Tendon-inducing compositions
AssigneeGenetics Institute, Inc.
InventorsAnthony J. Celeste, John M. Wozney, Vicki A. Rosen, Neil M. Wolfman, Gerald H. Thomsen, Douglas A. Melton
Life of this patent
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Abstract
Compositions of proteins with tendon/ligament-like tissue inducing activity are disclosed. The compositions are useful in the treatment of tendinitis and tendon or ligament defects and in related tissue repair.
Claims28
A DNA molecule comprising an isolated DNA sequence encoding a BMP-12 related protein.
An isolated DNA molecule having a sequence encoding a BMP-12 protein which is characterized by the ability to induce the formation of tendon/ligament-like tissue, said DNA molecule comprising a DNA sequence selected from the group consisting of:
- (a) nucleotide #496, #571 or #577 to #882 of SEQ ID NO:1;
- (b) nucleotide #605 or #659 to #964 of SEQ ID NO:25;
- and
- (c) naturally occurring allelic sequences and equivalent degenerative codon sequences of (a) or (b).
A purified polypeptide comprising an amino acid sequence selected from the following group:
- (a) from amino acid #-25 to amino acid #104 as set forth in SEQ ID NO:2;
- (b) from amino acid #1 to amino acid #104 as set forth in SEQ ID NO:2.
- (c) from amino acid #3 to amino acid #104 as set forth in SEQ ID NO:2.
- (d) from amino acid #1 to amino acid #120 as set forth in SEQ ID NO:26;
- and
- (d) from amino acid #19 to amino acid #120 as set forth in SEQ ID NO:26.
A purified protein produced by the steps of
- (a) culturing a cell transformed with a DNA molecule comprising the nucleotide sequence from nucleotide #496, #571 or #577 to #882 as shown in SEQ ID NO:1;
- and
- (b) recovering and purifying from said culture medium a protein comprising the amino acid sequence from amino acid #-25, amino acid #1 or amino acid #3 to amino acid #104 as shown in SEQ ID NO:2.
A purified BMP-12 related protein characterized by the ability to induce the formation of tendon/ligament-like tissue.
A pharmaceutical composition for tendon/ligament-like tissue healing and tissue repair said composition comprising an effective amount of the protein of a BMP-12 related protein in a pharmaceutically acceptable vehicle.
A chimeric DNA molecule comprising a DNA sequence encoding a propeptide from a member of the TGF-β superfamily of proteins linked in correct reading frame to a DNA sequence encoding a BMP-12 related polypeptide.
A method for inducing tendon/ligament-like tissue formation in a patient in need of same comprising administering to said patient an effective amount of a composition comprising a protein encoded by a DNA sequence selected from the group consisting of:
- (a) nucleotides #496, #571 or #577 to #882 of SEQ ID NO:1;
- (b) nucleotides #845 or #899 to #1204 of SEQ ID NO:3;
- (c) nucleotides #605 or #659 to #964 of SEQ ID NO:25;
- and
- (d) sequences which hybridize to (a), (b) or (c) under stringent hybridization conditions and encode a protein which exhibits the ability to form tendon/ligament-like tissue.
A method for inducing tendon/ligament-like tissue formation in a patient in need of same comprising administering to said patient an effective amount of the composition comprising a tendon/ligament-like tissue inducing protein having an amino acid sequence selected from the group consisting of:
- (a) amino acids #-25, #1 or #3 to #104 of SEQ ID NO:2;
- (b) amino acids #1 or #19 to #120 of SEQ ID NO:4;
- (c) amino acids #1 or #19 to #120 of SEQ ID NO:26;
- and
- (d) mutants and/or variants of (a), (b) or (c) which exhibit the ability to form tendon and/or ligament.
A pharmaceutical composition for tendon/ligament-like tissue repair, said composition comprising an effective amount of a BMP-12 related protein in a pharmaceutically acceptable vehicle.
Dependencies are inferred from the claim text.