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 .
Election/Restriction
Applicant's election with traverse of Invention I and the HCDRs1-3 for the antibody binding TIGIT (i.e., SEQ ID NOs: 186, 187, and 188, which are comprised in the VH set forth in SEQ ID NO: 189) in the reply filed on 10SEP2025 is acknowledged. The traversal is on the grounds that there is not a serious search burden between Inventions I, II, and III. This is not found persuasive because there is serious search burden between the products, processes of making, and processes of using as set forth in the restriction (election) mailed on 10JUL2025, which shows separate classifications of the inventions and different fields of search (see p 3-5).
The requirement is still deemed proper and is therefore upheld.
Claims 10, 36, 62-63, 88-93, 98-99, and 106 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and/or species. Applicant timely traversed the restriction (election) requirement in the reply filed on 10SEP2025.
Claim Status
Claims 7, 10, 33, 36, 59, 62, 65, 68-69, 71-72, 87-89, 91-93, 98-99, and 106 have been amended.
Claims 1-6, 8-9, 11-32, 34, 37-58, 60-61, 64, 66-67, 70, 73-86, 94-97, 100-105, and 107 have been cancelled.
Claims 7 (independent), 10, 33, 35-36, 59, 62 (independent), 63, 65, 68-69, 71-72, 87-93, 98-99, and 106 are pending in the instant application.
Claims 7, 33, 35, 59, 65, 68-69, 71-72, and 87 are examined on the merits.
Priority
The present application is a continuation of International Application No. PCT/CN2021/070903, filed 08JAN2021, which claims foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of CN202010024565.9 filed on 10JAN2020 has been received and is acknowledged.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 08JUL2022 (2x), 07MAR2024, and 24FEB2025 is/are acknowledged and the references cited therein have been considered.
Claim Objections
Claims 7, 33, 35, 59, 65, 68-69, 71-72, and 87 are objected to because of the following informalities:
Claim 7 contains the acronym “TIGIT” in line one of the claim. While acronyms are permissible as shorthand in the claims, the first recitation of the term should include the full recitation followed by the acronym in parentheses Claims 33, 35, 59, 65, 68-69, 71-72, and 87 are also objected to since they depend from claim 7, but do not remedy this deficiency.
Appropriate correction is required.
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 71-72 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 71-72 are indefinite because they recite “… wherein the IgG1 Fc region comprises mutations of L235V…and P396L, or S239D,..and I332D” which do not correlate to a specific SEQ ID NO or numbering scheme (e.g., Kabat, Clothia, etc.).
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 7, 33, 35, 59, 65, 68-69, 71-72, and 87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,415,858 B2 (application 17/811541), herein referred to as “’858” in view of Mimoto, et al. (Mabs, 2013, 5, 229-236), herein referred to as “Mimoto.”
The independent claim of the instant application recites: An antibody that binds to TIGIT, comprising a single domain antibody that binds to TIGIT with KD of 1x10-7 M or less, wherein the single domain antibody comprises a heavy chain variable region comprising: a) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 94, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 95, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 96, b) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 98, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 99, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 100, c) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 102, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 103, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 104, d) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 106, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 107, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 108, e) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 110, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 111, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 112, f) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 114, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 115, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 116, g) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 118, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 119, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 120, h) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 122, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 123, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 124, i) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 126, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 127, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 128, j) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 130, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 131, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 132, k) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 134, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 135, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 136, I) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 138, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 139, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 140, m) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 142, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 143, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 144, n) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 146, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 147, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 148, o) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 150, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 151, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 152, p) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 154, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 155, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 156, q) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 158, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 159, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 160, r) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 162, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 163, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 164, s) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 166, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 167, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 168, t) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 170, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 171, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 172, u) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 174, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 175, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 176, v) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 178, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 179, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 180, w) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 182, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 183, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 184, x) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 186, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 187, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 188, or y) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 190, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 191, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 192 (i.e., claim 7, emphasis added to denote selected species).
