Methods of treating FGF21-associated disorders

Patent metadata

Field	Value
Publication number	US-11802152-B2
Application number	US-202117539335-A
Country	US
Kind code	B2
Filing date	Dec 1, 2021
Priority date	Aug 3, 2015
Publication date	Oct 31, 2023
Grant date	Oct 31, 2023

Abstract

The present invention relates to monoclonal antibodies and antigen-binding fragments thereof that bind to human β-klotho, and pharmaceutical compositions and methods of treatment comprising the same.

First claim

The invention claimed is:

1. A nucleic acid coding for an isolated antibody or antigen-binding fragment thereof that specifically binds to the β-klotho sequence (SEQ ID NO: 262), and said antibody or antigen-binding fragment thereof comprises one of:
(i) a heavy chain variable region comprising three heavy chain CDRs, wherein the three heavy chain CDRs comprise SEQ ID NOS: 23, 24, and 25, and a light chain variable region comprising three light chain CDRs, wherein the three light chain CDRs comprise SEQ ID NOS: 33, 34, and 35;
(ii) a heavy chain variable region comprising three heavy chain CDRs, wherein the three heavy chain CDRs comprise SEQ ID NOS: 26, 27, and 28, and a light chain variable region comprising three light chain CDRs, wherein the three light chain CDRs comprise SEQ ID NOS: 36, 37, and 38;
(iii) a heavy chain variable region comprising three heavy chain CDRs, wherein the three heavy chain CDRs comprise SEQ ID NOS: 268, 24, and 25, and a light chain variable region comprising three light chain CDRs, wherein the three light chain CDRs comprise SEQ ID NOS: 33, 34, and 35; and
(iv) a heavy chain variable region comprising three heavy chain CDRs, wherein the three heavy chain CDRs comprise SEQ ID NOS: 269, 270, and 271, and a light chain variable region comprising three light chain CDRs, wherein the three light chain CDRs comprise SEQ ID NOS: 272, 273, and 35.

2. The nucleic acid of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain sequence (VH) comprising the amino acid sequence of SEQ ID NO: 29 or an amino acid sequence with at least 80%, 90%, 95%, or 97% identity thereof; and a variable light chain sequence (VL) comprising the amino acid sequence of SEQ ID NO: 39 or an amino acid sequence with at least 80%, 90%, 95%, or 97% identity thereof.

3. The nucleic acid of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain sequence (VH) comprising the amino acid sequence of SEQ ID NO: 29 and a variable light chain sequence (VL) comprising the amino acid sequence of SEQ ID NO: 39.

4. The nucleic acid of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 31 or SEQ ID NO: 71 and a light chain comprising the amino acid sequence of SEQ ID NO: 41.

5. A vector comprising the nucleic acid according to claim 1 .

6. A host cell comprising the vector of claim 5 .

7. A method of making an antibody or antigen-binding fragment thereof which binds β-klotho, comprising the steps of:
culturing the host cell of claim 6 under conditions suitable for expression of the antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region which can be assembled; and
isolating and/or purifying said antibody or antigen-binding fragment thereof from the culture medium.

Assignees

• Novartis Ag

Inventors

• Boettcher Brian
• Caplan Shari Lynn
• Cebe Regis
• Li Guochun
• Taraszka John A
• Xu Fangmin
• Yowe David Langdon

Classifications

• A61K39/001107

  Fibroblast growth factor receptors [FGFR] · CPC title

• C07K16/28 Primary

  against receptors, cell surface antigens or cell surface determinants · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• C07K2317/24

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