Polynucleotides encoding human beta klotho antibodies or binding fragments thereof and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12378312-B2
Application number	US-202318153643-A
Country	US
Kind code	B2
Filing date	Jan 12, 2023
Priority date	Jan 24, 2014
Publication date	Aug 5, 2025
Grant date	Aug 5, 2025

Abstract

The present disclosure provides binding proteins, such as antibodies or binding fragments thereof, that bind beta klotho, including human beta klotho, and methods of their use such as in producing an antibody or binding fragment thereof. The present disclosure also provides vectors and cells comprising polynucleotides encoding antibodies or binding fragments thereof that bind beta klotho, including human beta klotho.

First claim

What is claimed:

1. An isolated polynucleotide or polynucleotides encoding an antibody or binding fragment thereof that binds human beta klotho, wherein the antibody or binding fragment thereof comprises
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:271; 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:276.

2. The isolated polynucleotide or polynucleotides of claim 1 , wherein:
(a) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:1, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:2, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:3, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:4, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:5, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:6;
(b) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:7, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:8, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:9, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:10, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:11, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:6;
(c) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:12, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:2, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:3, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:4, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:5, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:6;
(d) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:13, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:14, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:15, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:16, the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 11, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:17;
(e) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:18, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:19, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:20, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:21, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:22, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:23; or
(f) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:1, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:24, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:3, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:4, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:5, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:6.

3. The isolated polynucleotide or polynucleotides of claim 1 , wherein:
the VH CDR1 comprises the amino acid sequence of SEQ ID NO:12, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:2, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:3, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:4, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:5, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:6.

4. The isolated polynucleotide or polynucleotides of claim 1 , wherein
the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:271 and the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:276.

5. The isolated polynucleotide or polynucleotides of claim 1 , wherein
the VH comprises the amino acid sequence of SEQ ID NO:271 and the VL comprises the amino acid sequence of SEQ ID NO:276.

6. A vector or vectors comprising the isolated polynucleotide or polynucleotides of claim 5 .

7. A cell comprising the vector or vectors of claim 6 .

8. A method of producing an antibody or binding fragment thereof, the method comprising: (i) culturing the cell of claim 7 ; and (ii) isolating the antibody or binding fragment thereof.

9. The method of claim 8 , wherein the method further comprises formulating the antibody or binding fragment thereof as a sterile pharmaceutical formulation.

10. A cell comprising the isolated polynucleotide or polynucleotides of claim 5 .

11. The isolated polynucleotide or polynucleotides of claim 1 , wherein the antibody or binding fragment thereof is a humanized antibody.

12. The isolated polynucleotide or polynucleotides of claim 1 , wherein the antibody is a human IgG1 antibody, a human IgG2 antibody, or a human IgG4 antibody.

13. A vector or vectors comprising the isolated polynucleotide or polynucleotides of claim 1 .

14. A cell comprising the vector or vectors of claim 13 .

15. A method of producing an antibody or binding fragment thereof, the method comprising: (i) culturing the cell of claim 14 ; and (ii) isolating the antibody or binding fragment thereof.

16. The method of claim 15 , wherein the method further comprises formulating the antibody or binding fragment thereof as a sterile pharmaceutical formulation.

17. A cell comprising the isolated polynucleotide or polynucleotides of claim 1 .

18. An isolated polynucleotide or polynucleotides encoding an antibody that binds human beta klotho, wherein
the antibody comprises a heavy chain comprising amino acids 23-472 of SEQ ID NO:317 and a light chain comprising amino acids 23-240 of SEQ ID NO:319.

19. A vector or vectors comprising the isolated polynucleotide or polynucleotides of claim 18 .

20. A cell comprising the vector or vectors of claim 19 .

21. A method of producing an antibody, the method comprising: (i) culturing the cell of claim 20 ; and (ii) isolating the antibody.

22. The method of claim 21 , wherein the method further comprises formulating the antibody as a sterile pharmaceutical formulation.

23. A cell comprising the isolated polynucleotide or polynucleotides of claim 18 .

Assignees

• Ngm Biopharmaceuticals Inc

Inventors

• Mondal Kalyani
• Li Betty Chan
• Chen Yu
• Arora Taruna
• Matern Hugo
• Shen Wenyan

Classifications

• C07K16/28 Primary

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

• A61K39/001154

  Enzymes · CPC title

• G01N33/66

  involving blood sugars, e.g. galactose · CPC title

• C07K2317/75

  Agonist effect on antigen · 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