Antibody or fragment thereof that binds to fcrl1

Patent metadata

Field	Value
Publication number	US-2025382371-A1
Application number	US-202318836859-A
Country	US
Kind code	A1
Filing date	Feb 9, 2023
Priority date	Feb 9, 2022
Publication date	Dec 18, 2025
Grant date	—

Abstract

The present invention relates to a monoclonal antibody or an antibody fragment thereof that binds to an extracellular region of FCRL1, a hybridoma that produces the antibody, a nucleic acid comprising a nucleotide sequence that encodes the antibody or the antibody fragment thereof, a cell transformed with a vector comprising the nucleic acid, a method for producing the antibody or the antibody fragment thereof using the hybridoma or the transformed cell, an antibody-drug conjugate comprising the antibody or the antibody fragment thereof, a therapeutic agent and a diagnostic agent, each of which comprises the antibody or the antibody fragment thereof, and a therapeutic method and a diagnostic method for a disease associated with FCRL1 using the antibody, the antibody fragment thereof, or the antibody-drug conjugate comprising the antibody or the antibody fragment thereof.

First claim

1 . An antibody or an antibody fragment thereof, which is a monoclonal antibody or an antibody fragment thereof that binds to Fc receptor-like protein 1 (hereinafter, abbreviated as FCRL1), wherein the antibody is any one antibody selected from the following (a) to (g):
(a) an antibody in which complementarity determining regions (hereinafter, abbreviated as CDR) 1 to 3 of a heavy chain variable region (hereinafter, abbreviated as VH) comprise the amino acid sequences represented by SEQ ID NOs: 20 to 22, respectively, and CDRs 1 to 3 of a light chain variable region (hereinafter, abbreviated as VL) comprise the amino acid sequences represented by SEQ ID NOs: 24 to 26, respectively, (b) an antibody in which CDRs 1 to 3 of a VH comprise the amino acid sequences represented by SEQ ID NOs: 28 to 30, respectively, and CDRs 1 to 3 of a VL comprise the amino acid sequences represented by SEQ ID NOs: 32 to 34, respectively, (c) an antibody in which CDRs 1 to 3 of a VH comprise the amino acid sequences represented by SEQ ID NOs: 36 to 38, respectively, and CDRs 1 to 3 of a VL comprise the amino acid sequences represented by SEQ ID NOs: 40 to 42, respectively, (d) an antibody in which CDRs 1 to 3 of a VH comprise the amino acid sequences represented by SEQ ID NOs: 44 to 46, respectively, and CDRs 1 to 3 of a VL comprise the amino acid sequences represented by SEQ ID NOs: 48 to 50, respectively, (e) an antibody in which CDRs 1 to 3 of a VH comprise the amino acid sequences represented by SEQ ID NOs: 52 to 54, respectively, and CDRs 1 to 3 of a VL comprise the amino acid sequences represented by SEQ ID NOs: 56 to 58, respectively, and (f) an antibody in which CDRs 1 to 3 of a VH comprise the amino acid sequences represented by SEQ ID NOs: 60 to 62, respectively, and CDRs 1 to 3 of a VL comprise the amino acid sequences represented by SEQ ID NOs: 64 to 66, respectively, and (g) an antibody in which CDRs 1 to 3 of a VH comprise the amino acid sequences represented by SEQ ID NOs: 36 to 38, respectively, and CDRs 1 to 3 of a VL comprise the amino acid sequences represented by SEQ ID NOs: 40, 71, and 42, respectively.

2 . An antibody or an antibody fragment thereof, which is a monoclonal antibody or an antibody fragment thereof that binds to FCRL1, wherein the antibody is any one antibody selected from the following (2b-1) to (2b-4), (2c-1), (2c-2), and (2g-1):
(2b-1) an antibody in which a VH comprises the amino acid sequence represented by SEQ ID NO: 72 and a VL comprises the amino acid sequence represented by SEQ ID NO: 68, (2b-2) an antibody in which a VH comprises the amino acid sequence represented by SEQ ID NO: 73 and a VL comprises the amino acid sequence represented by SEQ ID NO: 74, (2b-3) an antibody in which a VH comprises the amino acid sequence represented by SEQ ID NO: 72 and a VL comprises the amino acid sequence represented by SEQ ID NO: 74, (2b-4) an antibody in which a VH comprises the amino acid sequence represented by SEQ ID NO: 73 and a VL comprises the amino acid sequence represented by SEQ ID NO: 68, (2c-1) an antibody in which a VH comprises the amino acid sequence represented by SEQ ID NO: 75 and a VL comprises the amino acid sequence represented by SEQ ID NO: 76, (2c-2) an antibody in which a VH comprises the amino acid sequence represented by SEQ ID NO: 77 and a VL comprises the amino acid sequence represented by SEQ ID NO: 76, and (2g-1) an antibody in which a VH comprises the amino acid sequence represented by SEQ ID NO: 77 and a VL comprises the amino acid sequence represented by SEQ ID NO: 78.

