Abiraterone potently and selectively inhibits both CYP17A1 17α-hydroxylase and 17,20-lyase enzyme activities, hereinafter may be simply referred to as CYP17A1 hydroxylase activity and CYP17A1 lyase activity”). The specification does not show the claimed prodrug administered intramuscularly has the claimed selectivity. Accordingly, the wherein phrase in claim 98 is in conflict with the description.
Additionally, examples of the method in the specification involve the coadministration of abiraterone decanoate with glucocorticoids, namely prednisone and dexamethasone (Spec., ¶[0306]). The Specification does not provide any examples of administering the prodrug alone. There are no examples in the specification showing monotherapy administration of abiraterone decanoate, i.e., without a glucocorticoid. The examples and figures only show coadministration with a glucocorticoid, namely prednisone and dexamethasone (Spec., ¶¶ [0027], [0291]-[0292], [0297], and [0299]). It is noted the specification states, in some embodiments, a glucocorticoid replacement therapy is not required (¶[0224]), however all the methods exemplified in the specification show coadministration of dexamethasone with abiraterone decanoate. For example, the specification states administration of abiraterone decanoate intramuscularly to human subjects achieved lyase selectivity, and references FIG. 3E which shows progesterone levels return to baseline as a result of the administration. However, Cohort 5 also received 0.5 mg of dexamethasone once daily (¶[0027]) and therefore assumes abiraterone decanoate alone attributes to the decrease in progesterone (¶[0056]).
(B) The extent and content of the prior art: according to a review article (Bird et al., Journal of Steroid Biochemistry & Molecular Biology 163 (2016) 136–146), abiraterone is well known to be selective for the CYP17A1 enzyme, and has been represented as a substantial advance in available therapy for prostate cancer. According to Bird et al., while abiraterone is a substantial advance in therapy, declines in cortisol and elevation of deoxycorticosterone and corticosterone as a result of abiraterone administration, confirm the site of action is clearly more at the level of the hydroxylase activity of CYP17A1; increases in pregnenolone and progesterone further supported that abiraterone inhibits the hydroxylase activity. Bird et al., further states that glucocorticoid replacement therapy can also lower the accumulation of pregnenolone and progesterone, which aids in hypertension, but adds further complications associated with long term glucocorticoid therapy (p. 143, 3.2 First generation CYP17 inhibitors without 17,20 lyase selectivity). Abiraterone decanoate is recited to be a prodrug of abiraterone in the claimed invention (Spec., ¶[0002]; Title) and according to the Specification: “The prodrugs described herein include those compounds that readily undergo chemical changes under physiological conditions to provide active abiraterone.” (Spec., ¶[0263]).
Seviteronel (VT-464), a novel, nonsteroidal, small molecule CYP17A1 inhibitor with lyase selectivity was tested for anticancer activity in comparison to abiraterone (Toren et al., Mol Cancer Ther (2015) 14 (1): 59–69) (p. 59, Abstract). Toren et al. teaches that abiraterone acetate (acetylated prodrug of abiraterone) specifically and irreversibly inhibits both CYP17 hydroxylase and lyase, and inhibition of the hydroxylase leads to mineralocorticoid excess, which can be partially suppressed by coadministration of prednisone. Toren et al. further states: “The development of selective CYP17A1 lyase inhibitors has potential to obviate the need for concomitant prednisone administration in patients which is associated with its own toxicities.” (p. 59, Introduction). In clinical trials (NCT02130700 and NCT02012920), VT-464 is dosed without the need of prednisone in phase II trials with patients who have failed enzalutamide, abiraterone, or chemotherapy (Id., p. 68, Discussion).
Accordingly, while the prior art does describe a compound, like VT-464, can achieve CYP17A1 lyase selectivity, the need for glucocorticoid therapy should be obviated. Based on the teachings of the prior art, abiraterone acetate and abiraterone show inhibition of both CYP17A1 hydroxylase and lyase activity, and that a prodrug is just an inactive form of the active drug. In other words, the teachings suggest that abiraterone decanoate when administered to a subject and metabolized, will behave the same way as abiraterone.
