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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/1/2026 has been entered.
Claims 16, 22 and 28 have been amended. Claims 16-33 are pending and under consideration.
The objection to the specification for failing to conform with the Sequence Rules is withdrawn in light of applicant’s submission of a new CRF and amended specification, and the statement that the amendments to the spec and new sequence listing do not introduce new matter.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 16-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Section 2163 of the M.P.E.P. states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention.
The instant claims are reliant on a genus of extracellular binding domains of a CAR, a bispecific antibody and a first IgG antibody, all of which require binding to an exposed site on a fragment resulting from protease cleavage of a linker inserted between the variable region and the constant region, or inserted between CH1 and CH2 domains. The claims do not limit the protease. Claims 18, 24 and 30 require that the linker comprises a peptide having the protease cleavage sequences of SEQ ID NO: 1-725.
The specification describes
Antibody arm 20A10H-F760nN17/20A10L-k0MT binding to the end of collagen II peptide cleavable by MMP13 or the like (WO2011/034128) was prepared by coexpressing heavy chain 20A10H-F760nN17 having heavy chain variable region 20A10H (SEQ ID NO: 726) and heavy chain constant region F760nN17 (SEQ ID NO: 727) in combination with light chain 20A10L-k0MT having light chain variable region 20A10L (SEQ ID NO: 728) and light chain constant region k0MT (SEQ ID NO: 729) in combination (paragraph [1192]); and
Antibody arm 20952H-F760nN17/20952L-k0MTC binding to the end of human IgG1 peptide cleavable by IdeS (WO2012/067624) was prepared by coexpressing heavy chain 20952H-F760nN17 having heavy chain variable region 20952H (SEQ ID NO: 730) and heavy chain constant region F760nN17 (SEQ ID NO: 727) in combination with light chain 20952L-k0MTC having light chain variable region 20952L (SEQ ID NO: 731) and light chain constant region k0MTC (SEQ ID NO: 746) in combination (paragraph [1193]).
It is noted that stating the required binding site, is not commensurate with a written description of a CAR, a bispecific antibody arm or an IgG that binds to the required binding site because it is not possible to envisage the paratope responsible for binding to an epitope, and one of skill in the art would not envisage the structure of the antibody arm binding to any fragment of a linker cleavable by a protease other than the Antibody arm 20952H-F760nN17/20952L-k0MTC binding to the end of human IgG1 peptide cleavable by IdeS or Antibody arm 20A10H-F760nN17/20A10L-k0MT binding to the end of collagen II peptide cleavable by MMP13 as one could do with a well-described genus. Further the peptides of SEQ ID NO: 1-725 comprising cleavage sites are all 12-mer peptides. It would be expected, that because of the small size of the fragment resulting from the cleavage, that the antibody epitope fragment would likely encompass a portion of the variable region, a portion of the CH1 , a portion of the CH2 or a portion of the constant region to which the linker was attached. The description of the Antibody arm 20952H-F760nN17/20952L-k0MTC or the Antibody arm 20A10H-F760nN17/20A10L-k0MT fail to describe the required genuses because the genuses are highly varied encompassing antibodies biding to widely different epitopes, including epitopes overlapping the residual fragment resulting from protease cleavage of the 12-mer peptide joined to portions of the variable region, a portion of the CH1, a portion of the CH2 or a portion of the constant region to which the linker was attached. One of skill in the art would reasonably conclude that applicant was not in possession of the genuses of CAR, a bispecific antibody arm or an IgG that binds to the required fragment after protease cleavage at the time of filing.
Applicant argues that the claims have been amended to describe more precisely that nature of the fragment of the fragment produced by the protease cleavage of the inker: that the cleavage exposes a peptide terminus on the fragment and the extracellular binding domain of a CAR binds to the exposed peptide terminus. Applicant points out that example 8 of the specification describes procedures for obtaining a molecule that binds to an exposed peptide terminus of the cleaved linker but does not bind to the peptide in an uncleaved linker. This has been considered but not found persuasive. The instant claims are not rejected for lack of enablement regarding how to make and use, but for lacking written description of the antigen binding domain of the CAR which will bind to the exposed peptide after protease cleavage of the linker, but not bind to the intact linker.
All claims are rejected.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
