ILT-binding agents and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12410251-B2
Application number	US-202318466722-A
Country	US
Kind code	B2
Filing date	Sep 13, 2023
Priority date	May 1, 2020
Publication date	Sep 9, 2025
Grant date	Sep 9, 2025

Abstract

The present disclosure provides binding agents, such as antibodies, that specifically bind ILT2, ILT4, or both ILT2 and ILT4, 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

What is claimed:

1. A binding agent that specifically binds human immunoglobulin-like transcript 2 (ILT2) or human immunoglobulin-like transcript 4 (ILT4) comprising:
(i) 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:125; 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:126;
(ii) 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
(iii) 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 the binding agent binds human ILT2 and the VH comprises the VH-CDR1, the VH-CDR2, and the VH-CDR3 from the amino acid sequence of SEQ ID NO:125; and the VL comprises the VL-CDR1, the VL-CDR2, and the VL-CDR3 from the amino acid sequence of SEQ ID NO:126, and wherein:
(i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:31, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:23, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:24, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:25, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:26, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:27;
(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:22, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:23, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:24, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:25, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:26, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:27;
(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:28, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:29, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:24, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:25, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:26, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:27;
(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:22, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:30, the VH-CDR3 the amino acid sequence of SEQ ID NO: 24, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:25, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:26, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:27; or
(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:32, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:33, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:34, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:35, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:36, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:37.

3. The binding agent of claim 2 , wherein:
(a) the VH comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:125, and/or the VL comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:126; or
(b) the VH comprises the amino acid sequence of SEQ ID NO: 125, and/or the VL comprises the amino acid sequence of SEQ ID NO: 126.

4. The binding agent of claim 1 , wherein the binding agent binds human ILT4 and:
(a) the VH comprises the VH-CDR1, the VH-CDR2, and the VH-CDR3 from the amino acid sequence of SEQ ID NO:127; and the VL comprises the VL-CDR1, the VL-CDR2, and the VL-CDR3 from the amino acid sequence of SEQ ID NO: 128, and wherein
(i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:47, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:39, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:40, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:41, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:42, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:43;
(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:38, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:39, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:40, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:41, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:42, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:43;
(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:44, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:45, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:40, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:41, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:42, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:43;
(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:38, the VH-CDR2 comprising the amino acid sequence of SEQ ID NO:46, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:40, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:41, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:42, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:43; or
(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:48, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:49, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:50, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:51, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:52, and the VL-CDR3 comprises an amino acid sequence of SEQ ID NO:53; or

(b) the VH comprises the VH-CDR1, the VH-CDR2, and the VH-CDR3 from the amino acid sequence of SEQ ID NO: 129; and the VL comprises the VL-CDR1, the VL-CDR2, and the VL-CDR3 from the amino acid sequence of SEQ ID NO:130, and wherein
(i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:63, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:55, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:56, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:57, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:58, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:59;
(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:54, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:55, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:56, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:57, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:58, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:59;
(iii) the VH comprises the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 60, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:61, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:56, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 57, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:58, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:59;
(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:54, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:62, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:56, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:57, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO:58, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO:59; or
(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO:64, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO:65, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO:66, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO:67,

Assignees

• Ngm Biopharmaceuticals Inc

Inventors

• Duey Dana Yen Mei
• Ebens Jr Allen James
• Kaplan Daniel David
• Lam Chia-Ying Kao
• Mondal Kalyani
• Stone Geoffrey William
• Wang Yan

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

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K2317/24

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

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title