(C) The maturity of the science or technology: while compounds do exist for selective inhibition of the lyase activity over hydroxylase of CYP17A1, abiraterone, in view of the prior art, is considered to inhibit both hydroxylase and lyase activity. The prior art discusses that VT-464 achieves lyase selectivity and is currently in clinical trials as an intervention without the need for glucocorticoids to decrease the buildup of pregnenolone and progesterone. As such, the science relevant to the claimed invention is fairly mature in that abiraterone was a substantial advance in prostate cancer therapy, however more selective inhibitors for CYP17A1 lyase inhibition, like VT-464, are currently in clinical trials.
(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.
Conclusion regarding written description
When the above factors and evidence discussed therein are considered as a whole, the specification (in view of the prior art) does not adequately describe a method in which abiraterone decanoate is selective for the lyase over the hydroxylase activity of CYP17A1, or administering abiraterone without also taking prednisone and dexamethasone to lower build-up of progesterone. Accordingly, the Specification does not reasonably convey to those skilled in the art the Applicant had possession of the claimed subject matter as of the filing date.
Examiner recommends removing the limitation “…wherein the method selectively inhibits CYPl7Al lyase activity over CYPl7Al hydroxylase activity in the human subject.” in claim 98. Claims 99-113 do not rectify the written description issue of claim 98 and are therefore rejected by virtue of their dependency.
Claim Rejections - 35 USC § 112(b)
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 112 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.
The phrase "such as" appears in the (C) and (D) alternatives of the claimed method, which 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 § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 98, 100-102, 104-105, and 115-117 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Open-label, Multicenter Study of Intramuscular PRL-02 Depot in Patients With Advanced Prostate Cancer, Identifier: NCT04729114, first posted January 28, 2021, last updated February 2, 2021, accessed July, 29, 2026 (“NCT04729114”) evidenced by Metastatic castration-resistant prostate cancer (mCRPC), Mayo Clinic, (December 24 2025, Accessed July 30, 2026), https://www.mayoclinic.org/diseases-conditions/metastatic-castration-resistant-prostate-cancer/symptoms-causes/syc-20593191 (“Mayo”).
Claim 98 recites a method of treating a disease or disorder in a human subject in need thereof, wherein the disease or disorder is sex hormone-dependent or androgen receptor driven,
the method comprising intramuscularly administering to the human subject a therapeutically effective amount of a pharmaceutical composition once every 1-3 months, wherein the pharmaceutical composition comprises abiraterone decanoate in its basic form and a pharmaceutically acceptable carrier, wherein each administration of the pharmaceutical composition comprises administering to the human subject 50 mg to 2000 mg of abiraterone decanoate:
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wherein the method selectively inhibits CYP17A1 lyase activity over CYP17A1 hydroxylase activity in the human subject. Claim 100 recites wherein the disease or disorder is selected from endometrial cancer, endometriosis, ovarian cancer or prostate cancer. Claim 101 recites wherein the disease or disorder is a cancer, wherein the cancer is prostate cancer. Claim 104 recites wherein the human subject has a measurable prostate specific antigen or a localized prostate cancer. Claim 105 recites wherein the cancer is a metastatic castration sensitive prostate cancer (mCSPC), non-metastatic castration-sensitive prostate cancer, nonmetastatic castration-resistant prostate cancer, or metastatic castration-resistant prostate cancer (mCRPC).
NCT04729114 teaches administration of PRL-02 (abiraterone decanoate) for intramuscular injection at 4 different doses for 4 different cohorts every 84 days: patients in Cohort 1 received 180 mg of PRL-02, Cohorts 2,3, and 4 received 360 mg, 720 mg, 1260 mg, respectively, of the same (pp. 8-10, Arms and Interventions). The patient population eligible to receive PRL-02 have documented metastatic castration-sensitive prostate cancer, metastatic castration-resistant prostate cancer, or biochemical relapse of prostate cancer through prostate specific antigen progression defined by the Prostate Cancer Working Group (p. 11, Eligibility, Criteria). The primary outcome measures include testosterone suppression over the course of treatment (p. 10, Outcome Measures).
