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 office action is in reply to Applicant’s Arguments/Remarks filed on 08/01/2025. This application 18/796,814, filed on 08/01/2022, is a 371 of PCT/JP2021/004083 filed on 02/04/2021 and claims priority to a foreign application JAPAN 2020-018099 filed on 02/05/2020.
Status of Claims
Claims 1, 6-8, 12 and 15-19 are cancelled. Claims 2-5, 9-11, 13-14 and 20 are amended. Claims 21-22 are new claims. Claims 2-5, 9-11, 13-14 and 20-22 are pending in the application. Claims 2-5, 9-11, 13-14 and 20-22 are rejected.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/03/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
WITHDRAWN REJECTIONS
The examiner withdraws rejections to claims 19 and 20 under 35 U.S.C. 112(b) because claim 19 is cancelled and claim 20 has been amended by the Applicant.
Additionally, the examiner withdraws rejections to claim 1 under 35 U.S.C. 101 because the claim was cancelled by the Applicant.
MAINTAINED AND/OR MODIFIED REJECTIONS
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 (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 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 2-5, 9-11, 13-14, and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over He et al. (US 2016/0324878 A1, Nov. 10, 2016) (hereinafter He) (IDS reference), in view of Kawahata et al. (WO 2018/097234 A1, May 05, 2018) (hereinafter Kawahata) (IDS reference) and Casara et al. (Oncotarget, Published Apr.13, 2018) (hereinafter Casara).
Regarding claims 2-5, 9-11, 13-14 and 20-22, He teaches a method for treating a cancer, comprising administering to a subject in need thereof a therapeutically effective amount of (i) a BTK inhibitor, (ii) an mTOR kinase inhibitor, and (iii) a Bcl-2 inhibitor or an IMiD (¶ [0007], pg.1). In some embodiments, the Bcl-2 inhibitor is selected from the group consisting of venetoclax (ABT-199), navitoclax, ABT-737, TW-37, sabutoclax, obatoclax, other known Bcl-2 inhibitors, and pharmaceutically acceptable salts thereof (¶ [0025], pg.3). He teaches that single targeted therapy (monotherapy) requires longer term treatment and often results in drug resistance and disease recurrence over time due to gene mutations in the target (e.g., cancerous) cells. Indeed, resistance to BTK inhibitor ibrutinib has been observed in patients (¶ [0078], pg.5). Combinations of drugs described herein are unexpectedly high synergistic or additive effects and can effectively overcome drug resistance and disease recurrence. Combination therapies described herein are much safer than monotherapy due to the lower doses used and can shorten treatment cycle because of better therapeutic effects and outcomes (¶ [0006], pg.1).
However, He does not explicitly teach a composition wherein the reversible BTK inhibitor is an oxoisoquinoline derivative of the formula (I), (Ia), or (I-A). Furthermore, He does not teach that said BCL-2 inhibitor is S-55746.
Kawahata discloses a BTK inhibitor used in treating cancer (¶ [0029]).
PNG
media_image1.png
154
242
media_image1.png
Greyscale
in example 23 (¶ [0094]). This compound meets the formula of the BTK inhibitor in claims 2-4 wherein:
R1 is an hydroxymethyl group,
R2 is hydrogen, Q is
PNG
media_image2.png
128
114
media_image2.png
Greyscale
,
R3 is a substituted heterocyclic group, and
R3a is a substituted tetrahydropyridyl group.
The disclosed compound also meets the compound used as a BTK inhibitor in claims 5 and 13-14.
Additionally, Casara teaches a novel orally bioavailable BCL-2 selective and potent inhibitor called S55746 (also known as BCL201) that impairs hematological tumor growth (abstract).
As discussed above, He provides several advantages of combination therapy over using BTK inhibitor alone in the treatment of cancer. It would have been obvious to one of ordinary skill in the art, before the effective filing date, to combine any of the BTK inhibitors in instant claim 2-5 with the BCL-2 inhibitors in instant claims 13-14 to treat cancer. One would have been motivated to do so because He teaches that combination therapy provides better overall patient outcomes versus monotherapy. Additionally, “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from there having been individually taught in the prior art." See MPEP 2144.06(I).
Response to Arguments
The Remarks of August 1, 2025 have been fully considered but are not fully persuasive for the reasons below.
Applicant’s Argument:
Applicant argues in substance that He in view of Kawahata-1 and Casara do not teach the invention as a whole because the combination of fails to teach the pharmaceutical composition of amended claim 2 comprising the reversible BTK inhibitor and BCL-2 inhibitor.
In response to applicant’s argument, the examiner acknowledges applicant’s remarks, however, respectfully disagrees as they are not in commensurate with the scope of the claims with respect to the composition. Examiner notes that He was utilized to teach a BCL-2 inhibitor (see 0007). Kawahata specifically discloses the reversible BTK inhibitor required by applicant (i.e., trizaine). In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, combinations of drugs described herein are unexpectedly high synergistic or additive effects and can effectively overcome drug resistance and disease recurrence. Combination therapies described herein are much safer than monotherapy due to the lower doses used and can shorten treatment cycle because of better therapeutic effects and outcomes (see He [0006], pg.1).
Conclusion
No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHAR INAM whose telephone number is (571)272-0821. The examiner can normally be reached 7:30 am-5:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SAHAR INAM/
Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
Prosecution Insights