IP Library › Granted Patent US 12,258,391
Granted Patent B2
US 12,258,391 · App. 18/336,713 · Granted Mar 25, 2025

Anti-GDF-15 antibodies

Inventors: Lorena Lerner (Newton Centre, MA); Sandra Abbott (Boston, MA); Ailin Bai (Newton, MA); Ting Chen (Acton, MA); Maria Isabel Chiu (Newton Centre, MA); Qing Liu (Acton, MA); Laura Poling (Boston, MA); Nianjun Tao (Brighton, MA); Solly Weiler (Newton, MA); Zhigang Weng (Brookline, MA); William M. Winston, Jr. (Marlborough, MA); Jeno Gyuris (Lincoln, MA)
Assignee: AVEO Pharmaceuticals, Inc.
C07K16/22A61K39/3955A61K45/06A61P3/02A61K2039/505C07K2317/24C07K2317/76C07K2317/92C07K2319/30C12N5/10C12N15/10C12N15/63
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Quick Facts
Patent No.
US 12,258,391
App. No.
18/336,713
Granted
Mar 25, 2025
Kind
B2
Abstract

Monoclonal antibodies that bind and inhibit the activity of human GDF15 are disclosed. The antibodies can be used to treat body weight loss, including cachexia, associated with the over-expression of human GDF15.

Claims (18)

1. A method of treating cachexia in a mammal comprising administering to the mammal an effective amount of an anti-GDF15 antibody or antigen-binding fragment thereof comprising a CDR H1, a CDR H2, a CDR H3, a CDR L1, a CDR L2, and a CDR L3, wherein the CDR H1, CDR H2, and CDR H3 are found in the amino acid sequence of SEQ ID NO: 250, and wherein the CDR L1, CDR L2, and CDR L3 are found in the amino acid sequence of SEQ ID NO: 92.

2. The method of claim 1 , wherein the CDR H1 comprises the amino acid sequence of SEQ ID NO: 1, the CDR H2 comprises the amino acid sequence of SEQ ID NO: 238, the CDR H3 comprises the amino acid sequence of SEQ ID NO: 15, the CDR L1 comprises the amino acid sequence of SEQ ID NO: 21, the CDR L2 comprises the amino acid sequence of SEQ ID NO: 26, and the CDR L3 comprises the amino acid sequence of SEQ ID NO: 32.

3. The method of claim 1 , wherein the anti-GDF15 antibody comprises an immunoglobulin heavy chain variable region and an immunoglobulin light chain variable region, wherein the immunoglobulin heavy chain variable region comprises an amino acid sequence having at least 95% identity to that of SEQ ID NO: 250, and the immunoglobulin light chain variable region comprises an amino acid sequence having at least 95% identity to that of SEQ ID NO: 92.

4. The method of claim 1 , wherein loss of muscle mass associated with cachexia is inhibited.

5. The method of claim 1 , wherein involuntary weight loss associated with cachexia is inhibited or reduced.

6. The method of claim 1 , wherein loss of organ mass associated with cachexia is inhibited.

7. The method of claim 6 , wherein the cachexia is associated with an underlying disease selected from the group consisting of cancer, chronic heart failure, chronic kidney disease, COPD, AIDS, multiple sclerosis, rheumatoid arthritis, sepsis, and tuberculosis.

8. The method of claim 6 , wherein the organ is kidney, liver, heart or spleen.

9. The method of claim 6 , wherein the loss of organ mass is accompanied by a loss of muscle mass, a loss of fat mass or involuntary weight loss.

10. The method of claim 1 further comprising administering a second agent to the mammal in need thereof, wherein the second agent is selected from the group consisting of an inhibitor of Activin-A, an inhibitor of ActRIIB, an inhibitor of IL-6, an inhibitor of IL-6R, a melanocortin peptide inhibitor, a melanocortin receptor inhibitor, a ghrelin, a ghrelin mimetic, a GHS-R1a agonist, a SARM, a TNFα inhibitor, an IL-1α inhibitor, a myostatin inhibitor, a beta-blocker and an anti-cancer agent.

11. The method of claim 1 , wherein sarcopenia associated with cachexia is treated.

12. The method of claim 1 , wherein the incidence and/or severity of cachexia is decreased, thereby increasing the maximum tolerated dose of an anti-cancer agent capable of causing cachexia.

13. The method of claim 10 , wherein the antibody or antigen-binding fragment thereof is administered in combination with the anti-cancer agent.

14. The method of claim 1 , wherein the anti-GDF15 antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable region and an immunoglobulin light chain variable region, wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence of SEQ ID NO:250, and the immunoglobulin light chain variable region comprises the amino acid sequence of SEQ ID NO:92.

15. The method of claim 1 , wherein the cachexia is associated with an underlying disease selected from the group consisting of cancer, chronic heart failure, chronic kidney disease, COPD, AIDS, multiple sclerosis, rheumatoid arthritis, sepsis, and tuberculosis.

16. The method of claim 1 , wherein appetite in a mammal suffering from cachexia is increased.

17. The method of claim 4 , wherein the cachexia is associated with an underlying disease selected from the group consisting of cancer, chronic heart failure, chronic kidney disease, COPD, AIDS, multiple sclerosis, rheumatoid arthritis, sepsis, and tuberculosis.

18. The method of claim 4 , wherein the loss of muscle mass is accompanied by a loss of fat mass.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 16, 2023
From: LERNER, LORENA; ABBOTT, SANDRA; BAI, AILIN; CHEN, TING; CHIU, MARIA ISABEL; LIU, QING; POLING, LAURA; TAO, NIANJUN; WEILER, SOLLY; WENG, ZHIGANG; WINSTON, WILLIAM M.; GYURIS, JENO
To: AVEO PHARMACEUTICALS, INC.
Reel/Frame 063978/0518 →
Continuity (7)
Continuation 16824034 · Mar 19, 2020
Continuation 15655263 · Jul 20, 2017
Continuation 14863870 · Sep 24, 2015
Division 14137415 · Dec 20, 2013
Provisional Application 61827325 · May 24, 2013
Provisional Application 61745508 · Dec 21, 2012
Related Publication 20240166734A1 · May 23, 2024
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