The recitation of “…wherein the method selectively inhibits CYPl7Al lyase activity over CYPl7Al hydroxylase activity in the human subject” in instant claim 98 and the recitation of “…wherein the pharmaceutical composition is administered in an effective amount to achieve a sustained reduction of serum testosterone level in the human subject to 50% below baseline [levels of progesterone as a result of administration]…” in instant claim 117, are intended results of the method steps recited and are not given weight as limitations (MPEP §2111.04). Furthermore, the same therapy is administered in NCT04729114 and therefore the intended results would be considered inherent upon administration of the same abiraterone decanoate prodrug (MPEP §2112(III)). Accordingly claims 98, 100-101, 104-105, 107, and 117 are anticipated by NCT04729114.
Mayo states: “Metastatic prostate cancer happens when cells break away from the cancer in the prostate and spread to other parts of the body. If the cancer no longer responds to hormone therapy, then it's considered metastatic castration-resistant prostate cancer. Prostate cancer cells can spread through the blood or through the lymphatic system. When prostate cancer spreads, it most often goes to: 1) Lymph nodes, 2) Bones, 3) Liver, and 4) Lungs.” (p. 4).
Based on the teachings of NCT04729114 and the evidence provided by Mayo with respect to metastatic prostate cancers spreading to the lymph nodes, claims 102 and 115-116 are anticipated by NCT04729114.
Claim Rejections - 35 USC § 103
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 99, 108, and 111 are rejected under 35 U.S.C. 103 as being unpatentable over NCT04729114 in view of Study to Evaluate Exicorilant (CORT125281) in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer, Identifier:NCT03437941, first posted February 19, 2018, last updated December 9, 2020, accessed July 29, 2026 (“NCT03437941”), further in view of Bird et al., Journal of Steroid Biochemistry & Molecular Biology 163 (2016) 136–146 (“Bird”).
NCT04729114 teaches administration of PRL-02 (abiraterone decanoate) for intramuscular injection at 4 different doses for 4 different cohorts every 84 days: patients in Cohort 1 received 180 mg of PRL-02, Cohorts 2,3, and 4 received 360 mg, 720 mg, 1260 mg, respectively, of the same (pp. 8-10, Arms and Interventions). The patient population eligible to receive PRL-02 have documented metastatic castration-sensitive prostate cancer, metastatic castration-resistant prostate cancer, or biochemical relapse of prostate cancer through prostate specific antigen progression defined by the Prostate Cancer Working Group (p. 11, Eligibility, Criteria).
NCT04729114 does not teach administering abiraterone decanoate to patient populations with human subjects suffering from side effects due to hydroxylase inhibition, with human subjects who progressed on or after androgen receptor antagonist-based treatments, or further administration of enzalutamide.
NCT03437941 teaches oral administration of CORT125281 in combination with enzalutamide to patients with metastatic castration-resistant prostate cancer. Once the dosing regimen was determined, expanded cohorts were 1) patients who have progressed during treatment with abiraterone and have received no other androgen receptor (AR)-blocking therapies, and 2) patients who have progressed during treatment with enzalutamide or other second-generation AR inhibitors (pp. 6-7, Study Description).
NCT03437941 does not teach abiraterone’s ability to inhibit hydroxylase activity of CYP17A1.
Bird teaches declines in cortisol and elevation of deoxycorticosterone and corticosterone as a result of abiraterone administration, confirmed the site of action is clearly more at the level of the hydroxylase activity of CYP17A1; increases in pregnenolone and progesterone further supported that abiraterone inhibits the hydroxylase activity (p. 143, 3.2 First generation CYP17 inhibitors without 17,20 lyase selectivity).
