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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 13, 2025 has been entered.
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 27, 33, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Radosevich et al. (WO 2011/116014 A2; Published: Sep 22, 2011) in view of Chang et al. (US 2018/0142034 A1; Published: May 24, 2018).
Radosevich et al. teaches humanized anti-Labyrinthin antibodies which can be part of a pharmaceutical composition which further comprises a pharmaceutically acceptable carrier; see paragraphs 00126, 00174-00175, and 00187-00188 and claims 1-5, 12 19. Regarding the CDRs of the anti-Labyrinthin construct in claim 27, Radosevich et al. teaches an anti-Labyrinthin construct comprising CDRs of SEQ ID NOs: 11-16 which are 100% identical to instant SEQ ID NOs: 33-38, respectively.
Further regarding claims 33 and 34, Radosevich et al. teaches treating Labyrinthin-positive cancers, specifically, adenocarcinoma by administering an effective amount of the anti-Labyrinthin antibody; see paragraphs 00182-00186, 00188, and 00194-00195, and claims 37-50.
Radosevich et al. does not teach the anti-Labyrinthin antibody as an antibody moiety in a chimeric antigen receptor construct.
Chang et al. teaches compositions of chimeric antigen receptors (CARs) comprising an antigen binding domain, a transmembrane domain, and a cytoplasmic domain; see Abstract. Chang et al. teaches that the antigen binding domain comprises an scFv domain; see Figure 1 and paragraph 0159. The targets of the antigen binding domain may be any antigen over-expressed in target or disease cells, including cancer-specific antigens; see paragraphs 0156-0157. Exemplified antigens are not restricted to those found exclusively on hematological cancers, but include solid tumor targets such as HER2; see paragraph 0157. In fact, Chang et al. teaches using an IL-15Rα endodomain to produce so called 153z CAR T cells with rapid killing efficacy for use in solid tumors; see paragraph 0320.
Given that Radosevich et al. teaches that Labyrinthin is a cell surface protein expressed on the extracellular surface of the plasma membrane of adenocarcinomas and is not in the serum of normal or tumor bearing patients making it an adenocarcinoma-specific marker (see paragraph 0003) and that Chang et al. teaches treating solid tumors using CAR T-cells engineered to target a cell surface marker, it would have been obvious to one of ordinary skill in the art to combine the scFv taught by Radosevich et al. (Figure 1) as the antigen binding domain of the CAR T-cell taught by Chang et al. One would be motivated to make and use the anti-Labyrinthin CAR T-cells over anti-Labyrinthin antibodies because CAR T-cells are capable of replicating in vivo to generate a prolonged anti-tumor response; see Chang et al. paragraph 0087. Finally, one of ordinary skill in the art would have had a reasonable expectation of success because Radosevich et al. teaches that Labyrinthin is a cell surface marker in adenocarcinoma and Examples 3 and 4 demonstrate that CAR T-cells can successfully target cell surface markers on solid tumors.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Response to Arguments
Applicant’s amendments filed May 13, 2025 are acknowledged. Any rejection not repeated above is resolved by amendment. Note that the nonstatutory double patenting rejections over the claims of U.S. Patent Nos. 6,727,080 B1; 7,635,759 B2; or 8,163,883 B2 are overcome by the amendment requiring the CDRs of SEQ ID NOs: 33-38. The claims of U.S. Patent Nos. 6,727,080 B1; 7,635,759 B2; or 8,163,883 B2 recite a genus of antibodies binding epitopes. The Specifications of U.S. Patent Nos. 6,727,080 B1; 7,635,759 B2; or 8,163,883 B2 do not evidence that Applicant was in possession of the species instantly claimed. Further, while the instant Specification teaches overlapping epitopes (see page 28), it does not teach to exactly which residues within the portion of Labyrinthin comprising SEQ ID NO: 1 the species instantly claimed binds.
Regarding the rejection under U.S.C. 103, Applicant argues that Radosevich et al. only demonstrates the binding of the anti-Labyrinthin antibody to His-tagged Labyrinthin in vitro. Applicant suggests that His-tagged Labyrinthin in vitro may have a conformation distinct from its native conformation to which the anti-Labyrinthin moiety need bind to achieve the claimed method.
Radosevich et al. teaches an anti-Labyrinthin antibody comprising CDRs 100% identical to that instantly claimed. Radosevich et al. states that affinity was measured using standard techniques; see the third line of paragraph 00223 Example 1. One of ordinary skill in the art would have a reasonable expectation of success that the anti-Labyrinthin antibody binds Labyrinthin based on the use of standard techniques to demonstrate binding affinity. Additionally, instant Figure 2 evidences that the anti-Labyrinthin antibody comprising the CDRs of SEQ ID NOs: 33-38 does bind native, or non-His-tagged, Labyrinthin.
Moreover, Applicant provides no objective evidence or sound scientific reasoning to support such a contention; rather, it appears to be nothing more than an attorney argument. As set forth in the MPEP at 2145, "The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”).”
The rejection of claims 27, 33, and 34 under 35 U.S.C. 103 as being unpatentable over Radosevich et al. in view of Chang et al. is maintained.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Babich et al. (The FASEB Journal. 20(5): pLB109; Published: May 7, 2006) teaches anti-Labyrinthin antibodies, optionally cytotoxin-conjugated, for treating adenocarcinoma, which expresses Labyrinthin.
Loeb et al. (US 2011/0230433 A1; Published: Sep 22, 2011) teaches treating cancer comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a mutagenic compound; see claims 7-19. Here, "mutagenic compound" refers to a compound that can increase the mutation frequency in the genome of a mammalian cell, influence the fidelity of a nucleic acid replication process, influence a nucleic acid repair process, and/or influence the balance of the nucleotide pool, such as mutagenic nucleoside analogs, which result in nuclear mutations and ablation of tumor cells; see paragraphs 0149 and 0183-0185. The composition taught by Loeb et al. may further comprise a tumor antigen targeting agent, optionally targeting Labyrinthin, to reduce potential side effects; see paragraphs 0114-0115. Paragraph 0106 teaches that the composition further comprises a pharmaceutically acceptable carrier.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE ANN HOLTZMAN whose telephone number is (571)270-0252. The examiner can normally be reached Monday - Friday 7:30am - 5:00pm.
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/KATHERINE ANN HOLTZMAN/Examiner, Art Unit 1644
/JULIET C SWITZER/Primary Examiner, Art Unit 1682