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 .
Claims 1, 3, 5, 7-15 have been canceled. Claims 16-33 have been added and are under consideration.
The specification remains objected to for failing to conform with the Sequence Rules, above. Applicant’s attention is directed to the specific deficiencies cited in the last Office action:
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located in paragraphs [0247], [0249], [0250], [0252]-[0271], [0289], [0441], [0483], [0485], [0674], [0686], and [0691].
All of the above encompass sequence disclosures lacking SEQ ID NO. s. In the event that the above sequence disclosures are represented in the Sequence Listing and have SEQ ID NO.s, amendment of the specification to incorporate said SEQ ID NO.s, In the even that the above sequence disclosures are not represented in the Sequence Listing,, submission of a new Sequence Listing is required An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Appropriate correction is required.
None of the rejection of claims 1, 3, 7, 8, 9, 13 and 15 under 35 U.S.C. 103 as being unpatentable over Feldmann et al (Onotarget, 2017, Vol. 8, pp. 31368-31385) in view of Polu and Lowman (Expert Opinion on Biological Therapy, 2014, Vol. 14, pp. 1049-1053, reference of the IDS submitted 7/27/2023) as evidenced by Arndt et al (The Prostate, 2014, Vol. 74, pp. 1335-1346);
the rejection of claims 1, 3, 5, 7, 8, 9, 13 and 15 under 35 U.S.C. 103 as being unpatentable over Feldmann et al, Polu and Lowman and Arndt et al as applied to claims 1, 3, 7, 8, 9, 13 and 15 above, and further in view of Ravetch et al (WO2012/087928);
the rejection of claims 1, 3, 7, 8, 9, 11, 12, 13 and 15 under 35 U.S.C. 103 as being unpatentable over Feldmann et al, Polu and Lowman and Arndt et al as applied to claims 1, 3, 7, 8, 9, 13 and 15 above, and further in view of Krah et al (Immunopharmacology and Immunotoxicology, 2016, Vol. 38, pp. 21-28, reference of the IDS filed 2/16/2022); or
the rejection of claims 1, 3, 7, 8, 9 and 13-15 under 35 U.S.C. 103 as being unpatentable over Feldman et al, Polu and Lowman and Arndt et al as applied to claims 1, 3, 7, 8, 9, 13 and 15 above, and further in view of Igawa et al (WO2019/107384, reference of the IDS filed 2/16/2022) as evidenced by Igawa et al (U.S. 2021/0206845, English Language Translation, reference of the IDS filed 2/16/2022d)
will not be applied to the instant new claims, now requiring that “protease cleavage of the linker produces a fragment of the antigen-binding molecule comprising the antigen-binding domain and a portion of the cleaved linker, and exposes a site on the fragment”
to which the extracellular binding domain of the chimeric antigen receptor binds, thereby creating a complex comprising (i) the cell expressing the chimeric receptor and (ii) the fragment that is bound by the chimeric receptor(claim 16),
to which the second arm of the bispecific antibody binds, thereby creating a complex comprising the bispecific antibody bound to the fragment (claim 22), and
to which an antigen-binding arm of the first IgG antibody binds, thereby creating a complex comprising the first IgG antibody bound to the fragment (claim 28).
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.
All other rejections are withdrawn.
Conclusion
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 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