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 10/20/2025 have been received and
its contents have been carefully considered.
Claims 1-3, 10, 12, and 14-18 were amended, claims 6-8 were canceled, claims 4 and 5 were previously cancelled, and claims 19-21 were added. Claims 1-3 and 9-21 are pending, claims 3, 20, and 21 are currently withdrawn, and claims 1-2 and 9-19 are under consideration.
Note: Claim 1 is amended by adding apalutamide, and abiraterone, however, Pursuant to the Election of Species Requirement, Applicant previously elected enzalutamide as species of androgen receptor antagonist. Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. See 37 CFR 1.142(b) and MPEP § 821.03.
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 § 103
Rejection of claims 1-2, 6, 9-16 and 18 under 35 U.S.C. 103 as being unpatentable over Philip Vitorino (US20180153867A1, 06/07/2018) in view of J. Quinn et al. (US20170216301A1, 08/03/2017), and rejection of claim 17 under 35 U.S.C. 103 as being unpatentable over Vitorino and Quinn in further view of Z. Wang et al. (Mol Med Rep. 2017 Oct;16(4):5450-5458), are withdrawn in view of Applicant persuasive argument that the claimed combination of BET inhibitor compound 1 and enzalutamide produced unexpected results. The reason for withdrawing the above rejections is discussed below:
The prior art of Vitorino does not provide in vivo studies. However, the instant specification provides Phase 2a study that evaluated a combination of Applicant’s Compound I and enzalutamide in subjects who were chemotherapy-naive and progressed on enzalutamide [00116] to [00118]. Applicant describes that the Phase 2a study demonstrated a continued radiographic Progression-Free Survival (rPFS) with an overall rPFS of 44.6 weeks compared to the expected 24-28 weeks for enzalutamide alone [Ex. 6, Fig. 7]. patients who previously progressed on enzalutamide experienced nearly double overall rPFS. Applicant also describes that patient who experienced a PSA response and PSA spike at week 4 or week 8 experienced longer median rPFS of >120 weeks (>27 months), compared to those who did not show a PSA spike or response [Ex. 6, Fig. 8]. The increase in ePFS to 44.6 weeks suggests that Compound I prolonged the progression of prostate cancer in patients, and it is significant and unexpected that those experienced a PSA spike at 4 weeks experienced such a significant increase in rPFS. [00117]). Also, discussed “that Compound I and enzalutamide induced an interferon-gamma response (activating immune system cancer-fighting properties) because several immune-related signature gene sets Were significantly up-regulated after eight weeks of Compound I [Ex. 10, Fig. 12A and 12B]. Moreover, Applicant demonstrated that the combination of Compound I with enzalutamide lacked thrombocytopenia as a dose-limiting toxicity, thus demonstrating an unexpected superior safety profile. [0012] and [0088]. These results provide support that the combination of the claimed compound and enzalutamide produced unexpected activity. Therefore, in view of the provided data, the combination of Vitorino and Quinn does not anticipate or render the instant claims obvious.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 9-16, and 18-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by
Pantuck, A.J., et al. (29 August 2018), Adv. Therap., 1: 1800104. “Pantuck” cited in the PTO-892).
Note: This application currently names joint inventors (S. Lakhotia is a co-inventor is 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, discloses 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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Therefore, Pantuck anticipates claim 1.
Claim 2 is anticipated because Pantuck discloses Compound 1.
Claim 9 is anticipated because Pantuck discloses that the patient has metastatic castration-resistant prostate cancer.
Claims 10, 11, 12, and 14 are anticipated 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.].
Claims 15 and 16 are anticipated because 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 the dose adjustment of the drugs to improve patient’s safety and tolerability. [Pg. 3].
Claim 18 is anticipated 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 anticipated because Pantuck discloses that the combination is ZEN-3694 with enzalutamide.
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.
Claim 17 is 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 PTO-892) in view of Z. Wang et al. Mol Med Rep. 2017 Oct;16(4):5450-5458, “Wang” cited in the PTO-892).
The disclosures set forth above in the 102 Rejection over the same Pantuck et al. reference is herein incorporated by reference.
While Pantuck discloses a method of treating castration-resistant prostate cancer comprising administering to a patient ZEN-3694 with enzalutamide, Pantuck does not specifically teach that the subject has an activation of the ETS transcription factor including TMPRSS2-ERG. However, Claim 17 is met by Pantuck in view of Wang, because according to Wang most of castration-resistant prostate cancer cases have TMPRSS2:ERG gene. Wang teaches that the TMPRSS2:ERG gene fusion is the most frequent genomic alteration in prostate cancer cases and results in overexpression of the transcription factor ERG, which is present in both early- and late-stage castration-resistant prostate cancer. [Wang, pg. 5451, col. 1, 1st para.].
Conclusion
Claims 1-2 and 9-19 are rejected. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MANAHIL MIRGHANI ALI ABDALHAMEED whose telephone number is (571)272-1242. The examiner can normally be reached M-F 7:30 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622