NCT04729114, NCT03437941, and Bird are analogous art to the claimed invention because they are in the same field of analyzing administration of therapies for better outcomes of prostate cancer. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) to combine the prior art elements to arrive at the method instantly claimed with reasonably predictable results. It would have been prima facie obvious to administer abiraterone decanoate at a dose of 180, 260, 720, or 1260 mg once every 84 days to patients with prostate cancer, based on the teachings of NCT04729114, and modify the patient population to include patients that progressed after receiving abiraterone and patients receiving androgen receptor antagonists, based on the teachings of NCT03437941, as both clinical trials are towards therapies for metastatic castration resistant prostate cancer (MPEP §2143(I)(A)). While NCT03437941 does not discuss hydroxylase inhibition side effects, it does discuss including patients who have received abiraterone, and based on the teachings of Bird, the mechanism of action of abiraterone is inhibition of hydroxylase activity which leads to declines in cortisol and increases in deoxycorticosterone, corticosterone, pregnenolone, and progesterone (vide supra). Accordingly, claims 99 and 108 are prima facie obvious.
Regarding claim 111, NCT03437941 teaches combination treatment of CORT125281 and enzalutamide to patients with mCRPC (vide supra). It would have been prima facie obvious to combine administration of abiraterone decanoate, as taught by NCT04729114, with enzalutamide, as taught by NCT03437941, because they are both known in the prior art as treatment for mCRPC (MPEP §2144.06(I)).
Claims 103, 106, and 112 are rejected under 35 U.S.C. 103 as being unpatentable over NCT04729114 in view of A Study of Abiraterone Acetate Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Participants With High-Risk, Metastatic Hormone-Naive Prostate Cancer (mHNPC), Identifier: NCT01715285, first posted October 26, 2012, last updated October 15, 2018, accessed July 29, 2026 (“NCT01715285”) and A Phase 2 Study to Evaluate Safety and Efficacy of Abiraterone Acetate in Male Participants With Prostate Cancer, Identifier: NCT00924469, first posted June 19, 2009, last updated April 17, 2013, accessed July 30, 2026 (“NCT00924469”).
The teachings of NCT04729114 are discussed above and are incorporated by reference herein.
Regarding claims 103, 106, and 112, NCT04729114 does not teach administering therapy to patients with a Gleason score ≤ 6, with newly diagnosed high risk metastatic hormone sensitive prostate cancer, and patients that are hormone therapy naïve prior to administration of a therapy.
NCT01715285 teaches a study to determine if newly diagnosed (within previous 3 months) participants with metastatic (spread of cancer cells from one part of the body to another) hormone-naïve prostate cancer (mHNPC) who have high-risk prognostic factors will benefit from the addition of abiraterone acetate and low-dose prednisone to androgen deprivation therapy (p. 12, Study Description).
NCT01715285 does not teach administering therapy to patients with a Gleason score ≤ 6.
NCT00924469 teaches a study to evaluate the safety and efficacy of abiraterone acetate plus leuprolide acetate and prednisone, versus leuprolide acetate alone in male participants with prostate cancer who are suitable candidates for prostatectomy (surgery to remove all or part of the prostate gland) (p. 4, Brief Summary). The patients eligible to receive therapy were included if they had a Gleason score of 6 with either prostate specific antigen (PSA) ≥ 10ng/mL or PSA velocity ≥ 2 ng/mL/year (pp. 6-7, Eligibility Criteria).
NCT04729114, NCT01715285, and NCT00924469 are analogous art to the claimed invention because they are in the same field of administrating therapies for better outcomes of prostate cancer. Therefore, it would have been prima facie obvious to a PHOSITA to combine the prior art elements to arrive at the method instantly claimed with reasonably predictable results. It would have been prima facie obvious to administer abiraterone decanoate at a dose of 180, 260, 720, or 1260 mg once every 84 days to patients with prostate cancer, based on the teachings of NCT04729114, and modify the patient population to include patients that have high-risk prognostic factors and hormone-naïve prostate cancer, based on the teachings of NCT01715285, and further include patients that have a Gleason score of 6, based on the teachings of NCT00924469, as all clinical trials are towards therapies for prostate cancer (MPEP §2143(I)(A)).
