Methods for inhibiting myostatin activation by administering anti-pro/latent myostatin antibodies
First Claim
Patent Images
1. A method for inhibiting myostatin activation in a subject, the method comprising a step of:
- administering to the subject a composition comprising an antibody, or antigen binding fragment thereof, that specifically binds pro-myostatin and latent myostatin and blocks release of mature myostatin, in an amount effective to cause two or more of the following in the subject;
(a) an increase in mass and/or function of a muscle tissue in the subject;
(b) a decrease in ratio of adipose-to-muscle tissue in the subject;
(c) a decrease in intramuscular fat infiltration in the subject; and
(d) prevention of muscle loss or atrophy in the subject;
wherein the subject is a human subject that benefits from reduced myostatin signaling;
wherein the amount is an amount that causes an increase in a level of circulating latent myostatin in a serum sample, as compared to a control; and
,wherein the antibody, or antigen binding fragment thereof, comprises any one of the following;
i) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
24 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
30;
ii) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to SEQ ID NO;
1, a CDRH2 sequence that is at least 90% identical to SEQ ID NO;
4, and a CDRH3 sequence that is at least 90% identical to SEQ ID NO;
10, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to SEQ ID NO;
12, a CDRL2 sequence that is at least 90% identical to SEQ ID NO;
18, and a CDRL3 sequence that is at least 90% identical to SEQ ID NO;
22;
iii) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
25 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
31;
iv) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
26 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
32;
v) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to SEQ ID NO;
1, a CDRH2 sequence that is at least 90% identical to SEQ ID NO;
6, and a CDRH3 sequence that is at least 90% identical to SEQ ID NO;
11, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to SEQ ID NO;
14, a CDRL2 sequence that is at least 90% identical to SEQ ID NO;
20, and a CDRL3 sequence that is at least 90% identical to SEQ ID NO;
23;
vi) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
27 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
33;
vii) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
28 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
34;
viii) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to SEQ ID NO;
1, a CDRH2 sequence that is at least 90% identical to SEQ ID NO;
8, and a CDRH3 sequence that is at least 90% identical to SEQ ID NO;
11, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to SEQ ID NO;
16, a CDRL2 sequence that is at least 90% identical to SEQ ID NO;
20, and a CDRL3 sequence that is at least 90% identical to SEQ ID NO;
23;
ix) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
29 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
35;
x) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to a CDRH1 sequence of SEQ ID NO;
29, a CDRH2 sequence that is at least 90% identical to a CDRH2 sequence of SEQ ID NO;
29, and a CDRH3 sequence that is at least 90% identical to a CDRH3 sequence of SEQ ID NO;
29, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to a CDRL1 sequence of SEQ ID NO;
35, a CDRL2 sequence that is at least 90% identical to a CDRL2 sequence of SEQ ID NO;
35, and a CDRL3 sequence that is at least 90% identical to a CDRL3 sequence of SEQ ID NO;
35;
xi) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
73 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
74;
xii) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to a CDRH1 sequence of SEQ ID NO;
73, a CDRH2 sequence that is at least 90% identical to a CDRH2 sequence of SEQ ID NO;
73, and a CDRH3 sequence that is at least 90% identical to a CDRH3 sequence of SEQ ID NO;
73, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to a CDRL1 sequence of SEQ ID NO;
74, a CDRL2 sequence that is at least 90% identical to a CDRL2 sequence of SEQ ID NO;
74, and a CDRL3 sequence that is at least 90% identical to a CDRL3 sequence of SEQ ID NO;
74;
xiii) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
78 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
79;
xiv) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to a CDRH1 sequence of SEQ ID NO;
78, a CDRH2 sequence that is at least 90% identical to a CDRH2 sequence of SEQ ID NO;
78, and a CDRH3 sequence that is at least 90% identical to a CDRH3 sequence of SEQ ID NO;
78, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to a CDRL1 sequence of SEQ ID NO;
79, a CDRL2 sequence that is at least 90% identical to a CDRL2 sequence of SEQ ID NO;
79, and a CDRL3 sequence that is at least 90% identical to a CDRL3 sequence of SEQ ID NO;
79;
xv) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
83 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
84;
orxvi) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to a CDRH1 sequence of SEQ ID NO;
83, a CDRH2 sequence that is at least 90% identical to a CDRH2 sequence of SEQ ID NO;
83, and a CDRH3 sequence that is at least 90% identical to a CDRH3 sequence of SEQ ID NO;
83, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to a CDRL1 sequence of SEQ ID NO;
84, a CDRL2 sequence that is at least 90% identical to a CDRL2 sequence of SEQ ID NO;
84, and a CDRL3 sequence that is at least 90% identical to a CDRL3 sequence of SEQ ID NO;
84.
1 Assignment
0 Petitions
Accused Products
Abstract
The present invention relates to antibodies that specifically bind pro-myostatin and/or latent myostatin, and methods and uses thereof.
