CTNF 18/717,529 CTNF 100562 DETAILED ACTION This office action is in response to applicant’s filing dated June 7, 2024. Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. 12-151 AIA 26-51 12-51 Status of claims Claims 1 - 15 are pending in the instant application. Acknowledgment is made of Applicant’s amendments filed June 7, 2024. Acknowledgment is made of Applicant’s cancelation of claims 16 - 37. Priority The present application is a 371 of PCT/US2022/052734, filed December 13, 2022 and claims the benefits of priority to the U.S. Provisional application No. 63/289,300, filed December 14, 2021. Information Disclosure Statement The information disclosure statements (IDS) submitted on June 7, 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. Drawings Acknowledgement is made of the drawings received on June 7, 2024. These drawings are accepted . Claim Objections 07-29-01 AIA Claim s 9 and 10 are objected to because of the following informalities: in line 1 claims recites “characterised”, which appears to be an orthographic error and should read “characterized” . Appropriate correction is required. Claim Rejections - 35 USC § 112 07-30-02 AIA 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. 07-34-01 Claim 15 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. 07-34-10 Regarding claim 15, the phrase "such as" in line 3 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 07-06 AIA 15-10-15 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. 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-15 AIA Claim s 1, 4, 6 – 8, 10 – 14 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Che et al ( Blood (2020) 136 (Supplement 1) : 33, cited in IDS, filed 06/07/2024, hereinafter Che) . Instant claims are drawn to a method of treating a refractory and/or relapsed mantle cell lymphoma in a patient in need thereof, comprising administering to the patient an effective amount of abemaciclib or a pharmaceutically acceptable salt thereof, in combination with an effective amount of a PI3K and/or a mTOR inhibitor, wherein the PI3K and/or mTOR inhibitor is Umbralisib, wherein the mantle cell lymphoma has acquired resistance to one or more BCL-2 inhibitors, such as resistance to venetoclax and ibrutinib, wherein mantle cell lymphoma is associated with t(11;14)(q13;q32) chromosomal translocation in CCND1 gene, cyclin D1 overexpression and wherein mantle cell lymphoma is retinoblastoma protein (Rb) proficient. Said method comprises further administering to the patient an effective amount of a BTK inhibitor. Che teaches combinational therapies to treat refractory and/or relapsed mantle cell lymphoma in patient, comprising administering abemaciclib in combination with other drugs, such as with PI3K inhibitor TGR-1202 (Umbralisib) or BTK inhibitor. Che conducted experiments on primary lymphoma cells from MCL patients as well as on ibrutinib-resistant or venetoclax-resistant MCL PDX models in vivo (page 1 – 2, “methods”). Che further teaches that, chromosomal translocation t(11:14)(q13:q32) of the cyclin D1 (CCND1) gene is the hallmark of MCL, which leads to overexpression of cyclin D1. Discussing experimental data, Che reports a significant inhibition of Rb1 phosphorylation by abemaciclib, in 4 different MCL cell lines (page 2, “results”). Thus, the presence of Rb1 protein in MCL cells indicates intact RB1 gene expression, confirming that these MCL cells are Rb-proficient. Thus, teachings of Che anticipate a method of claims 1, 4, 6 – 8 and 10 – 14 . Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-23-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim s 1 – 3, 5 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Che et al ( Blood (2020) 136 (Supplement 1) : 33, cited in IDS, filed 06/07/2024), in view of Stern et al (WO 2015/160986 A2, hereinafter Stern) . Instant claims are drawn to a method of treating mantle cell lymphoma in a patient in need thereof, comprising administering to the patient an effective amount of abemaciclib or a pharmaceutically acceptable salt thereof, in combination with an effective amount of a PI3K and/or a mTOR inhibitor, wherein the PI3K and/or mTOR inhibitor is a dual PI3K/mTOR inhibitor or pan PI3K inhibitor, such as copanlisib. The method comprises further administering to the patient an effective amount of one or more additional agent such as an aromatase inhibitor or a pharmaceutically acceptable salt thereof; AR inhibitors; CDK4/6 inhibitors; AKT inhibitors. Che teaches combinational therapies to treat