Claims 110, 114, and 117 are rejected under 35 U.S.C. 103 as being unpatentable over NCT04729114 in view of US20200281945 (#1 in IDS filed August 29, 2024) (“Sharp”), further in view of US20150133416 (“Grenier”).
The teachings of NCT04729114 are discussed above and are incorporated by reference herein.
Regarding claims 110 and 114, NCT04729114 does not teach a pharmaceutical composition comprising abiraterone decanoate in its basic form in, in an amount of 100 mg to 300 mg; (b) benzyl alcohol in an amount of 50 mg to 150 mg; (c) benzyl benzoate in an amount of 100 mg to 300 mg; (d) com oil, q.s. to 1 milliliter; and/or 3-mercapto-1,2-propanediol in an amount of 0.5 mg to 20 mg.
Sharp teaches sustained release abiraterone prodrug formulations, to a subject having a sex hormone-dependent benign or malignant disorder such as prostate cancer (Abstract). Examples 3H and 3I show formulations of abiraterone decanoate (¶¶ [0350]-[0351] and [0354-[0355]). Example 3H comprises 209 mg/mL of abiraterone decanoate (2500 mg), wherein each milliliter (1 mL) of the solvent comprises 70% corn oil (PubChem SID: 481180756, density = 0.921 g/mL), 10% benzyl alcohol (PubChem CID: 244 , density = 1.042 g/mL), and 20% benzyl benzoate (PubChem CID: 2345, density = 1.1121 g/mL). Based on these teachings, the formulation contains 645 mg of corn oil (
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, 104 mg of benzyl alcohol (
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, and 222 mg of benzyl benzoate (
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. Sharp teaches preservatives can be a part of the formulation such as monothioglycerol, sucrose, etc. (¶ [0131]).
Sharp does not teach an amount of monothioglycerol in the formulation.
Grenier teaches pharmaceutical composition comprising abiraterone acetate (Abstract). The formulations can include other adjuvants that are antioxidants like ascorbic acid, monothioglycerol, etc., at an amount from 0.1% to 5% w/w (¶[0086]).
NCT04729114, Sharp, and Grenier are analogous art to the claimed invention because they are in the same field of formulating abiraterone prodrugs for administration. Therefore, it would have been prima facie obvious to a PHOSITA to combine the prior art elements to arrive at the method instantly claimed with reasonably predictable results. It would have been prima facie obvious to administer abiraterone decanoate at a dose of 180, 260, 720, or 1260 mg once every 84 days to patients with prostate cancer, based on the teachings of NCT04729114, wherein the formulation contained for each milliliter, 250 mg of abiraterone decanoate, 104 mg of benzyl alcohol, 222 mg of benzyl benzoate, and 645 mg of corn oil, based on the teachings of Sharp. Furthermore, based on Sharp, monothioglycerol could be added as a preservative in the formulation, but Sharp fails to teach an amount of the preservative. This is rectified by the teachings of Grenier which teaches formulations of abiraterone acetate can include an antioxidant like monothioglycerol at 0.1% to 5% w/w. Based on the teachings of Sharp, the total weight of the composition would be 1221 mg (summation of the aforementioned amounts of abiraterone decanoate, benzyl alcohol, benzyl benzoate, and corn oil) of which 0.1% w/w would lead a PHOSITA to include at least 1.22 mg of monothioglycerol.
Regarding claim 117, Sharp teaches reducing levels of androgens (e.g., testosterone) and/or estrogens by parenterally administering to a subject in need thereof an effective amount of abiraterone prodrug (¶[0018]). Fig. 14C shows sustained increase of progesterone level and reduction of glucocorticoid (cortisol) and sex hormone (testosterone) level (¶[0082]). The recitation of “…wherein the pharmaceutical composition is administered in an effective amount to achieve a sustained reduction of serum testosterone level in the human subject…” is an intended result and not given weight as limitations (MPEP §2111.04). Furthermore, the same drug was administered to suppress testosterone levels and therefore would be inherent upon administration (MPEP §2112(III)).
