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Methods for inhibiting myostatin activation by administering anti-pro/latent myostatin antibodies

  • US 10,287,345 B2
  • Filed: 01/06/2017
  • Issued: 05/14/2019
  • Est. Priority Date: 01/08/2016
  • Status: Active Grant
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.

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