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US-12617845-B2 - SMC1A antibodies and uses thereof

US12617845B2US 12617845 B2US12617845 B2US 12617845B2US-12617845-B2

Abstract

Provided herein are, inter alia, antibodies capable of binding Structural Maintenance of Chromosome-1 (SMC1). The antibodies provided herein include novel light chain and heavy chain sequences and bind SMC1 (e.g., SMC1A or SMC1B) with high efficiency and specificity. The SMC1 antibodies provided herein including embodiments thereof may be used for diagnostic and therapeutic purposes, for example, as humanized SMC1 antibodies, antibody drug conjugates or they may form part of bispecific antibodies or chimeric antigen receptors.

Inventors

  • Sushma Yadav
  • Arthur RIGGS
  • David Horne
  • John C. Williams

Assignees

  • CITY OF HOPE

Dates

Publication Date
20260505
Application Date
20210514

Claims (10)

  1. 1 . A Structural Maintenance of Chromosome-1 (SMC1) antibody comprising a light chain variable domain and a heavy chain variable domain, wherein said light chain variable domain comprises: a CDR L1 as set forth in SEQ ID NO:1, a CDR L2 as set forth in SEQ ID NO:2 and a CDR L3 as set forth in SEQ ID NO:3; and wherein said heavy chain variable domain comprises: a CDR H1 as set forth in SEQ ID NO:4, a CDR H2 as set forth in SEQ ID NO:5, and a CDR H3 as set forth in SEQ ID NO:6.
  2. 2 . A Structural Maintenance of Chromosome-1 (SMC1) antibody comprising a light chain variable domain and a heavy chain variable domain, wherein said light chain variable domain comprises: a CDR L1 as set forth in SEQ ID NO:7, a CDR L2 as set forth in SEQ ID NO:8 and a CDR L3 as set forth in SEQ ID NO:9; and wherein said heavy chain variable domain comprises: a CDR H1 as set forth in SEQ ID NO:10, a CDR H2 as set forth in SEQ ID NO:11, and a CDR H3 as set forth in SEQ ID NO: 12.
  3. 3 . A Structural Maintenance of Chromosome-1 (SMC1) antibody comprising a light chain variable domain and a heavy chain variable domain, wherein said light chain variable domain comprises: a CDR L1 as set forth in SEQ ID NO:13, a CDR L2 as set forth in SEQ ID NO:14 and a CDR L3 as set forth in SEQ ID NO:15; and wherein said heavy chain variable domain comprises: a CDR H1 as set forth in SEQ ID NO:16, a CDR H2 as set forth in SEQ ID NO:17, and a CDR H3 as set forth in SEQ ID NO: 18.
  4. 4 . A Structural Maintenance of Chromosome-1 (SMC1) antibody comprising a light chain variable domain and a heavy chain variable domain, wherein said light chain variable domain comprises: a CDR L1 as set forth in SEQ ID NO:19, a CDR L2 as set forth in SEQ ID NO:20 and a CDR L3 as set forth in SEQ ID NO:21; and wherein said heavy chain variable domain comprises: a CDR H1 as set forth in SEQ ID NO:22, a CDR H2 as set forth in SEQ ID NO:23, and a CDR H3 as set forth in SEQ ID NO:24; or a CDR H1 as set forth in SEQ ID NO:25, a CDR H2 as set forth in SEQ ID NO:26, and a CDR H3 as set forth in SEQ ID NO:27.
  5. 5 . The SMC1 antibody of any one of claims 1-4 , wherein said light chain variable domain comprises the sequence of SEQ ID NO:28, SEQ ID NO:30, or SEQ ID NO:32.
  6. 6 . The SMC1 antibody of any one of claims 1-4 , wherein said heavy chain variable domain comprises the sequence of SEQ ID NO:29, SEQ ID NO:31, or SEQ ID NO:33.
  7. 7 . A recombinant protein comprising: (i) a first antibody region capable of binding an effector cell ligand; and (ii) a second antibody region, comprising: (a) a second light chain variable domain comprising a CDR L1 as set forth in SEQ ID NO:1, a CDR L2 as set forth in SEQ ID NO:2 and a CDR L3 as set forth in SEQ ID NO:3; a CDR L1 as set forth in SEQ ID NO:7, a CDR L2 as set forth in SEQ ID NO:8 and a CDR L3 as set forth in SEQ ID NO:9; a CDR L1 as set forth in SEQ ID NO:13, a CDR L2 as set forth in SEQ ID NO:14 and a CDR L3 as set forth in SEQ ID NO:15; or a CDR L1 as set forth in SEQ ID NO:19, a CDR L2 as set forth in SEQ ID NO:20 and a CDR L3 as set forth in SEQ ID NO:21; and (b) a second heavy chain variable domain comprising a CDR H1 as set forth in SEQ ID NO:4, a CDR H2 as set forth in SEQ ID NO:5, and a CDR H3 as set forth in SEQ ID NO:6; a CDR H1 as set forth in SEQ ID NO:10, a CDR H2 as set forth in SEQ ID NO:11, and a CDR H3 as set forth in SEQ ID NO:12; a CDR H1 as set forth in SEQ ID NO:16, a CDR H2 as set forth in SEQ ID NO:17, and a CDR H3 as set forth in SEQ ID NO:18; a CDR H1 as set forth in SEQ ID NO:22, a CDR H2 as set forth in SEQ ID NO:23, and a CDR H3 as set forth in SEQ ID NO:24; or a CDR H1 as set forth in SEQ ID NO:25, a CDR H2 as set forth in SEQ ID NO:26, and a CDR H3 as set forth in SEQ ID NO:27.
  8. 8 . The recombinant protein of claim 7 , wherein said second light chain variable domain comprises the sequence of SEQ ID NO:28, SEQ ID NO:30 or SEQ ID NO:32.
  9. 9 . The recombinant protein of claim 7 , wherein said second heavy chain variable domain comprises the sequence of SEQ ID NO:29, SEQ ID NO:31 or SEQ ID NO:33.
