Anti-myostatin antibodies, polypeptides containing variant Fc regions, and methods of use

Patent metadata

Field	Value
Publication number	US-11454633-B2
Application number	US-202016889066-A
Country	US
Kind code	B2
Filing date	Jun 1, 2020
Priority date	Dec 19, 2014
Publication date	Sep 27, 2022
Grant date	Sep 27, 2022

Abstract

The disclosure provides anti-myostatin antibodies and methods of making and using the same. Nucleic acids encoding the anti-myostatin antibodies and host cells comprising the nucleic acids are also provided. The anti-myostatin antibodies have uses that include treating a muscle wasting disease, reducing body fat accumulation, and increasing mass and strength of muscle tissue. The disclosure also provides polypeptides containing a variant Fc region and methods of making and using the same. Nucleic acids encoding the polypeptides and host cells comprising the nucleic acids are also provided. The polypeptides have uses that include suppressing the activation of immune cells; treating an immunological inflammatory disease, autoimmune disease, or viral infection; and increasing muscle mass and strength or reducing body fat accumulation.

First claim

What is claimed is:

1. A method of treating an individual having a muscle wasting disease comprising administering to the individual an effective amount of an antibody that binds to latent myostatin; wherein the antibody comprises:
(a) a HVR-H1 comprising the amino acid sequence X 1 X 2 DIS (SEQ ID NO: 126), wherein X 1 is S or H, X 2 is Y, T, D or E;
(b) a HVR-H2 comprising the amino acid sequence IISX 1 AGX 2 X 3 YX 4 X 5 X 6 WAKX 7 (SEQ ID NO: 127), wherein X 1 is Y or H, X 2 is S or K, X 3 is T, M or K, X 4 is Y or K, X 5 is A, M or E, X 6 is S or E, X 7 is G or K;
(c) a HVR-H3 comprising the amino acid sequence GVPAX 1 SX 2 GGDX 3 (SEQ ID NO: 128, wherein X 1 is Y or H, X 2 is T or H, X 3 is L or K;
(d) a HVR-L1 comprising the amino acid sequence X 1 X 2 SQX 3 VX 4 X 5 X 6 NWLS (SEQ ID NO: 129), wherein X 1 is Q or T, X 2 is S or T, X 3 is S or E, X 4 is Y or F, X 5 is D or H, X 6 is N, D, A or E;
(e) a HVR-L2 comprising the amino acid sequence WAX 1 TLAX 2 (SEQ ID NO: 130), wherein X 1 is S or E, X 2 is S, Y, F or W; and
(f) a HVR-L3 comprising the amino acid sequence AGGYGGGX 1 YA (SEQ ID NO: 131), wherein X 1 is L or R.

2. The method of claim 1 , wherein the antibody comprises:
(a) a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 114;
(b) a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 58;
(c) a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 63;
(d) a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 123;
(e) a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71; and
(f) a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 74.

3. The method of claim 1 , wherein the antibody comprises:
(a) a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 114;
(b) a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 58;
(c) a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 63;
(d) a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122;
(e) a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71; and
(f) a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 74.

4. The method of claim 1 , wherein the antibody comprises:
(a) a VH sequence of SEQ ID NO: 13, 16-30, 32-34, 86-94, or 95; and
(b) a VL sequence of SEQ ID NO:15, 31, 35-38, 96-98, or 99.

5. The method of claim 1 , wherein the antibody comprises a VH and VL pair selected from the group consisting of:
(a) a VH of SEQ ID NO: 87 and a VL of SEQ ID NO: 96;
(b) a VH of SEQ ID NO: 88 and a VL of SEQ ID NO: 96;
(c) a VH of SEQ ID NO: 89 and a VL of SEQ ID NO: 96;
(d) a VH of SEQ ID NO: 90 and a VL of SEQ ID NO: 96;
(e) a VH of SEQ ID NO: 91 and a VL of SEQ ID NO: 96;
(f) a VH of SEQ ID NO: 93 and a VL of SEQ ID NO: 97;
(g) a VH of SEQ ID NO: 94 and a VL of SEQ ID NO: 97;
(h) a VH of SEQ ID NO: 86 and a VL of SEQ ID NO: 98; and
(i) a VH of SEQ ID NO: 95 and a VL of SEQ ID NO: 97.

6. The method of claim 1 , wherein the antibody comprises a VH of SEQ ID NO: 86 and a VL of SEQ ID NO: 96.

7. The method of claim 1 , wherein the antibody comprises a VH of SEQ ID NO: 92 and a VL of SEQ ID NO: 97.

8. The method of claim 1 , wherein the antibody is a full length IgG antibody.

9. The method of claim 8 , wherein the IgG antibody is IgG1, IgG2, IgG3 or IgG4.

10. The antibody of claim 9 , wherein the IgG antibody is IgG1.

11. The antibody of claim 8 , which comprises a variant Fc region amino acid sequence of SEQ ID NO: 229-380, or 381.

12. The method of claim 2 , wherein the antibody is a full length IgG antibody.

13. The method of claim 12 , wherein the IgG antibody is IgG1, IgG2, IgG3 or IgG4.

14. The antibody of claim 13 , wherein the IgG antibody is IgG 1.

15. The antibody of claim 12 , which comprises a variant Fc region amino acid sequence of SEQ ID NO: 229-380, or 381.

16. The method of claim 7 , wherein the antibody is a full length IgG antibody.

17. The method of claim 16 , wherein the IgG antibody is IgG1, IgG2, IgG3 or IgG4.

18. The antibody of claim 17 , wherein the IgG antibody is IgG 1.

19. The antibody of claim 16 , which comprises a variant Fc region amino acid sequence of SEQ ID NO: 229-380, or 381.

Assignees

• Chugai Pharmaceutical Co Ltd

Inventors

• Ruike Yoshinao
• Kuramochi Taichi
• Muramatsu Hiroyasu
• Ueyama Atsunori
• Igawa Tomoyuki
• Katada Hitoshi
• Hori Yuji

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P21/02

  Muscle relaxants, e.g. for tetanus or cramps · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• C07K16/22 Primary

  against growth factors {; against growth regulators} · CPC title