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Citations
11 Claims
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1. A method for inhibiting myostatin activation in a subject, the method comprising a step of:
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administering to the subject a composition comprising an antibody, or antigen binding fragment thereof, that specifically binds pro-myostatin and latent myostatin and blocks release of mature myostatin, in an amount effective to cause two or more of the following in the subject; (a) an increase in mass and/or function of a muscle tissue in the subject; (b) a decrease in ratio of adipose-to-muscle tissue in the subject; (c) a decrease in intramuscular fat infiltration in the subject; and (d) prevention of muscle loss or atrophy in the subject; wherein the subject is a human subject that benefits from reduced myostatin signaling; wherein the amount is an amount that causes an increase in a level of circulating latent myostatin in a serum sample, as compared to a control; and
,wherein the antibody, or antigen binding fragment thereof, comprises any one of the following; i) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
24 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
30;ii) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to SEQ ID NO;
1, a CDRH2 sequence that is at least 90% identical to SEQ ID NO;
4, and a CDRH3 sequence that is at least 90% identical to SEQ ID NO;
10, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to SEQ ID NO;
12, a CDRL2 sequence that is at least 90% identical to SEQ ID NO;
18, and a CDRL3 sequence that is at least 90% identical to SEQ ID NO;
22;iii) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
25 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
31;iv) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
26 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
32;v) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to SEQ ID NO;
1, a CDRH2 sequence that is at least 90% identical to SEQ ID NO;
6, and a CDRH3 sequence that is at least 90% identical to SEQ ID NO;
11, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to SEQ ID NO;
14, a CDRL2 sequence that is at least 90% identical to SEQ ID NO;
20, and a CDRL3 sequence that is at least 90% identical to SEQ ID NO;
23;vi) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
27 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
33;vii) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
28 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
34;viii) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to SEQ ID NO;
1, a CDRH2 sequence that is at least 90% identical to SEQ ID NO;
8, and a CDRH3 sequence that is at least 90% identical to SEQ ID NO;
11, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to SEQ ID NO;
16, a CDRL2 sequence that is at least 90% identical to SEQ ID NO;
20, and a CDRL3 sequence that is at least 90% identical to SEQ ID NO;
23;ix) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
29 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
35;x) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to a CDRH1 sequence of SEQ ID NO;
29, a CDRH2 sequence that is at least 90% identical to a CDRH2 sequence of SEQ ID NO;
29, and a CDRH3 sequence that is at least 90% identical to a CDRH3 sequence of SEQ ID NO;
29, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to a CDRL1 sequence of SEQ ID NO;
35, a CDRL2 sequence that is at least 90% identical to a CDRL2 sequence of SEQ ID NO;
35, and a CDRL3 sequence that is at least 90% identical to a CDRL3 sequence of SEQ ID NO;
35;xi) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
73 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
74;xii) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to a CDRH1 sequence of SEQ ID NO;
73, a CDRH2 sequence that is at least 90% identical to a CDRH2 sequence of SEQ ID NO;
73, and a CDRH3 sequence that is at least 90% identical to a CDRH3 sequence of SEQ ID NO;
73, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to a CDRL1 sequence of SEQ ID NO;
74, a CDRL2 sequence that is at least 90% identical to a CDRL2 sequence of SEQ ID NO;
74, and a CDRL3 sequence that is at least 90% identical to a CDRL3 sequence of SEQ ID NO;
74;xiii) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
78 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
79;xiv) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to a CDRH1 sequence of SEQ ID NO;
78, a CDRH2 sequence that is at least 90% identical to a CDRH2 sequence of SEQ ID NO;
78, and a CDRH3 sequence that is at least 90% identical to a CDRH3 sequence of SEQ ID NO;
78, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to a CDRL1 sequence of SEQ ID NO;
79, a CDRL2 sequence that is at least 90% identical to a CDRL2 sequence of SEQ ID NO;
79, and a CDRL3 sequence that is at least 90% identical to a CDRL3 sequence of SEQ ID NO;
79;xv) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO;
83 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO;
84;
orxvi) a heavy chain variable region sequence comprising a CDRH1 sequence that is at least 90% identical to a CDRH1 sequence of SEQ ID NO;
83, a CDRH2 sequence that is at least 90% identical to a CDRH2 sequence of SEQ ID NO;
83, and a CDRH3 sequence that is at least 90% identical to a CDRH3 sequence of SEQ ID NO;
83, and a light chain variable region sequence comprising a CDRL1 sequence that is at least 90% identical to a CDRL1 sequence of SEQ ID NO;
84, a CDRL2 sequence that is at least 90% identical to a CDRL2 sequence of SEQ ID NO;
84, and a CDRL3 sequence that is at least 90% identical to a CDRL3 sequence of SEQ ID NO;
84. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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Specification