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COMPOSITIONS AND METHODS FOR GROWTH FACTOR MODULATION

  • US 20200131259A1
  • Filed: 01/07/2020
  • Published: 04/30/2020
  • Est. Priority Date: 05/06/2013
  • Status: Active Application
First Claim
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1. A method for manufacturing a pharmaceutical composition that comprises an antibody, or an antigen-binding portion thereof, that inhibits TGF-β

  • 1 signaling, the method comprising the steps of;

    (i) providing an antigen comprising a protein complex that comprises;

    a) a homodimer comprising prodomains of transforming growth factor beta (TGF-β

    1), or prodomain fragments thereof that comprise a straightjacket region that includes at least one cysteine residue present within about the first 4, 5, 6 or 7 N-terminal region; and

    ,b) a protein known to associate with a pro-protein of TGF-β

    1, selected from the group consisting of;

    latent TGF-β

    binding protein 1 (LTBP1), latent TGF-β

    binding protein 3 (LTBP3), glycoprotein A repetitions predominant (GARP), leucine rich repeat containing 33 (LRRC33), and fragments or variants thereof that comprise two cysteine residues that form disulfide bonds with the straightjacket region of the prodomains, wherein the variants are at least 90% identical to a native sequence;

    (ii) selecting for one or more antibodies, or antigen-binding portions thereof, for the ability to bind the antigen of step (i) and inhibit TGF-β

    1 signaling; and

    ,(iii) expressing the antibody, or the antigen-binding portion thereof, selected in step (ii) in mammalian cells capable of large scale translation.

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