Compositions and methods for growth factor modulation
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 modulates TGF-β
- 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
), 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
, 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 a pool of antibodies, or antigen-binding portion thereof, for the ability to bind the antigen of step (i);
(iii) selecting for a pool of antibodies, or antigen-binding portions thereof, that inhibits or promotes TGF-β
signaling; and
,(iv) formulating an antibody or antigen-binding portion thereof from step (iii) into a pharmaceutical composition, wherein the antibody, or antigen-binding portion thereof is a human or humanized antibody or antigen-binding portion thereof.
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Accused Products
Abstract
Provided herein are proteins, antibodies, assays and methods useful for modulating growth factor levels and/or activities. In some embodiments, such growth factors are members of the TGF-β superfamily of proteins.
175 Citations
23 Claims
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1. A method for manufacturing a pharmaceutical composition that comprises an antibody, or an antigen-binding portion thereof, that modulates TGF-β
- 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
), 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
, 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 a pool of antibodies, or antigen-binding portion thereof, for the ability to bind the antigen of step (i); (iii) selecting for a pool of antibodies, or antigen-binding portions thereof, that inhibits or promotes TGF-β
signaling; and
,(iv) formulating an antibody or antigen-binding portion thereof from step (iii) into a pharmaceutical composition, wherein the antibody, or antigen-binding portion thereof is a human or humanized antibody or antigen-binding portion thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19, 20, 21)
- signaling, the method comprising the steps of;
-
13. The method of 1, wherein the antibody, or antigen-binding portion thereof, is an IgA, IgD, IgE, IgG or IgM antibody.
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22. A method for manufacturing a pharmaceutical composition that comprises an antibody, or an antigen-binding portion thereof, that modulates TGF-β
- 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
), 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
, 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 that comprise two cysteine residues that form disulfide bonds with the straightjacket region of the prodomains;(ii) selecting for a pool of antibodies, or antigen-binding portion thereof, for the ability to bind the antigen of step (i); (iii) selecting for a pool of antibodies, or antigen-binding portions thereof, that inhibits or promotes TGF-β
signaling; and
,(iv) formulating an antibody or antigen-binding portion thereof from step (iii) into a pharmaceutical composition, wherein the antibody, or antigen-binding portion thereof is a human or humanized antibody or antigen-binding portion thereof. - View Dependent Claims (23)
- signaling, the method comprising the steps of;
Specification