  10. 10 . A method of detecting a cancer cell said method comprising contacting a cancer cell with a SMC1 antibody of any one of claims 1-4 , thereby forming an antibody-cell conjugate and detecting said antibody-cell conjugate.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS This application is a national stage filing under USC 371 of International Application No. PCT/US2021/032633, filed May 14, 2021, which claims priority to U.S. Application No. 63/024,991 filed May 14, 2020, the disclosure of which are incorporated by reference herein in their entirety. REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED AS AN ASCII FILE The Sequence Listing written in file 048440-766001WO_Sequence Listing_ST25.TXT, created on May 13, 2021, 29,483 bytes, machine format IBM-PC, MS Windows operating system, is incorporated herein by reference. BACKGROUND OF THE INVENTION Although tremendous progress has been made in the field of cancer immunotherapy for both hematological and solid tumors, lack of cancer-specific cell surface markers in aggressive cancers has resulted in a death of targeted therapies and poor patient outcomes. The compositions and methods provided herein address these and other needs in the art.dea BRIEF SUMMARY OF THE INVENTION In a first aspect is provided a Structural Maintenance of Chromosome-1 (SMC1) antibody including a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain includes: a CDR L1 as set forth in SEQ ID NO:1, a CDR L2 as set forth in SEQ ID NO:2 and a CDR L3 as set forth in SEQ ID NO:3; and wherein the heavy chain variable domain includes: a CDR H1 as set forth in SEQ ID NO:4, a CDR H2 as set forth in SEQ ID NO:5, and a CDR H3 as set forth in SEQ ID NO:6. In another aspect is provided a Structural Maintenance of Chromosome-1 (SMC1) antibody including a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain includes: a CDR L1 as set forth in SEQ ID NO:7, a CDR L2 as set forth in SEQ ID NO:8 and a CDR L3 as set forth in SEQ ID NO:9; and wherein the heavy chain variable domain includes: a CDR H1 as set forth in SEQ ID NO:10, a CDR H2 as set forth in SEQ ID NO:11, and a CDR H3 as set forth in SEQ ID NO:12. In another aspect is provided a Structural Maintenance of Chromosome-1 (SMC1) antibody including a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain includes: a CDR L1 as set forth in SEQ ID NO:13, a CDR L2 as set forth in SEQ ID NO:14 and a CDR L3 as set forth in SEQ ID NO: 15; and wherein the heavy chain variable domain includes: a CDR H1 as set forth in SEQ ID NO:16, a CDR H2 as set forth in SEQ ID NO:17, and a CDR H3 as set forth in SEQ ID NO:18. In another aspect is provided a Structural Maintenance of Chromosome-1 (SMC1) antibody including a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain includes: a CDR L1 as set forth in SEQ ID NO:19, a CDR L2 as set forth in SEQ ID NO:20 and a CDR L3 as set forth in SEQ ID NO:21; and wherein the heavy chain variable domain includes: a CDR H1 as set forth in SEQ ID NO:22, a CDR H2 as set forth in SEQ ID NO:23, and a CDR H3 as set forth in SEQ ID NO:24; or a CDR H1 as set forth in SEQ ID NO:25, a CDR H2 as set forth in SEQ ID NO:26, and a CDR H3 as set forth in SEQ ID NO:27. In another aspect is provided a Structural Maintenance of Chromosome-1 (SMC1) antibody including a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain includes: a CDR L1 as set forth in SEQ ID NO:39, a CDR L2 as set forth in SEQ ID NO:40 and a CDR L3 as set forth in SEQ ID NO:41; and wherein the heavy chain variable domain includes: a CDR H1 as set forth in SEQ ID NO:42, a CDR H2 as set forth in SEQ ID NO:43, and a CDR H3 as set forth in SEQ ID NO:44. In another aspect is provided a recombinant protein including: (i) a first antibody region capable of binding an effector cell ligand; and (ii) a second antibody region, including: (a) a second light chain variable domain including a CDR L1 as set forth in SEQ ID NO: 1, a CDR L2 as set forth in SEQ ID NO:2 and a CDR L3 as set forth in SEQ ID NO: 3; a CDR L1 as set forth in SEQ ID NO:7, a CDR L2 as set forth in SEQ ID NO:8 and a CDR L3 as set forth in SEQ ID NO: 9; a CDR L1 as set forth in SEQ ID NO:13, a CDR L2 as set forth in SEQ ID NO:14 and a CDR L3 as set forth in SEQ ID NO:15; or a CDR L1 as set forth in SEQ ID NO:19, a CDR L2 as set forth in SEQ ID NO:20 and a CDR L3 as set forth in SEQ ID NO:21; and (b) a second heavy chain variable domain including a CDR H1 as set forth in SEQ ID NO:4, a CDR H2 as set forth in SEQ ID NO:5, and a CDR H3 as set forth in SEQ ID NO:6; a CDR H1 as set forth in SEQ ID NO:10, a CDR H2 as set forth in SEQ ID NO:11, and a CDR H3 as set forth in SEQ ID NO:12; a CDR H1 as set forth in SEQ ID NO:16, a CDR H2 as set forth in SEQ ID NO:17, and a CDR H3 as set forth in SEQ ID NO: 18; a CDR H1 as set forth in SEQ ID NO:22, a CDR H2 as set forth in SEQ ID NO:23, and a CDR H3 as set forth in SEQ ID NO:24; or a CDR H1 as set forth in SEQ ID NO:25, a