The issued claims of the ‘858 patent recite: A multispecific antibody that binds to T cell immunoreceptor with Ig and ITIM domains (TIGIT) and Programmed cell death ligand-I (PDL1), comprising: i) a first antigen-binding moiety comprising an anti-TIGIT antibody comprising a single domain antibody that binds to TIGIT comprising a heavy chain variable region comprising: a) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 94, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 95, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 96, b) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 98, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 99, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 100, c) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 102, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 103, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 104, d) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 106, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 107, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 108, e) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 110, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 111, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 112, f) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 114, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 115, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 116, g) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 118, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 119, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 120, h) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 122, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 123, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 124, i) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 126, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 127, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 128, j) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 130, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 131, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 132, k) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 134, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 135, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 136, l) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 138, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 139, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 140, m) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 142, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 143, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 144, n) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 146, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 147, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 148, o) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 150, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 151, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 152, p) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 154, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 155, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 156, q) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 158, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 159, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 160, r) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 162, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 163, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 164, s) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 166, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 167, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 168, t) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 170, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 171, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 172, u) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 174, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 175, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 176, v) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 178, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 179, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 180, w) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 182, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 183, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 184, x) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 186, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 187, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 188, or y) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 190, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 191, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 192; and ii) a second antigen-binding moiety comprising an anti-PDL1 antibody that binds to PDL1, wherein the second antigen-binding moiety comprises: a) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 221, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 222, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 223; and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 224, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 225, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 226, b) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 229, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 230, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 231; and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 232, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 233, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 234, c) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 237, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 238, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 239; and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 240, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 241, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 242, d) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 245, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 246, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 247; and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 248, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 249, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 250, e) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 253, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 254, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 255; and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 256, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 257, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 258, f) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 261, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 262, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 263; and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 264, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 265, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 266, g) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 269, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 270, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 271; and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 272, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 273, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 274, h) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 277, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 278, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 279; and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 280, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 281, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 282, i) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 285, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 286, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 287; and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 288, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 289, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 290, or i) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 293, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 294, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 295; and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 296, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 297, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 298 (i.e., claim 1, emphasis added to denote species similarity). The multispecific antibody of claim 1, wherein the single domain antibody comprises a heavy chain variable region comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 97, 101, 105, 109, 113, 117, 121, 125, 129, 133, 137, 141, 145, 149, 153, 157, 161, 165, 169, 173, 177, 181, 185, 189 and 193 (i.e., claim 3, emphasis added to denote species similarity). The multispecific antibody of claim 1, wherein the anti-PDL1 antibody of the second antigen-binding moiety comprises an Fc region selected from the group consisting of the Fc region of IgG1, IgG2, IgG3 and IgG4 (i.e., claim 6). The multispecific antibody of claim 6, wherein the Fc region comprises an IgG1 Fc region (i.e., claim 7). An immunoconjugate comprising the multispecific antibody of claim 1, wherein the therapeutic agent is a cytotoxin or a radioactive isotope (i.e., claim 12). A pharmaceutical composition comprising a) the multispecific antibody of claim 1 and b) a pharmaceutically acceptable carrier (i.e., claim 13). A method of reducing tumor burden in a subject, the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim 13 (i.e., claim 18). A method of treating a neoplasm, the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim 13 (i.e., claim 19). A method of prolonging survival of a subject having a neoplasm, the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim 13 (i.e., claim 20).
In this instance, because the anti-TIGIT antibody component of the ‘858 patent comprising the SEQ ID NOs: 186, 187, and 188 or 189 are 100% query match to SEQ ID NOs: 186, 187, and 188, or 189 of the instant application (see OA.APPENDIX), there is no clear difference in the scope between the products of the ‘858 patent and the instant application.
However, they do not claim: wherein the IgG1 Fc region comprises five (L235V/F243L/R292P/Y300L/P396L) or three (S239D/A330L/I332E) specific mutations.
Nevertheless, Mimoto teach Fc engineered antibody variants, of which the triple substitution variant of the Fc region comprising S239D/A330L/I332E binds FcγRIIIa with higher affinity and superior antibody-dependent cell-mediated cytotoxicity (ADCC) activity than wt IgG and a five substitution variant of the Fc region comprising L235V/F243L/R292P/Y300L/P396L showed enhanced binding to FcγRIIIa, but not to FcγRIIb, which improved the activation binding to inhibition binding ratio (i.e., A/I ratio, an important factor for determining the therapeutic efficacy of an antitumor antibody) (p 229, col 2 to p 230, col 1). Furthermore, Mimoto teach that mAbs promote elimination of tumor cells by Fab-dependent and Fc-dependent mechanisms, such as interference with signaling pathways, apoptosis induction, complement-dependent cytotoxicity, antibody-dependent cell-mediated phagocytosis, and ADCC. ADCC is induced when effector cells are recruited by the Fc domain engaging with a member of the FcγR family and increasing affinity for FcγR enhances ADCC, which results in increased antitumor potency (p 229, col 1 to col 2).
It would have been obvious to artisans to modify the issued products of the anti-TIGIT antibody component of the bispecific antibody comprising specific HCDRs1-3 as set forth in specific SEQ ID NOs having an IgG1 Fc region as claimed by the ‘858 patent to include specific five or three substitution variants, as taught by Mimoto. This is because Mimoto teaches that both the three and five substitution variants perform superiorly to a wt IgG Fc region and in the instance of the five substitution variant showing an improved A/I ratio or enhanced selective binding. One would have been motivated to combine the anti-TIGIT binding component and the specific substitutions of the IgG Fc region, given the direction by the ‘858 patent that the antibodies are to be used to treat cancer, which would benefit from improved ADCC activity. There would have been a reasonable expectation of success, given the knowledge that by modifying the Fc region of an anti-TIGIT antibody taught by the ‘858 patent by IgG Fc modifications would lead to improved ADCC activity for tumor treatment, as taught by Mimoto.