Claim 109 is rejected under 35 U.S.C. 103 as being unpatentable over NCT04729114 in view of RE-sensitizing With Supraphysiologic Testosterone to Overcome REsistance (The RESTORE Study) (Restore), Identifier: NCT02090114, first posted March 18, 2014, last updated May 14, 2020, accessed Jule 30, 2026 (“NCT02090114”).
The teachings of NCT04729114 are discussed above and are incorporated by reference herein.
Regarding claim 109, NCT04729114 does not teach administering therapy to a patient population that has developed resistance to the treatment of abiraterone acetate in combination with prednisone.
NCT02090114 teaches a study to determine the effects of parenteral testosterone followed by enzalutamide, abiraterone or castration-only therapy in men with metastatic CRPC who previously progressed on one of these forms of therapy (p. 6, Brief Summary). Patients eligible to receive parenteral testosterone therapy in combination with enzalutamide include Cohorts A and B, patients who have progressed on prior treatment with enzalutamide or abiraterone acetate + prednisone (by PSA criteria or radiographically), and patients who have histologically confirmed adenocarcinoma of the prostate (pp. 11-12, Criteria).
NCT04729114 and NCT02090114 are analogous art to the claimed invention because they are in the same field of administering therapy to patients suffering from prostate cancer. Therefore, it would have been prima facie obvious to a PHOSITA to combine the prior art elements to arrive at the method instantly claimed with reasonably predictable results. It would have been prima facie obvious to administer abiraterone decanoate at a dose of 180, 260, 720, or 1260 mg once every 84 days to patients with prostate cancer, based on the teachings of NCT04729114, and modify the patient population to include patients that progressed after receiving abiraterone acetate in combination with prednisone, based on the teachings of NCT02090114, as both clinical trials are towards therapies for mCRPC.
Claim 113 is rejected under 35 U.S.C. 103 as being unpatentable over NCT04729114 in view of Abiraterone Acetate Dose-Escalation Study in Hormone Refractory Prostate Cancer, Identifier: NCT00473746, first posted May 15, 2007, last updated April 14, 2014, accessed Jule 30, 2026 (“NCT00473746”).
The teachings of NCT04729114 are discussed above and are incorporated by reference herein.
Regarding claim 113, NCT04729114 does not teach administering 1260 mg of abiraterone decanoate intramuscularly once every three months and dexamethasone orally once daily at a daily dose of 0.5 mg/day.
NCT00473746 teaches a study that evaluated the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activities of abiraterone acetate in patients with hormone refractory prostate cancer (HRPC) (p. 6, Study Description). The study was conducted in 2 phases (Phase 1 and Phase 2). In the first part of the study (Phase 1), the maximum tolerated dose of abiraterone acetate was determined for use in the second part of the study (Phase 2). In Phase 2, prednisone or dexamethasone was administered concurrently with abiraterone acetate (p. 6, Detailed Description). The phase two dose treatment was a combination of abiraterone acetate and 0.5 mg of dexamethasone once daily (pp. 7-8, Arms and Interventions).
NCT04729114 and NCT00473746 are analogous art to the claimed invention because they are in the same field of administering therapy to patients suffering from prostate cancer. Therefore, it would have been prima facie obvious to a PHOSITA to combine the prior art elements to arrive at the method instantly claimed with reasonably predictable results. It would have been prima facie obvious to administer abiraterone decanoate at a dose of 1260 mg once every 84 days to patients with prostate cancer, based on the teachings of NCT04729114, and further administer the dexamethasone orally once daily at a dose of 0.5 mg, based on the teachings of NCT00473746, as both clinical trials are towards therapies for prostate cancer.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 98-117 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,792,292 (“ ‘292 ”). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 98-117 are obvious in view of claims 1-30 of ‘292.
