Methods of treating FGF21-associated disorders

Patent metadata

Field	Value
Publication number	US-11236159-B2
Application number	US-201615749775-A
Country	US
Kind code	B2
Filing date	Aug 2, 2016
Priority date	Aug 3, 2015
Publication date	Feb 1, 2022
Grant date	Feb 1, 2022

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. 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 isolated antibody or antigen-binding fragment thereof 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 isolated antibody or antigen-binding fragment thereof 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. A method of reducing body weight comprising administering to a human subject in need thereof a pharmaceutical composition comprising an antibody or antigen-binding fragment according to claim 3 in an amount effective to reduce body weight of the human subject.

5. A method of reducing appetite or food intake comprising administering to a human subject in need thereof a pharmaceutical composition comprising an antibody or antigen-binding fragment according to claim 3 in an amount effective to reduce appetite or food intake in the human subject.

6. A method of reducing plasma triglyceride (TG) concentrations or plasma total cholesterol (TC) concentrations in a human subject, comprising administering to the human subject in need thereof a pharmaceutical composition comprising an antibody or antigen-binding fragment according to claim 3 in an amount effective to reduce the TG concentrations or the TC concentrations in the human subject.

7. The isolated antibody or antigen-binding fragment thereof 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.

8. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

Assignees

• Novartis Ag

Inventors

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

Classifications

• C07K2318/00

  Antibody mimetics or scaffolds · CPC title

• C07K16/2863 Primary

  against receptors for growth factors, growth regulators · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P3/00

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

• A61P3/06

  Antihyperlipidemics · CPC title