Celtrix Pharmaceuticals, Inc.

David K Schmidt

Yasushi Ogawa

Rosa Armstrong

Ranga Nathan

Andrea Y Thompson

Saeid M Seyedin

James R Dasch

The invention relates to peptides corresponding to regions of the amino acid sequence of TGF-.beta.1 or TGF-.beta.2 which retain, either in monomeric or polymeric forms, at least some of the biological activity of the respective full length TGF-.beta.. The monomeric form of the peptide derived from TGF-.beta.1 comprises the following amino acid sequence: CVRQLYIDFRKDLGWKWIHEPKGYHANFCLGP (SEQ ID NO: 1). The monomeric form of the peptide derived from TGF-.beta.2 comprises the following amino acid sequence: CLRPLYIDFKRDLGWKWIHEPKGYNANFCAGA (SEQ ID NO: 2). Dimers may be formed via disulfide bonds between the amino-terminal cysteine residues, the carboxy-terminal cysteine residues, or amino- and carboxy-terminal cysteine residues of the monomer subunits.

Biologically active TGF-.beta.1 peptides

A heterodimeric form of TGF-.beta. is described. This 25 KD molecule is active in an in vitro assay of inhibition of epithelial cell growth. The protein may be isolated from bone. When reduced, the protein elutes in two peaks by RP-HPLC. In immunoblots, the reduced protein from the earlier eluting peak reacts predominately with antibodies directed against TGF-.beta.3, while reduced protein from the later eluting peak reacts predominately with antibodies directed against TGF-.beta.2. The N-terminal amino acid sequence and immunoreactivity of the native protein are consistent with a heterodimer of TGF-.beta.2 and TGF-.beta.3.

Transforming growth factor .beta.2,3

Biologically active TGF-.beta.2 peptides

Activin is administered systemically and locally to induce the growth of mature bone. Activin enhances the level of bone formation and the quality of the bone formed when administered locally with BMP or bone marrow. Administration of activin by subcutaneous route promotes systemic increase in the bone mass.

Method and activin compositions for inducing bone growth

Method for inducing bone growth

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Santa Cruz, CA, United States of America

David K Schmidt