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 .
Priority
This application, filed on 03/11/2021, claims priority to U.S. Provisional Applications No. 62/730,869 filed on 09/13/2018, 62/737,612 filed on 09/27/2018 and 62/778,185 filed on 12/11/2018, and international application PCT/US2019/050970 filed on 09/13/2019.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 08/24/2022, 11/09/2023, 04/25/2024, 09/12/2024, 12/06/2024, and 10/20/2025, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
DETAILED ACTION
The Amendments and Applicant’s Arguments submitted on 05/20/2026 have been received and
have been carefully considered.
Claims 1 and 11-13 were amended, claims 14-17 were cancelled, claims 4-8 were previously cancelled, and claims 22-23 were added. Claims 1-3, 9-13 and 18-23 are pending, claims 3 and 20-22 are currently withdrawn, and claims 1-2, 9-13, 18-19 and 23 are under consideration.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim 18 recites “the method according to claim 1, wherein the subject has a spike in PSA either at 4 weeks or 8 weeks of treatment.” The instant specification defined the “spike in PSA” as:
“The term "disease progression" as used herein refers to an increase in prostate specific antigen ("PSA") and/or progressing metastatic disease.” [Specification, pg. 14, 0056]. “The subject has metastatic disease with rising PSA”, [Specification, pg. 19, 0082].
As such, spike in PSA is associated with disease progression, and rising PSA indicates disease progression. Therefore, “spike in PSA” will be interpreted consistent with the instant specification.
Note: Applicant argues at page 1 of the Remarks filed on 10/20/2025, “Applicant's specification describes a "spike" in prostate specific antigen (PSA) to include an increase and subsequent decrease in PSA levels. For example, Applicant's specification defines a spike in PSA at four weeks of treatment as an increase in PSA at four weeks of treatment (relative to baseline levels at week 0), followed by a decrease in PSA from week 4 to week 8 of treatment. Specification at [0099].
Withdrawn Claim Rejections - 35 USC § 102
Rejection of claim 1-2, 9-16, and 18-19 under 35 U.S.C. 102(a)(1) as being anticipated by Pantuck, A.J., et al. (29 August 2018), Adv. Therap., 1: 1800104, is withdrawn in view of Applicant amendment filed on 05/20/2026 that amended claim 1 with “wherein the BET inhibitor is administered at a daily dose of 60 mg, 72 mg, 96 mg, or 120 mg.”
Response to Arguments:
Applicant argues:
Without acquiescing to any rejection and solely to advance prosecution, Applicant has amended claim 1 to recite an additional second therapeutic agent, specific daily doses of the BET inhibitor, and that the claimed method does not result in thrombocytopenia as a dose-limiting toxicity.
Examiner response:
Applicant’s arguments have been considered but are moot because instant claims are now rejected under 35 U.S.C. 103 as being unpatentable over Pantuck and Quinn. See the 103 Rejection below.
Withdrawn Claim Rejections - 35 USC § 103
Rejection of claim 17 under 35 U.S.C. 103 as being unpatentable over Pantuck, A.J., et al. (29 August 2018), Adv. Therap., 1: 1800104) in view of Z. Wang et al. Mol Med Rep. 2017 Oct;16(4):5450-5458), is withdrawn in view of Applicant amendment filed on 05/20/2026 that cancelled claim 17.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 9-13, 18-19 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Pantuck, A.J., et al. (29 August 2018), Adv. Therap., 1: 1800104, “Pantuck” cited in the IDS dated 11/09/2023) in view of J. Quinn et al. (US PG PUB 2017/0216301A1, 08/03/2017, “Quinn”, cited in PTO-892 dated 06/13/2024).
Note: This application currently names joint inventors (S. Lakhotia is a co-inventor in the instant Application). 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.
Pantuck teaches using CURATE.AI, an artificial intelligence platform for a method of administrating a combination of bromodomain inhibitor (ZEN-3694) and enzalutamide to a patient with metastatic castration-resistant prostate cancer to reduce serum prostate-specific antigen (PSA) levels, wherein, CURATE.AI successfully identifies substantial ZEN-3694 and enzalutamide dose adjustments, increasing both treatment efficacy and tolerance, stops disease progression, control PSA levels and reduced lesion size. [Abstract].
ZEN-3694 has the structure below, which the same claimed compound of claim 1:
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Pantuck teaches the co-administration of 48 mg ZEN-3694 and 160 mg enzalutamide once daily per study, [page 2, col. 2, last para.].
Pantuck’s study construct an individualized CURATE.AI profile that represented the calibration of a patient’s unique relationship between varied drug dose and efficacy, [page 3, col. 1 last para.]. CURATE.AI directly correlates the drug-dose inputs to the efficacy/toxicity outputs, and is disease mechanism–independent and indication-agnostic. [page 2, col. 1, 1st para.]. The dose adjustments were used to construct a CURATE.AI profile, which directly correlates drug dosing with treatment efficacy and is represented by a smooth surface that is unique to each patient. This profile also changes dynamically as drug synergy is time-dependent, dose-dependent, and patient-specific. Importantly, this surface implicitly incorporates the patient’s disease heterogeneity (e.g., Trans-omics and patient physiological functions), and only the patient’s own data are used to create a prospective treatment regimen. [page 6, col. 2 1st para.].
With regard to claim 1 amendment “wherein administering the BET inhibitor and the second therapeutic agent does not result in thrombocytopenia as a dose-limiting toxicity”, Pantuck discloses that the patient under the combination therapy of ZEN-3694 and enzalutamide reported safety, tolerance, and no adverse effect. [Pg. 3, col. 2, last para.]. Pantuck discloses that the dose adjustment of the drugs shows safety and tolerability. [Pg. 3].
