NOVEL CAR

§103 §112

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 Applicant’s amendment filed on 04/08/2025 is acknowledged. Following the amendment, claims 48, and 50-51 are cancelled without prejudice or disclaimer. Claims 2-4, 15, 21, 25, 29-30, and 46 are amended. Claims 58-61 were added. Claims 1-4, 7-10, 13, 15, 19, 21, 25, 29-33, 43-44, 46-47, 54, and 58-61 are currently pending and under examination. Specification Applicant’s arguments, see pg. 15, filed 04/08/2025, with respect to the specification have been fully considered and are persuasive. The objection of the specification has been withdrawn. Claim Objections Applicant’s arguments, see pg. 15, filed 04/08/2025, with respect to claims 29 and 30 have been fully considered and are persuasive. The objection of claims 29 and 30 has been withdrawn. Claim Rejections - 35 USC § 112 Applicant’s arguments, see pgs. 15-16, filed 04/08/2025, with respect to claims 2-3, 15, 21, 25, 29-30, and 46 have been fully considered and are persuasive. The rejection of claims 2-3, 15, 21, 25, 29-30, and 46 has been withdrawn. 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. 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 1-4, 7-10, 13, 15, 19, 21, 25, 29-33, 43-44, 46-47, 54, and 58-61 remain rejected under 35 U.S.C. 103 as being unpatentable over Kershaw et al (WO2020087116), as evidenced by Hopp et al (US4703004), in view of Terrett et al (WO2009045957). Applicant's arguments filed 04/08/2025 have been fully considered but they are not persuasive. On pg. 17 of Applicant remarks, Applicant makes the case that the Examiner has failed to clearly articulate a reason why a person of ordinary skill in the art would have selected the specific antigen binding domain sequences as disclosed in Terrett for incorporation into a CAR molecule as disclosed in Kershaw. 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, Kershaw teaches generic CAR constructs (paragraphs 0063-0066; 0076-0078) and also gives examples of specific CAR constructs against Her2 antigen (paragraphs 0171, 0214, 0216) and against carcinoembryonic antigen (CEA) (paragraph 0220). As described previously in the office action dated 01/08/2025 (see pgs. 8-9), Kershaw teaches the various limitations of CAR design as disclosed by claims 7-8, 10, 13, 15, 19, 21, 25, and 29-32 in the instant application. Terrett discloses human anti-mesothelin monoclonal antibodies, particularly, 7B1, which has a 100% VH and VL scFv sequence identity to the VH and VL sequences of the antigen recognition domain within the CAR construct as presented in claim 1 of the instant application. Terrett also teaches that 7B1 has high affinity to human mesothelin, rapid internalization by cells expressing mesothelin, and mediation of antibody dependent cellular cytotoxicity (ADCC) (lines 14-20, pg. 2). Furthermore, it was well known at the time of the invention and routine to convert high-affinity antibodies into CAR scFvS for solid tumor targets (see Beatty et al., 2014, Cancer Immunology Research, 2(2):112-120; see also WO2015090230). Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected the high-affinity mesothelin sequences (7B1 VH/VL) of Terrett, fuse them with a linker peptide such as (G4S)3 to create an scFv, and substitute that scFv for the generic CAR construct taught by Kershaw. Doing so would obtain the presently claimed mesothelin-targeting CAR of the present application with no change in function and would have been a predictable design choice incorporating the addition of a known element (an scFv derived from a high-affinity mesothelin antibody) into a generic CAR thereby optimizing overall CAR construction for antigen capture, anti-tumor cell toxicity, and treatment efficacy for cancer types that exhibit growth of mesothelin-expressing tumor cells. In addition, Applicant makes the argument that a person of ordinary skill in the art would not have sought to include the 7B1 antibody sequences disclosed by Terrett as scFv fragments into a CAR for treating a cancer expressing mesothelin (see pg. 17-18 of Applicant remarks filed 04/08/2025). The Applicant uses Examples 5 and 6 from Terrett to support these arguments. These examples showed that 7B1 was internalized less well by the KB cell line than the other two antibodies and that 7B1 did not exhibit the ability to inhibit the interaction of mesothelin with CA 125, an ovarian cancer cell line. Applicant concludes that a person of ordinary skill in the art would have sought include another antibody such as 6A4 with more desirable characteristics rather than the 7B1 antibody. Examiner finds this line of reasoning unpersuasive because Terrett notes that 7B1 binds to an epitope distinct from the other two mesothelin antibodies (see lines 14-17, Example 3), but still displays high affinity to binding human mesothelin (lines 1-4, Example 3A; lines 21-23, Example 3B). Terrett also teaches that 7B1 is as stable as the lead 6A4 antibody in chemical and thermal stability profiling (Example 4), and demonstrated positive cytotoxic payload ferrying capabilities with its positive internalization of ADCC saporin kill in CHO mesothelin cell lines (Example 5). Therefore, while 7B1 may not have the same epitope binding on mesothelin as the lead candidate 6A4, this does not automatically invalidate its capabilities for anti-tumor properties against mesothelin expressing tumor cells as its unique epitope binding may make it a more potent candidate for better targeting of mesothelin expressing cancer types that are less responsive to the other antibody candidates. Conclusion No claim is allowable. THIS ACTION IS MADE FINAL. 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 DENNIS GEORGE whose telephone number is (571)270-0340. The examiner can normally be reached M-F 8:30am - 5pm 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, Daniel E Kolker can be reached at (571) 272-3181. 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. /DENNIS GEORGE/Examiner, Art Unit 1644 /DANIEL E KOLKER/ Supervisory Patent Examiner, Art Unit 1644