Claim 6 of ‘292 recites abiraterone decanoate having the formula,
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, which is also a species of the genus of claim 1 of ‘292. Claim 12 recites a method of treating disorders selected from a sex hormone-dependent benign or malignant disorder, comprising administering to a subject a therapeutically effective amount of the composition of claim 5, which is a composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier. Claim 13 of ‘292 recites the method of administering is through injection via intramuscular, intradermal, etc. Claim 15 of ‘292 recites the disorder is selected from prostate cancer, ovarian cancer, etc. Claims 16-17 recite the disorder is a sex-hormone dependent benign or malignant disorder selected from castration resistant, castration sensitive, metastatic castration resistant, and metastatic castration sensitive, prostate cancer. Claims 19-20 recite further administration of a corticosteroid, selected from prednisone, prednisolone, and/or methyl prednisolone. Claim 23 of ‘292 recites a pharmaceutical composition comprising abiraterone decanoate having the same formula as claim 6, and a pharmaceutically acceptable oil and a pharmaceutically acceptable solvent wherein the amount of abiraterone decanoate is between 50 to 2000mg. Claim 26 recites a method of treating prostate cancer comprising administering to a subject in need thereof the pharmaceutical composition of claim 23 via intramuscular injection, intradermal injection, or subcutaneous injection, once a month or once in more than a month. Claim 27 recites the method comprises administering the composition of claim 23 via intramuscular injection.
Instant claims 98, 100-101, 105, 112, 115-116 are obvious in view of claims 6, 12,-13, 15-17, 19-20, 23, and 26-27 of ‘292 as the limitations are not patentably distinct.
Claims 98-117 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,957,696 (“ ‘696 ”). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 98-117 are obvious in view of claims 1-21 of ‘292.
Claim 1 of ‘696 recites a method of treating a sex hormone dependent or androgen receptor driven cancer in a non-castrated subject in need thereof, the method comprising parenterally administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an abiraterone prodrug, and further administering to the subject a bone protecting agent, wherein in the subject is characterized as having prostate cancer with bone metastasis. Claim 6 of ‘696 recites a method of administering a pharmaceutical composition comprising an abiraterone prodrug, wherein the abiraterone prodrug is abiraterone decanoate having the formula,
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. Claim 7 of ‘696 recites the pharmaceutical composition comprises for each milliliter, (a) abiraterone decanoate in its basic form, in an amount of about 100 mg to about 300 mg; (b) benzyl alcohol in an amount of about 50 mg to about 150 mg; (c) benzyl benzoate in an amount about 100 mg to about 300 mg; and (d) corn oil, q.s. to 1 milliliter. Claim 11 recites further administering to the subject one or more agents selected from hydrocortisone, prednisone, prednisolone, methylprednisolone, and dexamethasone. Claims 12 recites further administering to the subject a PARP inhibitor, a chemotherapeutic agent, etc. Claim 13 recites further administering to the subject niclosamide, an A2A receptor, etc. Claim 15 recites a method of administering a pharmaceutical composition comprising abiraterone decanoate wherein the subject is chemotherapy naïve or hormone therapy naïve prior to being administered the pharmaceutical composition. Claim 16 recites a method of administering a pharmaceutical composition comprising abiraterone decanoate wherein the reduction of serum testosterone level to about 50 ng/dL or below within 15 days of the first administration of the abiraterone prodrug. Claims 17-18 recite administration of the pharmaceutical composition administered via intramuscular injection, intradermal injection, etc., once a week or once in more than a week.
Instant claims 98, 100-101, 105, 112, 115-116 are obvious in view of claims 1, 6, 7, 11-13, and 15-18 of ‘696 as the limitations are not patentably distinct.