While Pantuck teaches a personalized does adjustment to a patient with metastatic prostate Cancer, Pantuck does not teach the claimed daily dose of 60 mg, 72 mg, 96 mg, or 120 mg.
Quinn teaches bromodomain inhibitors of Formula Ia for treatment of cancer, Quinn, pg. 6, 0027], wherein cancer is prostate cancer. [Quinn, pg. 9, 0057]. Quinn teaches the claimed compound I as species of Formula Ia, compound 146:
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[Quinn, pg. 117, Comp. 146, last comp.].
Quinn teaches that BET inhibitor compounds of Formula I can be used to treat cancer that have an overexpression, translocation, amplification, or rearrangement c-myc or other myc family oncoproteins (MYCN, L-myc) i.e., prostate cancer, are particularly sensitive to BET inhibition. [Quinn, pg. 35, 0481]. Quinn tested the BET bromodomains inhibition activity of the Species of Formula 1, wherein compound 146 deemed highly active in inhibiting cell proliferation in cancer cell lines [Quinn, pg. 139, 0946, 0949, Table 3, 5 comp. 146]. Quinn teaches that because of potential synergy or additive effects between BET inhibitors and other cancer therapy, the BET inhibitor i.e., comp. 146 can be combined with other therapies, chemotherapeutic agents, or anti-proliferative agents to treat human cancer and other proliferative disorders. [Quinn, pg. 36, 0486]. Quinn teaches that preliminary doses are determined according to animal tests, and the scaling of dosages for human administration is performed according to art-accepted practices. Quinn teaches that toxicity and therapeutic efficacy are determined by standard pharmaceutical procedures, and the dose ratio between toxic and therapeutic effects is the therapeutic index, the large therapeutic indices are preferable. Quinn teaches that the dosage of the compounds lies within concentrations with little or no toxicity, and the dosage may vary depending upon the Subjects age, condition, and gender, the route of administration as well as the severity of the medical condition in the Subject, and it’s determined by a physician and adjusted, as necessary, to suit observed effects of the treatment. [Quinn, pg. 38, 0501-0504]. Quinn teaches that 2.5 to 45 mg/kg and 30 mg/kg of BET compounds [0971]. Quinn’s amounts calculate to 12.1 mg -218.9 mg when the dose of BET compounds is translates from mice to human.1
In view of the teachings of Pantuck and Quinn, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of instantly claimed invention to administer Pantuck at a daily dose of 12.1-218.9 mg, for example 60 mg, 72 mg, 96 mg, or 120 mg. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Pantuck teaches
a method for treating a prostate cancer by administering BET inhibitor, ZEN-3694 and enzalutamide, and teaches a method of creating treatment regimen and individualized the dose of ZEN-3694 and enzalutamide based on patient’s own data and profile that represented the calibration of a patient’s unique relationship between varied drug dose and efficacy/toxicity outputs, disease mechanism–independent and indication-agnostic, and the patient’s disease heterogeneity [page 2, col. 1, 1st para, page 3, col. 1 last para., page 6, col. 2 1st para.], and Quinn teaches that doses are vary depending upon the Subjects age, condition, and gender, the route of administration as well as the severity of the medical condition in the Subject, and it’s determined by a physician and adjusted, as necessary, to suit observed effects of the treatment. [Quinn, pg. 38, 0501-0504]. The dose of 12.1-218.9 mg of ZEN 3694 overlapped and encompassed the claimed doses, and as provided in MPEP 2144.05 “in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005).” Furthermore, MPEP 2144.05.II.A explains: “generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).” Therefore, Pantuck and Quinn meet each and every limitation of claims 1.
Claim 2 is met because Pantuck discloses Compound 1.
Claim 9 is met because Pantuck discloses that the patient has metastatic castration-resistant prostate cancer.
Claims 10, 11, and 12 are met because Pantuck discloses that the patient has prior prostate-specific antigen (PSA) level progression on abiraterone. [Pg. 8, col. 1, last para.].
Claim 13 is anticipated because Pantuck discloses that the patient is enzalutamide naïve. [Pg. 8, col. 1, last para.].
Claim 18 is met because Pantuck discloses that the patient has PSA level progression thought weeks 0-5 of the combination therapy, wherein after optimum ZEN-3694 and enzalutamide doses, the patient’s PSA level was observed to decrease from 14.3 to 4.8 ng mL−1, followed by decrease in PSA level from 4.8 to 2.4 ng mL−1 at weeks 6 to 7 of combination therapy. [Pg. 3, col. 1st 2nd para.].
Claim 19 is met because Pantuck discloses that the combination is ZEN-3694 with enzalutamide.
Claim 23 is met because Pantuck’s patient has not been treated with taxane chemotherapy.
Conclusion
Claims 1-2, 9-13, 18-19 and 23 are rejected. No claim is allowed.
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 CFR 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 CFR 1.17(a)) pursuant to 37 CFR 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.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/
Supervisory Patent Examiner, Art Unit 1622
1 See Dose translation from animal to human: Reagan-Shaw et al. The FASEB Journal, March 2007, Vol. 22, page 659-661. 2.5 mg/kg x 3 (mine Km factor)/37 (human Km factor) = 0.203 mg/kg x 60 kg (human average weight) = 12.1 mg
45 mg/kg x 3 (mine Km factor)/37 (human Km factor) = 3.649 mg/kg x 60 kg (human average weight) = 218.9 mg
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