Anti-chemokine like receptor 1 humanized antibodies and their therapeutic applications

Patent metadata

Field	Value
Publication number	US-12534533-B2
Application number	US-202017767606-A
Country	US
Kind code	B2
Filing date	Oct 9, 2020
Priority date	Oct 9, 2019
Publication date	Jan 27, 2026
Grant date	Jan 27, 2026

Abstract

The present invention provides humanized anti-CMKLR1 compounds having an agonist capability on the interaction between Resolvin E1 and CMKLR1, and their uses for treating or preventing a disease, in particular wherein the resolution of inflammation is delayed or disrupted.

First claim

The invention claimed is:

1 . An anti-Chemerin Like Receptor 1 (CMKLR1) antibody or antigen-binding fragment thereof which binds to CMKLR1, said antibody or antigen-binding fragment thereof comprising:
a. a heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 91 and a light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 93; or b. a VH domain comprising the amino acid sequence of SEQ ID NO: 91 and a VL domain comprising the amino acid sequence of SEQ ID NO: 55.

2 . The anti-CMKLR1 antibody or antigen-binding fragment thereof according to claim 1 wherein the antibody or antigen-binding fragment thereof binds specifically to the third extra-cellular loop (EL3) of CMKLR1.

3 . The anti-CMKLR1 antibody or antigen-binding fragment thereof according to claim 1 wherein the antibody or antigen-binding fragment thereof binds specifically an epitope located within the polypeptide comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 59 or to an epitope located within the amino acid sequence of SEQ ID NO: 60.

4 . The anti-CMKLR1 antibody or antigen-binding fragment thereof according to claim 1 , which is a Resolvin E1-like agonist of CMKLR1.

5 . The anti-CMKLR1 antibody or antigen-binding fragment thereof according to claim 1 , which comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 91 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 93.

6 . The anti-CMKLR1 antibody or antigen-binding fragment according to claim 5 , wherein the light chain constant domain comprises the sequence of SEQ ID NO: 79, and wherein the antibody heavy chain constant domain is derived from a human IgG1, IgG2, IgG3, or IgG4 heavy chain constant domain.

7 . The anti-CMKLR1 antibody or antigen-binding fragment according to claim 5 , wherein the antibody heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84.

8 . The anti-CMKLR1 antibody or antigen-binding fragment according to claim 5 , wherein the antibody heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 80 or SEQ ID NO: 83.

9 . A method for treating an inflammatory disease, an autoimmune disease or a cancer in a subject in need thereof, the method comprising administering to said subject an effective amount of anti-CMKLR1 antibody or antigen-binding fragment thereof according to claim 5 .

10 . The method according to claim 9 , wherein said inflammatory disease is selected from NASH, scleroderma, cystic fibrosis, and ANCA.

11 . The anti-CMKLR1 antibody or antigen-binding fragment thereof according to claim 1 , which does not activate the beta-arrestin signaling pathway in CMKLR1-positive cells in vitro or in vivo.

12 . The anti-CMKLR1 antibody or antigen-binding fragment thereof according to claim 1 , which does not exhibit a depletion of CMKLR1-positive cells in vitro and/or in vivo.

13 . The anti-CMKLR1 antibody or antigen-binding fragment thereof according to claim 1 , which does not compete with Chemerin for the binding to CMKLR1 or which does not interfere with the binding of Chemerin to CMKLR1.

14 . The anti-CMKLR1 antibody or antigen-binding fragment according to claim 1 which is a humanized monoclonal antibody or antigen-binding fragment thereof.

15 . The anti-CMKLR1 antibody or antigen-binding fragment according to claim 14 wherein the antibody light chain constant domain is derived from a human kappa light chain constant domain.

16 . The anti-CMKLR1 antibody or antigen-binding fragment according to claim 14 wherein the light chain constant domain comprises the sequence of SEQ ID NO: 79, and wherein the antibody heavy chain constant domain is derived from a human IgG1, IgG2, IgG3, or IgG4 heavy chain constant domain.

17 . The anti-CMKLR1 antibody or antigen-binding fragment according to claim 14 , wherein the antibody heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84.

18 . The anti-CMKLR1 antibody or antigen-binding fragment according to claim 14 wherein the antibody heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 80 or SEQ ID NO: 83.

19 . A method for treating an inflammatory disease, an autoimmune disease or a cancer in a subject in need thereof, the method comprising administering to said subject an effective amount of the anti-CMKLR1 antibody or antigen-binding fragment thereof according to claim 1 .

20 . The method according to claim 19 , wherein said inflammatory disease is selected from NASH (Nonalcoholic steatohepatitis), scleroderma, cystic fibrosis, and anti-neutrophil cytoplasm antibodies-related disease (ANCA).

Assignees

• Ose Immunotherapeutics

Inventors

• Gauttier Vanessa
• Poirier Nicolas
• Mary Caroline
• Trilleaud Charlene

Classifications

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• A61K2039/505

  comprising antibodies · CPC title