Claims 98-117 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 7, 9 , 12, 20, 27, 31, 45, 49, 54-55 of copending Application No. 17/635,106 (“ ‘106 ”). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 98-117 are obvious over claims 1-2, 5, 7, 9 , 12, 20, 27, 31, 45, 49, 54-55 of ‘106.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 of ‘106 recites a method of treating prostate cancer in a subject in need comprising intramuscularly administering to the subject once every 3 months a pharmaceutical composition comprising a therapeutically effective amount of abiraterone decanoate having the following formula, or a pharmaceutically acceptable salt thereof, dispersed or dissolved in a pharmaceutically acceptable carrier, wherein the abiraterone decanoate is characterized as having purity by weight of at least 95%,
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Claim 20 of ‘106 recites the method of claim 1 wherein (1) the subject is characterized as having a rising amount of PSA, (2) the prostate cancer is a localized prostate cancer; (3) the prostate cancer is a metastatic castration sensitive prostate cancer, non-metastatic castration-sensitive prostate cancer, non-metastatic castration-resistant prostate cancer, or metastatic castration-resistant prostate cancer; (4) the prostate cancer is a newly diagnosed high risk metastatic hormone sensitive prostate cancer; (5) the prostate cancer is a metastatic castration resistant prostate cancer (mCRPC), wherein the subject is asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated; (6) the prostate cancer is a metastatic castration resistant prostate cancer (mCRPC), wherein the subject's disease has progressed on or after a docetaxel-based chemotherapy regimen; or (7) the prostate cancer is a refractory prostate cancer. Claim 27 recites the method of claim 1 further comprising administering to the subject one or more agents selected from a chemotherapeutic drug, hormone replacement drug, or hormone ablation drug, etc. Claim 31 recites the method of claim 1 wherein the subject is administered one or more agents selected from prednisone, dexamethasone, PARP inhibitor, niclosamide, an A2A receptor antagonist etc. Claim 45 recites the method of claim 1 wherein the subject is chemotherapy naïve or hormone therapy naïve prior to being administered the pharmaceutical composition.
Instant claims 98, 100-101, 104-107, 112, 115-116 are obvious in view of claims 1, 6, 7, 11-13, and 15-18 of ‘106 as the limitations are not patentably distinct.
Claims 98-117 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-25 of copending Application No. 18/920,358 (“ ‘358 ”). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 98-117 are obvious over claims 3-25 of ‘358.
Claim 3 of ‘358 recites A method of treating prostate cancer in a subject in need thereof, the method comprising administering to the subject abiraterone decanoate via intramuscular injection, intradermal injection, or subcutaneous injection, once a week or once in more than a week, with each dose at about 50 mg to about 2000 mg of abiraterone decanoate, wherein the
abiraterone decanoate has the following formula,
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. Claims 4-6 recite the method comprises administering abiraterone decanoate intramuscularly at a dosing frequency ranging from once a month or once in more than a month, or once a week to once every three months. Claims 7-8 recite a method wherein the prostate cancer is castration resistant prostate cancer, castration sensitive prostate cancer, mCRPC, or mCSPC. Claims 9-12 recite a method of administering a composition, the composition comprising abiraterone decanoate, a pharmaceutically acceptable oil, and a pharmaceutically acceptable solvent, wherein abiraterone decanoate is in its basic form and present at a concentration of about 100 mg/mL to about 300 mg/mL, wherein the dosing frequency is once a week or once in more than a week with each dose at about 50 to 200mg of abiraterone decanoate. Claims 10-12 recite the pharmaceutically acceptable oil is corn oil, and the pharmaceutically acceptable solvents are benzyl alcohol and benzyl benzoate. Claim 18 recites administration of another compound selected from hydrocortisone, prednisone, prednisolone, methylprednisolone, and/or dexamethasone. Claim 25 recites a method of inhibiting CYP17A1 in a subject in need, the method comprising intramuscularly administering a pharmaceutical composition comprising abiraterone decanoate, a pharmaceutically acceptable oil, and a pharmaceutically acceptable solvent, wherein abiraterone decanoate is in its basic form and present at a concentration of about 100 mg/mL to about 300 mg/mL, wherein the dosing frequency is once a week or once in more than a week with each dose at about 50 to 200mg of abiraterone decanoate.
Instant claims 98, 100-101, 105, 107, 112, 115-116 are obvious in view of claims 3-25 of ‘358 as the limitations are not patentably distinct.
Conclusion
No claims are allowed.
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/SAHIL CHANDER AGGARWAL/Examiner, Art Unit 1623
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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