DETAILED ACTION
Applicants claim amendments filed 5/4/2023 are acknowledged and entered into the record.
Accordingly, Claims 1, 18, 20, 30-32, 34-36, 38-47 are pending and will be examined on the merits.
The present application is being examined under the pre-AIA first to invent provisions.
Sequence Compliance
This application contains sequence disclosures that are encompassed by 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 through 1.825 for the reason(s) set forth below. Instant Claim 20 recites linker sequences comprising peptide sequences over 4 amino acids without corresponding sequence identifiers (“SEQ ID NO:”). The specification and claims must be revised to comply with 37 CFR 1.821(d), which requires the use of sequence identifiers wherever reference is made to peptide sequences (including those having “X”) of over 4 amino acids. Each linker wherein n is 1 to 10 requires a separate SEQ ID NO: identifier.
Claim Rejections - 35 USC § 112
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.
Claims 1 and 30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: the numbering system used to determine the position of the CDRs within the variable region, ex. Abm, IGMT, Kabat, Chothia, etc. The metes and bounds of the specific CDR regions claimed is unclear based on the lack of recitation of which numbering system is being utilized.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1, 18, 20, 30-32, 34-36, 38-47 are rejected under pre-AIA 35 U.S.C. 103(a) as being obvious over Sahin et al. (US Patent 9,487,584) in view of Kufer et al. (US Patent 7,635,472).
The applied reference has a common inventor with the instant application. Based upon the earlier effective U.S. filing date of the reference, it constitutes prior art under pre-AIA 35 U.S.C. 102(e). This rejection under pre-AIA 35 U.S.C. 103(a) might be overcome by: (1) a showing under 37 CFR 1.132 that any invention disclosed but not claimed in the reference was derived from the inventor of this application and is thus not an invention “by another”; (2) a showing of a date of invention for the claimed subject matter of the application which corresponds to subject matter disclosed but not claimed in the reference, prior to the effective U.S. filing date of the reference under 37 CFR 1.131(a); or (3) an oath or declaration under 37 CFR 1.131(c) stating that the application and reference are currently owned by the same party and that the inventor or joint inventors (i.e., the inventive entity) named in the application is the prior inventor under pre-AIA 35 U.S.C. 104 as in effect on March 15, 2013, together with a terminal disclaimer in accordance with 37 CFR 1.321(c). This rejection might also be overcome by showing that the reference is disqualified under pre-AIA 35 U.S.C. 103(c) as prior art in a rejection under pre-AIA 35 U.S.C. 103(a). See MPEP §§ 706.02(l)(1) and 706.02(l)(2).
The claims are drawn to a bispecific antibody binding CLDN6 and CD3, nucleic acids encoding said bispecific antibody and method of treating cancer comprising administering said bispecific antibody which binds to claudin (CLDN6) and CD3 comprising variable regions having SEQ ID NOs: recited in the instant claims or CDR regions comprised within the variable regions.
Sahin et al. teach therapeutic methods of treating diseases associated with cells expressing Claudin-6 (CLDN6) comprising administering anti-CLDN6 antibodies as well as bispecific antibodies which bind to CLDN6 and CD3. Sahin et al. disclose “bispecific and multispecific molecules that bind to both CLDN6 and to an Fc receptor or a T cell receptor, e.g. CD3”. Additionally, Sahin et al. teach “the bispecific and multispecific molecules of the invention comprise as a binding specificity at least one antibody, including, e.g., an Fab, Fab', F(ab').sub.2, Fv, or a single chain Fv” and “bivalent, bispecific antibodies in which the VH and VL domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen binding sites”. Sahin et al. teaches the specific claudin antibody VH and VL sequences (SEQ ID NOs: 20-29) binding CLDN6, but does not teach the specific CD3 binding VH/VL antibody sequences comprising the variable regions recited in the instant claims. These deficiencies are made up for by Kufer et al.
Kufer et al. teach anti-CD3 antibodies which recognize the CD3-epsilon chain. Kufer et al. teach “bispecific antibodies thus far available suffer from low T-cell cytotoxicity and the need of costimulatory agents in order to display satisfactory biological activity. The CD3 complex denotes an antigen that is expressed on T-cells as part of the multimolecular T-cell receptor complex”. Kufer et al. teaches 100% identity to instantly claimed CD3 targeting variable regions having SEQ ID NOs: 36 and 37. Kufer et al. further discloses linker sequences used to connect the single chain constructs of the bispecific antibodies, including the sequence GGGGS and (GGGGS)3 (see SEQ ID NOs: 69 and 71 of Kufer).
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 make and use the specific "CLDN6” antibody taught by Sahin et al. (A) and the anti-CD3 antibody taught by Kufer et al. in a method of treating cancer by administering a bispecific antibody comprising the two. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on the teachings of Sahin et al. and Kufer et al. because claudin, specifically claudin 6, is widely known in the prior art as an antigen localized to various tumors and a target for development of therapeutic antibodies and the strategy of using binding molecules which react with CD3 positive T-cells in order to improve the killing of the target tumor cells is also well known practice to one of ordinary skill in the art. It would have been obvious to extend the teachings of Sahin et al. to make and use the specific CD3 antibodies taught by Kufer et al. in a bispecific antibody format as taught by Sahin et al. targeting both CLDN6 and CD3 for cancer treatment therapy.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 18, 20, 30-32, 34-36, 38-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 10,717,780. Although the claims at issue are not identical, they are not patentably distinct from each other because US Patent 10,717,780 is drawn to the same method of treatment comprising administering the same bispecific antibody targeting CLDN6 and CD3 as instantly claimed.
Claims 1, 18, 20, 30-32, 34-36, 38-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-16 of U.S. Patent No. 10,233,253 in view of Kufer et al. (US Patent 7,635,472).
Claims 9-16 of US Patent 10,233,253 are drawn to a bispecific or multispecific antibody comprising the anti-CLDN6 antibody instantly claimed having 100% identity to instant SEQ ID NOs: 21 and 22 and an anti-CD3 antibody. The claims of US Patent 10,233,253 do not recite the specific VH/VL or CDR regions instantly claimed for targeting CD3, however this deficiency is made up for by Kufer et al.
Kufer et al. teach anti-CD3 antibodies which recognize the CD3-epsilon chain. Kufer et al. teach “bispecific antibodies thus far available suffer from low T-cell cytotoxicity and the need of costimulatory agents in order to display satisfactory biological activity. The CD3 complex denotes an antigen that is expressed on T-cells as part of the multimolecular T-cell receptor complex”. Kufer et al. teaches 100% identity to instantly claimed CD3 targeting variable regions having SEQ ID NOs: 36 and 37. Kufer et al. further discloses linker sequences used to connect the single chain constructs of the bispecific antibodies, including the sequence GGGGS and (GGGGS)3 (see SEQ ID NOs: 69 and 71 of Kufer).
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 make and use the multispecific CLDN6xCD3 antibody taught by US Patent 10,233,253 using the specific anti-CD3 antibody sequence taught by Kufer et al. in a method of treating cancer by administering a bispecific antibody comprising the two. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on the teachings of Kufer et al. to make and use bispecific binding molecules which react with CD3 positive T-cells in order to improve the killing of the target tumor cells.
Conclusion
Claims 1, 18, 20, 30-32, 34-36, 38-47 are rejected.
No Claim is allowed.
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/Meera Natarajan/Primary Examiner, Art Unit 1643