LAIR-1-binding agents and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12240899-B2
Application number	US-202117353295-A
Country	US
Kind code	B2
Filing date	Jun 21, 2021
Priority date	Jun 22, 2020
Publication date	Mar 4, 2025
Grant date	Mar 4, 2025

Abstract

The present disclosure provides binding agents, such as antibodies, that specifically bind LAIR-1, including human LAIR-1, as well as compositions comprising the binding agents, and methods of their use. The disclosure also provides related polynucleotides and vectors encoding the binding agents and cells comprising the binding agents.

First claim

The invention claimed is:

1. A binding agent that specifically binds the extracellular domain of human leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), wherein the binding agent comprises:
(a) a heavy chain variable region (VH) comprising a VH-complementarity determining region (CDR) 1, a VH-CDR2, and a VH-CDR3 from the amino acid sequence of SEQ ID NO: 117; and a light chain variable region (VL) comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3 from the amino acid sequence of SEQ ID NO: 118;
(b) a VH comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3 from the amino acid sequence of SEQ ID NO: 119; and a VL comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3 from the amino acid sequence of SEQ ID NO: 120;
(c) a VH comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3 from the amino acid sequence of SEQ ID NO: 115; and a VL comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3 from the amino acid sequence of SEQ ID NO: 116;
(d) a VH comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3 from the amino acid sequence of SEQ ID NO: 121; and a VL comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3 from the amino acid sequence of SEQ ID NO: 122;
(e) a VH comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3 from the amino acid sequence of SEQ ID NO: 123; and a VL comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3 from the amino acid sequence of SEQ ID NO: 124;
(f) a VH comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3 from the amino acid sequence of SEQ ID NO: 125; and a VL comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3 from the amino acid sequence of SEQ ID NO: 126;
(g) a VH comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3 from the amino acid sequence of SEQ ID NO: 127; and a VL comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3 from the amino acid sequence of SEQ ID NO: 128; or
(h) a VH comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3 from the amino acid sequence of SEQ ID NO: 129; and a VL comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3 from the amino acid sequence of SEQ ID NO: 130.

2. The binding agent of claim 1 , wherein:
(a) (1) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:25, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:26, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:27; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:28, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:30;
(2) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:31, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:32, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:27; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:28, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:30;
(3) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:25, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:33, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:27; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:28, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:30;
(4) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:34, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:26, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:27; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:28, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:30; or
(5) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:35, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:36, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:37; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:38, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:39, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:40;

(b) (1) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:25, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:41, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:27; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:28, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:42, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:30;
(2) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:31, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:43, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:27; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:28, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:42, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:30;
(3) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:25, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:27; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:28, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:42, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:30;
(4) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:34, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:41, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:27; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:28, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:42, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:30; or
(5) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:35, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:45, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:37; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:38, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:39, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:40;

(c) (1) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:9, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:11; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO:12, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:13, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:14;
(2) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:15, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:16, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:11; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 12, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO:13, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:14;
(3) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:9, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:17, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:11; and the VL comprises the VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 12, the VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and the VL-CDR3 comprising the amino acid sequence of SEQ ID NO:14;
(4) the VH comprises the VH-CDR1 comprising the amino acid sequence of SEQ ID NO:18, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and the VH-CDR3 comprising the amino acid sequence of SEQ ID NO:11; and the VL comprises the VL-CDR1

Assignees

• Ngm Biopharmaceuticals Inc

Inventors

• Crawley Suzanne Christine
• Fan Bin
• Li Betty Chan
• Rivera Lee Benjamin
• Sissons James Robert
• Sitrin Jonathan
• Wang Yan
• Zhao Xuan

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/74

  Inducing cell proliferation · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title