Novel ddr1 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2023235078-A1
Application number	US-202318176072-A
Country	US
Kind code	A1
Filing date	Feb 28, 2023
Priority date	Dec 17, 2019
Publication date	Jul 27, 2023
Grant date	—

Abstract

The present disclosure relates to antibodies binding to tumor discoidin domain receptor 1 (DDR1) and the uses of the antibodies in detecting and treating cancer.

First claim

What is claimed is:

1 . A monoclonal antibody or antigen-binding fragment thereof that specifically binds to discoidin domain receptor 1 (DDR1) protein, comprising a light chain variable region comprising a LC-CDR1, LC-CDR2 and LC-CDR3 within the light chain variable region, wherein the light chain variable region comprises an amino acid sequence selected from SEQ ID NOs:108-128, and a heavy variable region comprising a HC-CDR1, HC-CDR2, and HC-CDR3 within the heavy chain variable region, wherein the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NOs:129-149, or variants thereof wherein one or more of the LC-CDRs and/or HC-CDRs comprises one, two, or three amino acid substitutions, additions, deletions, or combinations thereof.

2 . The monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the LC-CDR1, LC-CDR2 and LC-CDR3 are a clone paired-set selected from Table 1 and the HC-CDR1, HC-CDR2, and HC-CDR3 are a clone-paired set selected from Table 2, or variants thereof wherein one or more of the LC-CDRs and/or HC-CDRs comprises one, two, or three amino acid substitutions, additions, deletions, or combinations thereof.

3 . The monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the LC-CDR1 comprises the amino acid sequence of SEQ ID NO:11, the LC-CDR2 comprises the amino acid sequence GVF, the LC-CDR3 comprises the amino acid sequence of SEQ ID NO:12, the HC-CDR1 comprises the amino acid sequence of SEQ ID NO:57, the HC-CDR2 comprises the amino acid sequence of SEQ ID NO:58, and the HC-CDR3 comprises the amino acid sequence of SEQ ID NO:59 (DDR1-9), or variants thereof wherein one or more of the LC-CDRs and/or HC-CDRs comprises one, two, or three amino acid substitutions, additions, deletions or combinations thereof.

4 . The monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the LC-CDR1 comprises the amino acid sequence of SEQ ID NO:41, the LC-CDR2 comprises the amino acid sequence QAS, the LC-CDR3 comprises the amino acid sequence of SEQ ID NO:42, the HC-CDR1 comprises the amino acid sequence of SEQ ID NO:102, the HC-CDR2 comprises the amino acid sequence of SEQ ID NO:103, and the HC-CDR3 comprises the amino acid sequence of SEQ ID NO:104 (DDR1-33), or variants thereof wherein one or more of the LC-CDRs and/or HC-CDRs comprises one, two, or three amino acid substitutions, additions, deletions, or combinations thereof.

5 . The monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the light chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 108-128, and the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 129-149.

6 . The monoclonal antibody or antigen-binding fragments thereof of claim 1 , wherein:
(a) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 108 (DDR1-1K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 129 (DDR1-1H); (b) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 109 (DDR1-3K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 130 (DDR1-3H); (c) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 110 (DDR1-5K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 131 (DDR1-5H); (d) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 111 (DDR1-6K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 132 (DDR1-6H); (e) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 112 (DDR1-9K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 133 (DDR1-9H); (f) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 113 (DDR1-11K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 134 (DDR1-11H); (g) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 114 (DDR1-12K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 135 (DDR1-12H); (h) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 115 (DDR1-13K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 136 (DDR1-13H); (i) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 116 (DDR1-14K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137 (DDR1-14H); (j) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 117 (DDR1-15K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 138 (DDR1-15H); (k) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 118 (DDR1-17K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 139 (DDR1-17H); (l) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 119 (DDR1-20K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 140 (DDR1-20H); (m) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 120 (DDR1-21K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 141 (DDR1-21H); (n) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 121 (DDR1-22K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 142 (DDR1-22H); (o) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 122 (DDR1-23K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 143 (DDR1-23H); (p) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 123 (DDR1-26K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 144 (DDR1-26H); (q) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 124 (DDR1-28K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 145 (DDR1-28H); (r) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 125 (DDR1-29K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 146 (DDR1-29H); (s) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 126 (DDR1-32K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 147 (DDR1-32H); (t) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 127 (DDR1-33K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 148 (DDR1-33H); or (u) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 128 (DDR1-34K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 149 (DDR1-34H), or
variants thereof comprising a variant light chain variable region comprising an amino acid sequence at least 80% identical to the amino acid sequence of the light chain variable region, and a variant heavy chain variable region comprising an amino acid sequence at least 80% identical to the amino acid sequence of the heavy chain variable region, wherein the variant specifically binds to DDR1 protein.

7 . The monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 112 (DDR1-9K) and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 133 (DDR1-9H).

8 . The monoclonal antibody or antigen-binding fragment thereof of claim

Assignees

• Univ Texas
• Univ George Washington

Inventors

• Zhang Ningyan
• An Zhiqiang
• Deng Hui
• Sun Xiujie
• Li Rong

Classifications

• C07K16/2896 Primary

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/20

  characterized by taxonomic origin · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title