DNA sequences encoding novel growth/differentiation factors

Abstract

The invention provides DNA sequences encoding novel members of the TGF-β family of proteins. The. TGF-β family comprises proteins which function as growth and/or differentiation factors and which are useful in medical applications. Accordingly, the invention also describes the isolation of the above-mentioned DNA sequences, the expression of the encoded proteins, the production of said proteins and pharmaceutical compositions containing said proteins.

1 . A method for the treatment of bone, cartilage or tooth defects and/or for wound healing and tissue repair, comprising administering to a patient in need of such treatment, a pharmaceutical composition comprising a therapeutically effective amount of at least one isolated protein of the TGF-β family, wherein said protein comprises the amino acid sequence shown in SEQ ID NO. 22, and wherein said protein is selected form the group consisting of: 
 a) a protein comprising the amino acid sequence shown in SEQ ID NO:22 wherein said protein has essentially the same cartilage or bone inducing activities as a mature protein encoded by the nucleotide sequence of SEQ ID NO:1, and    b) a protein consisting of a fragment of the amino acid sequence of SEQ ID NO:3 wherein said fragment comprises the amino acid sequence shown in SEQ ID NO:22.    
     
     
         2 . The method according to  claim 1 , wherein said protein of the TGF-β family induces tissue growth and/or differentiation.  
     
     
         3 . The method according to  claim 1 , wherein said patient has bone, cartilage and/or tooth defects.  
     
     
         4 . The method according to  claim 1 , wherein said pharmaceutical composition is administered prophylactically.  
     
     
         5 . The method according to  claim 1 , wherein said patient is in need of wound healing and tissue repair.  
     
     
         6 . The method according to  claim 1 , wherein said protein of the TGF-β family suppresses an immune response.  
     
     
         7 . The method according to  claim 1 , wherein said patient is a human.  
     
     
         8 . The method according to  claim 1 , wherein said patient is a domestic animal.  
     
     
         9 . The method according to  claim 1 , wherein the pharmaceutical composition is administered as a dental implant.  
     
     
         10 . The method according to  claim 1 , wherein said at least one isolated protein of the TGF-β family is a protein comprising the amino acid sequence of SEQ ID NO:3.  
     
     
         11 . The method according to  claim 1 , wherein the isolated protein of the TGF-β family is used in combination with a pharmaceutically acceptable carrier.  
     
     
         12 . The method according to  claim 1 , wherein said pharmaceutical composition further comprises a growth/differentiation factor selected from the group consisting of MP121, epidermal growth factor and platelet derived growth factor.  
     
     
         13 . A method for the treatment of bone, tooth, connective tissue, skin, mucous membrane and endothelial, epithelial, neuronal or renal defects, for wound healing or tissue repair, as a morphogenetic factor for inducing liver tissue growth, induction of the proliferation of precursor cells or bone marrow cells, for maintaining a differentiated state and for the treatment of impaired fertility or for contraception, comprising administering a pharmaceutical composition to a patient in need of such treatment, wherein the pharmaceutical composition comprises a therapeutically effective amount of at least one isolated protein of the TGF-β family comprising the amino acid sequence shown in SEQ ID NO: 22, wherein said protein is selected form the group consisting of: 
 a) a protein comprising the amino acid sequence shown in SEQ ID NO:22 wherein said protein has essentially the same cartilage or bone inducing activities as a mature protein encoded by the nucleotide sequence of SEQ ID NO:1, and    b) a protein consisting of a fragment of the amino acid sequence of SEQ ID NO:3 wherein said fragment comprises the amino acid sequence shown in SEQ ID NO:22.    
     
     
         14 . A method for the treatment of tooth defects and/or for wound healing and tissue repair, comprising administering to a patient in need of such treatment, a pharmaceutical composition comprising a therapeutically effective amount of an isolated protein of the TGF-β family in combination with a pharmaceutically acceptable carrier, wherein said protein is encoded by a DNA comprising a nucleotide sequence selected from the following group: 
 (a) the nucleotide sequence as shown in SEQ ID NO:1,    (b) a nucleotide sequence which is degenerate as a result of the genetic code to the nucleotide sequence of (a), and    (c) fragments of (a) or (b) which encode a protein which has essentially the same cartilage or bone inducing activities as a mature protein encoded by the nucleotide sequence of SEQ ID NO:1,    
     
     
         15 . The method according to  claim 14 , wherein said protein of the TGF-β family comprises the amino acid sequence of SEQ ID NO: 3.  
     
     
         16 . The method according to  claim 14 , wherein the DNA is a mammalian DNA.  
     
     
         17 . The method according to  claim 14 , wherein the DNA comprises the nucleotide sequence shown in SEQ ID NO. 1.