3 . The antibody or the antibody fragment thereof according to claim 1 or 2 , wherein a heavy chain constant region of the antibody is a heavy chain constant region of IgG.

4 . The antibody or the antibody fragment thereof according to claim 3 , wherein the heavy chain constant region of the antibody comprises the amino acid sequence represented by SEQ ID NO: 79 or 80.

5 . The antibody or the antibody fragment thereof according to any one of claims 1 to 4 , wherein the antibody is a genetically recombinant antibody.

6 . The antibody or the antibody fragment thereof according to claim 5 , wherein the genetically recombinant antibody is one selected from the group consisting of a chimeric antibody, a humanized antibody, and a human antibody.

7 . The antibody fragment according to any one of claims 1 to 6 , wherein the antibody fragment is one selected from Fab, Fab′, F(ab′) 2 , a single chain antibody (scFv), a dimerized V region (diabody), a disulfide-stabilized V region (dsFv), and a peptide comprising a CDR.

8 . A hybridoma that produces the antibody according to any one of claims 1 to 6 .

9 . A nucleic acid comprising a nucleotide sequence that encodes the antibody or the antibody fragment thereof according to any one of claims 1 to 7 .

10 . A vector comprising the nucleic acid according to claim 9 .

11 . A transformed cell obtained by introducing the vector according to claim 10 into a host cell.

12 . A method for producing the antibody or the antibody fragment thereof according to any one of claims 1 to 7 , comprising:
culturing the hybridoma according to claim 8 or the transformed cell according to claim 11 in a medium, and collecting the antibody or the antibody fragment thereof from a culture.

13 . An antibody-drug conjugate comprising:
the antibody or the antibody fragment thereof according to any one of claims 1 to 7 .

14 . The antibody-drug conjugate according to claim 13 , wherein the antibody-drug conjugate comprises the antibody or the antibody fragment thereof linked to a drug via a linker.

15 . A composition comprising:
the antibody or the antibody fragment thereof according to any one of claims 1 to 7 , or the antibody-drug conjugate according to claim 13 or 14 .

16 . A reagent for detecting or measuring FCRL1, comprising:
the antibody or the antibody fragment thereof according to any one of claims 1 to 7 , or the antibody-drug conjugate according to claim 13 or 14 .

17 . A diagnostic agent for a disease associated with FCRL1, comprising:
the antibody or the antibody fragment thereof according to any one of claims 1 to 7 , or the antibody-drug conjugate according to claim 13 or 14 .

18 . The diagnostic agent according to claim 17 , wherein the disease associated with FCRL1 is cancer, an autoimmune disease or an inflammatory disease.

19 . A therapeutic agent for a disease associated with FCRL1, comprising:
the antibody or the antibody fragment thereof according to any one of claims 1 to 7 , or the antibody-drug conjugate according to claim 13 or 14 .

20 . The therapeutic agent according to claim 19 , wherein the disease associated with FCRL1 is cancer, an autoimmune disease, or an inflammatory disease.

21 . A diagnostic method for a disease associated with FCRL1, comprising:
using the antibody or the antibody fragment thereof according to any one of claims 1 to 7 , or the antibody-drug conjugate according to claim 13 or 14 .

22 . A therapeutic method for a disease associated with FCRL1, comprising:
administering the antibody or the antibody fragment thereof according to any one of claims 1 to 7 , or the antibody-drug conjugate according to claim 13 or 14 .

23 . Use of the antibody or the antibody fragment thereof according to any one of claims 1 to 7 , or the antibody-drug conjugate according to claim 13 or 14 , for manufacturing a diagnostic agent for a disease a

Assignees

• Nat Inst Biomedical Innovation Health & Nutrition
• Kyowa Kirin Co Ltd

Inventors

• Nagata Satoshi
• Ise Tomoko
• KAMADA Haruhiko
• Sato Hidetaka
• Tokunaga Akihiro
• Matsubara Masahiro
• Namisaki Hiroshi
• YAMADA Takenao

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• C12N5/12

  Fused cells, e.g. hybridomas · CPC title

• C07K2317/77

  Internalization into the cell · 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