IP Library › Granted Patent US 10,307,480
Granted Patent B2
US 10,307,480 · App. 15/524,651 · Granted Jun 4, 2019

Anti-pro/latent-myostatin antibodies and uses thereof

Inventors: Michelle Straub (Yarmouth, ME); Dong Yun Lee (Boston, MA); William K. McConaughy (Boston, MA); Katherine Jane Turner (Acton, MA); Nagesh K. Mahanthappa (Cambridge, MA); Justin W. Jackson (Cambridge, MA)
Assignee: Scholar Rock, Inc.
A61K39/39533A61K39/3955C07K14/475C07K16/22G01N33/53G01N33/74A61K2039/505C07K2317/21C07K2317/30C07K2317/33C07K2317/622C07K2317/76C07K2317/92G01N2800/10
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Quick Facts
Patent No.
US 10,307,480
App. No.
15/524,651
Granted
Jun 4, 2019
Kind
B2
Abstract

Aspects of the present disclosure relate to antibodies that specifically bind proMyostatin and/or latent Myostatin and uses thereof.

Claims (43)

1. An isolated antibody, or an antigen-binding fragment thereof, that specifically binds pro/latent Myostatin compared with mature Myostatin,

wherein the antibody, or antigen-binding fragment thereof, comprises six complementarity determining regions (CDRs): CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3,

wherein CDRH1 comprises a sequence that is at least 90% identical to a CDRH1 sequence as set forth as any one of SEQ ID NOs: 1, 2, 70, 71, and 77, or wherein CDRH1 comprises a sequence that is at least 90% identical to a CDRH1 sequence as set forth in any one of SEQ ID NOs: 65, 66, or 69,

wherein CDRH2 comprises a sequence that is at least 90% identical to a CDRH2 sequence as set forth as any one of SEQ ID NOs: 4, 5, 72, and 78, or wherein CDRH2 comprises a sequence that is at least 90% identical to a CDRH2 sequence as set forth in any one of SEQ ID NOs: 65, 66, 67 or 69,

wherein CDRH3 comprises a sequence that is at least 90% identical to a CDRH3 sequence as set forth as any one of SEQ ID NOs: 10, 73, 74, 75, 76, 79, and 80,

wherein CDRL1 comprises a sequence that is at least 90% identical to a CDRL1 sequence as set forth as any one of SEQ ID NOs: 12, 13, 87, 88, 89, and 98, or wherein CDRL1 comprises a sequence that is at least 90% identical to a CDRL1 sequence as set forth in any one of SEQ ID NOs: 84 or 85,

wherein CDRL2 comprises a sequence that is at least 90% identical to a CDRL2 sequence as set forth as any one of SEQ ID NOs: 18, 19, 90, 91, and 99, or wherein CDRL2 comprises a sequence that is at least 90% identical to a CDRL2 sequence as set forth in any one of SEQ ID NOs: 83, 84 or 86, and

wherein CDRL3 comprises a sequence that is at least 90% identical to a CDRL3 sequence as set forth as any one of SEQ ID NOs: 22, 93, 94, 95, 97, 100, and 101.

2. The isolated antibody, or antigen-binding fragment thereof of claim 1 , which is a fully human antibody or a humanized antibody.

3. The isolated antibody, or antigen-binding fragment thereof of claim 1 , comprising a heavy chain constant domain selected from the group consisting of: IgG, IgG1, IgG2, IgG2A, IgG2B, IgG2C, IgG3, IgG4, IgA1, IgA2, IgD, IgM, and IgE constant domains.

4. The isolated antibody, or antigen-binding fragment thereof of claim 1 , which is a monoclonal antibody or a multispecific antibody.

5. The isolated antibody, or antigen-binding fragment thereof of claim 1 , which is a diabody, a chimeric antibody, a Fab fragment, a F(ab′)2 fragment, or an Fv fragment.

6. The isolated antibody, or antigen-binding fragment thereof of claim 1 , comprising an Fc region.

7. The isolated antibody or antigen-binding fragment thereof of claim 1 , which has an equilibrium dissociation constant, Kd, of less than 10 −6 M.

8. A pharmaceutical composition comprising the isolated antibody or antigen-binding fragment thereof of claim 1 , and an excipient.

9. A pharmaceutical composition comprising the isolated antibody or antigen-binding fragment thereof of claim 1 .

10. A method of treating a myopathy or a metabolic disorder in a subject, the method comprising administering to the subject the pharmaceutical composition of claim 9 , thereby treating the myopathy or metabolic disorder.

11. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody comprises

a heavy chain variable domain comprising an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 24 and SEQ ID NO: 25, or a heavy chain domain comprising an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, and SEQ ID NO: 69, and

a light chain variable domain comprising an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 30 and SEQ ID NO: 31, or a light chain domain comprising an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, and SEQ ID NO: 86.

12. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody comprises

a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 24 and SEQ ID NO: 25, or a heavy chain domain comprising an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, and SEQ ID NO: 69, and

a light chain variable domain comprising an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 30 and SEQ ID NO: 31, or a light chain domain comprising an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, and SEQ ID NO: 86.

13. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody comprises heavy chain/light chain variable domain amino acid sequences selected from the group consisting of: SEQ ID NO: 24/SEQ ID NO: 30 and SEQ ID NO: 25/SEQ ID NO: 31, or heavy chain/light chain domain amino acid sequences selected from the group consisting of: SEQ ID NO: 64/SEQ ID NO: 81, SEQ ID NO: 65/SEQ ID NO: 82, SEQ ID NO: 66/SEQ ID NO: 83, SEQ ID NO: 67/SEQ ID NO: 84, SEQ ID NO: 68/SEQ ID NO: 85, and SEQ ID NO: 69/SEQ ID NO: 86.

14. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, binds to the pro/latent Myostatin with a decreased affinity at an acidic pH as compared to a physiological pH.

15. A method of assessing a biological sample obtained from a subject having a myopathy, the method comprising:

(a) preparing an immunological reaction mixture that comprises protein of a biological sample obtained from the subject and an antibody, or an antigen-binding fragment thereof that specifically binds latent Myostatin, wherein the antibody, or antigen-binding fragment thereof, comprises six complementarity determining regions (CDRs): CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3,

wherein CDRH1 comprises a sequence that is at least 90% identical to a CDRH1 sequence as set forth as any one of SEQ ID NOs: 1, 2, 70, 71, and 77, or wherein CDRH1 comprises a sequence that is at least 90% identical to a CDRH1 sequence as set forth in any one of SEQ ID NOs: 65, 66, or 69,

wherein CDRH2 comprises a sequence that is at least 90% identical to a CDRH2 sequence as set forth as any one of SEQ ID NOs: 4, 5, 72, and 78, or wherein CDRH2 comprises a sequence that is at least 90% identical to a CDRH2 sequence as set forth in any one of SEQ ID NOs: 65, 66, 67 or 69,

wherein CDRH3 comprises a sequence that is at least 90% identical to a CDRH3 sequence as set forth as any one of SEQ ID NOs: 10, 73, 74, 75, 76, 79, and 80,

wherein CDRL1 comprises a sequence that is at least 90% identical to a CDRL1 sequence as set forth as any one of SEQ ID NOs: 12, 13, 87, 88, 89, and 98, or wherein CDRL1 comprises a sequence that is at least 90% identical to a CDRL1 sequence as set forth in any one of SEQ ID NOs: 84 or 85,

wherein CDRL2 comprises a sequence that is at least 90% identical to a CDRL2 sequence as set forth as any one of SEQ ID NOs: 18, 19, 90, 91, and 99, or wherein CDRL2 comprises a sequence that is at least 90% identical to a CDRL2 sequence as set forth in any one of SEQ ID NOs: 83, 84 or 86, and

wherein CDRL3 comprises a sequence that is at least 90% identical to a CDRL3 sequence as set forth as any one of SEQ ID NOs: 22, 93, 94, 95, 97, 100, and 101;

(b) maintaining the immunological reaction mixture under conditions that permit binding complexes to form between the antibody and a latent Myostatin; and

(c) determining the extent of binding complex formation.

16. The method of claim 15 , wherein the antibody comprises

a heavy chain variable domain comprising an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 24 and SEQ ID NO: 25, or a heavy chain domain comprising an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, and SEQ ID NO: 69, and

a light chain variable domain comprising an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 30 and SEQ ID NO: 31, or a light chain domain comprising an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, and SEQ ID NO: 86.

17. The method of claim 16 , wherein the antibody comprises

a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 24 and SEQ ID NO: 25, or a heavy chain domain comprising an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, and SEQ ID NO: 69, and

a light chain variable domain comprising an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 30 and SEQ ID NO: 31, or a light chain domain comprising an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, and SEQ ID NO: 86.

18. The method of claim 15 , wherein the antibody comprises heavy chain/light chain variable domain amino acid sequences selected from the group consisting of: SEQ ID NO: 24/SEQ ID NO: 30 and SEQ ID NO: 25/SEQ ID NO: 31, or heavy chain/light chain domain amino acid sequences selected from the group consisting of: SEQ ID NO: 64/SEQ ID NO: 81, SEQ ID NO: 65/SEQ ID NO: 82, SEQ ID NO: 66/SEQ ID NO: 83, SEQ ID NO: 67/SEQ ID NO: 84, SEQ ID NO: 68/SEQ ID NO: 85, and SEQ ID NO: 69/SEQ ID NO: 86.

19. The method of claim 15 , wherein the antibody, or antigen-binding fragment thereof, binds to the pro/latent Myostatin with a decreased affinity at an acidic pH as compared to a physiological pH.

Assignments (3)
SECURITY INTEREST Recorded Mar 3, 2026
From: SCHOLAR ROCK, INC.
To: LSI FINANCING LLC, AS ADMINISTRATIVE AGENT
Reel/Frame 075015/0854 →
CHANGE OF ASSIGNEE ADDRESS Recorded Sep 16, 2025
From: SCHOLAR ROCK, INC.
To: SCHOLAR ROCK, INC.
Reel/Frame 072878/0561 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 6, 2017
From: STRAUB, MICHELLE; LEE, DONG YUN; MCCONAUGHY, WILLIAM K.; SHEEHAN, JARED J.; TURNER, KATHERINE JANE; MAHANTHAPPA, NAGESH K.; CARVEN, GREGORY J.; JACKSON, JUSTIN W.
To: SCHOLAR ROCK, INC.
Reel/Frame 042920/0975 →
Continuity (5)
Provisional Application 62219094 · Sep 15, 2015
Provisional Application 62187348 · Jul 1, 2015
Provisional Application 62100361 · Jan 6, 2015
Provisional Application 62076230 · Nov 6, 2014
Related Publication 20170333558A1 · Nov 23, 2017
Cited By (3)
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