mantle cell lymphoma in patient, comprising administering abemaciclib in combination with other drugs, such as with PI3K inhibitor. Che does not teach where PI3K inhibitor is a dual PI3K/mTOR inhibitor or pan PI3K inhibitor copanlisib. Che also does not teach where the method further comprises administering to the patient an effective amount of one or more additional agent such as an aromatase inhibitor or a pharmaceutically acceptable salt thereof; AR inhibitors; CDK4/6 inhibitors; AKT inhibitors. However, Stern teaches a method of treating a cancer, such as hematological cancer, e.g. mantle cell lymphoma (page 218, [00747]), comprising administering to the subject a PI3K inhibitor in combination with a CDK4/6 inhibitor (page 20, [0070]), wherein PI3K inhibitor is PF-05212384 (gedatolisib) or BAY 80-6946 (copanlisib) (page 11, [0031]) and CDK4/6 inhibitor is LY-2835219 (abemaciclib) (page 184, [00662]). Gedatolisib is a dual PI3K/mTOR inhibitor (Gedatolisib_Fact_Sheet_25MAY2018.pdf), and copanlisib is a pan PI3K inhibitor (Copanlisib | C23H28N8O4 | CID 135565596 – PubChem). Stern further teaches a method where the method includes further agents or therapies, such as chemotherapeutics agents selected from aromatase inhibiting 4(5)-imidazoles, anti-androgens (e.g. flutamide and bicalutamide) or EGFR inhibitors (erlotinib, gefitinib) (pages 211 – 213, [00738]). Thus, since prior art teaches a method of treatment of the same disease (mantle cell lymphoma) with the same drug combinations (abemaciclib and copanlisib or gedatolisib), it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the method taught by prior art by selecting and combining various known drugs of known mechanism of action, and applying those combinations to the method of treatment of patients suffering from mantle cell lymphoma to arrive at claimed invention. The one of ordinary skills would be motivated to do so in search of an effective method for treatment of mantle cell lymphoma in patient with the reasonable expectation of success, especially since prior art teaches combinations of PI3K inhibitors with CDK4/6 inhibitors in a method of treatment of mantle cell lymphoma yields beneficial outcomes, such as additive or synergistic effect . 07-22-aia AIA Claim s 9 is rejected under 35 U.S.C. 103 as being unpatentable over Che et al ( Blood (2020) 136 (Supplement 1) : 33) and Stern et al (WO 2015/160986 A2) as applied to claim s 1 – 3, 5 and 15 above, and further in view of Jeon et al (Br J Haematol. 1998 Sep;102(5):1323-6) . Che and Stern teach all the limitations of claim 9 as discussed supra and are applied here in the same manner, except where the mantle cell lymphoma is selected from, or characterized as one of, nodal mantle cell lymphoma; and leukemic non-nodal mantle cell lymphoma. Although Stern does not explicitly specify MCL as nodal mantle cell lymphoma, experimental results of combination therapy taught by Stern were derived using Jeko-1 and Mino cell lines. Furthermore, Jeon teaches characteristics of Jeko-1 cells, where this cell line was established from peripheral blood mononuclear cells taken from a patient with a large cell variant of mantle cell lymphoma (MCL) showing leukaemic conversion (page 1323, “patients and methods”). Thus, combined teachings of Che, Stern and Jeon disclose all the limitations of instant claim 9. Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary . Conclusion 12-151-07 AIA 07-97 12-51-07 Claim s 1 – 15 are rejected. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELENA V VISHNYAKOVA whose telephone number is (571)272-3781. The examiner can normally be reached 7:30am - 5pm ET. 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, RENEE CLAYTOR can be reached at (571)272-8394. 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. /E.V.V./Examiner, Art Unit 1691 /SAVITHA M RAO/Primary Examiner, Art Unit 1691 Application/Control Number: 18/717,529 Page 2 Art Unit: 1691 Application/Control Number: 18/717,529 Page 3 Art Unit: 1691 Application/Control Number: 18/717,529 Page 4 Art Unit: 1691 Application/Control Number: 18/717,529 Page 5 Art Unit: 1691 Application/Control Number: 18/717,529 Page 6 Art Unit: 1691 Application/Control Number: 18/717,529 Page 7 Art Unit: 1691 Application/Control Number: 18/717,529 Page 8 Art Unit: 1691 Application/Control Number: 18/717,529 Page 9 Art Unit: 1691 Application/Control Number: 18/717,529 Page 10 Art Unit: 1691 Application/Control Number: 18/717,529 Page 11 Art Unit: 1691
Prosecution Insights