Claims 7, 33, 35, 59, 65, 68-69, 71-72, and 87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 34, 36, 60, 88, 91-93, 100, 104-110, 115-116, and 123 of co-pending Application No. 17/811513, herein referred to as “reference application” in view of Mimoto, et al. (Mabs, 2013, 5, 229-236), herein referred to as “Mimoto.”
The co-pending claims of the reference application recite: A multispecific antibody that binds to T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT) and programmed death protein 1 (PD1), comprising: i) a first antigen-binding moiety comprising an anti-TIGIT antibody comprising a single domain antibody that binds to TIGIT comprising a heavy chain variable region comprising: a) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 94, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 95, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 96, b) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 178, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 179, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 180,… d) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 186, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 187, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 188,.. and ii) a second antigen-binding moiety comprising an anti-PD1 antibody that binds to PD1 comprising:.. wherein the first antigen-binding moiety comprises two anti-TIGIT antibodies, and the second antigen binding moiety comprises an anti-PD1 antibody comprising two antibody heavy chains and two antibody light chains, and wherein the N-terminus of each of the two anti-PD1 heavy chains is linked to an anti-TIGIT antibody of the first antigen binding moiety (i.e., claim 1). The multispecific antibody of claim 1, wherein the single domain antibody comprises a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 186, a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 187, and a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 188 (i.e., claim 34). The multispecific antibody of claim 1, wherein the single domain antibody comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 97, 181,185,189 and 193 (i.e., claim 36). The multispecific antibody of claim 1, wherein the single domain antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 189 (i.e., claim 60). The multispecific antibody of claim 1, wherein the anti-PD1 antibody of the second antigen-binding moiety comprises an Fc region selected from the group consisting of the Fc region of IgG1,IgG2, IgG3 and IgG4 (i.e., claim 88). An immunoconjugate comprising the multispecific antibody of claim 1, linked to a therapeutic agent, wherein the therapeutic agent is a cytotoxin or a radioactive isotope (i.e., claim 104). A pharmaceutical composition comprising a) the multispecific antibody of claim 1 and b) a pharmaceutically acceptable carrier (i.e., claim 105). A method of reducing tumor burden in a subject or treating and/or preventing a neoplasm, or lengthening the survival of a subject having a neoplasm, the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim 105 (i.e., claims 110 and 115-116).
In this instance, because the anti-TIGIT antibody component of the reference application comprising the SEQ ID NOs: 186, 187, and 188 or 189 are 100% query match to SEQ ID NOs: 186, 187, and 188, or 189 of the instant application (see OA.APPENDIX), there is no clear difference in the scope between the products of the reference application and the instant application.
However, they do not claim: wherein the IgG1 Fc region comprises five (L235V/F243L/R292P/Y300L/P396L) or three (S239D/A330L/I332E) specific mutations.
Nevertheless, Mimoto teach Fc engineered antibody variants, of which the triple substitution variant of the Fc region comprising S239D/A330L/I332E binds FcγRIIIa with higher affinity and superior antibody-dependent cell-mediated cytotoxicity (ADCC) activity than wt IgG and a five substitution variant of the Fc region comprising L235V/F243L/R292P/Y300L/P396L showed enhanced binding to FcγRIIIa, but not to FcγRIIb, which improved the activation binding to inhibition binding ratio (i.e., A/I ratio, an important factor for determining the therapeutic efficacy of an antitumor antibody) (p 229, col 2 to p 230, col 1). Furthermore, Mimoto teach that mAbs promote elimination of tumor cells by Fab-dependent and Fc-dependent mechanisms, such as interference with signaling pathways, apoptosis induction, complement-dependent cytotoxicity, antibody-dependent cell-mediated phagocytosis, and ADCC. ADCC is induced when effector cells are recruited by the Fc domain engaging with a member of the FcγR family and increasing affinity for FcγR enhances ADCC, which results in increased antitumor potency (p 229, col 1 to col 2).
It would have been obvious to artisans to modify the issued products of the anti-TIGIT antibody component of the bispecific antibody comprising specific HCDRs1-3 as set forth in specific SEQ ID NOs having an IgG1 Fc region as claimed by the reference application to include specific five or three substitution variants, as taught by Mimoto. This is because Mimoto teaches that both the three and five substitution variants perform superiorly to a wt IgG Fc region and in the instance of the five substitution variant showing an improved A/I ratio or enhanced selective binding. One would have been motivated to combine the anti-TIGIT binding component and the specific substitutions of the IgG Fc region, given the direction by the reference application that the antibodies are to be used to treat cancer, which would benefit from improved ADCC activity. There would have been a reasonable expectation of success, given the knowledge that by modifying the Fc region of an anti-TIGIT antibody taught by the reference application by IgG Fc modifications would lead to improved ADCC activity for tumor treatment, as taught by Mimoto.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641