Compositions and therapeutic methods using morphogenic proteins, hormones and hormone receptors

Abstract

This invention features devices and methods for inducing tissue formation in a mammal, involving the use of a morphogenic protein, a hormone and a soluble receptor of the hormone. The hormone and receptor thereof are used to enhance the tissue inductive activity of the morphogenic protein.

1 . A method for improving the tissue inductive capability of a morphogenic protein at a target locus in a mammal, the method comprising administering to the target locus the morphogenic protein and a first effective amount of a hormone and a second effective amount of a soluble receptor of the hormone, wherein the morphogenic protein is capable of inducing tissue formation when accessible to a progenitor cell in the mammal, and the hormone and the receptor in combination enhance that capability.  
     
     
         2 - 6 . (canceled)  
     
     
         7 . The method of  claim 1 , wherein the morphogenic protein comprises an amino acid sequence sufficiently duplicative of the amino acid sequence of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, COP-5, or COP-7.  
     
     
         8 . (canceled)  
     
     
         9 . The method of  claim 1 , wherein the morphogenic protein is OP-1.  
     
     
         10 . (canceled)  
     
     
         11 . The method of  claim 1 , wherein the hormone is interleukin 6 (IL-6).  
     
     
         12 - 16 . (canceled)  
     
     
         17 . The method of  claim 1 , wherein the target locus is a jaw bone defect.  
     
     
         18 . The method of  claim 1 , wherein the target locus is a bone defect selected from the group consisting of a fracture, a non-union fracture, a critical size defect, a non-critical size defect, an osteochondral defect, a fusion and a bony void.  
     
     
         19 . The method of  claim 1 , wherein the target locus has a tissue degenerative condition.  
     
     
         20 . The method of  claim 1 , wherein the target locus is a cartilage or soft tissue defect.  
     
     
         21 - 24 . (canceled)  
     
     
         25 . A pharmaceutical composition for inducing tissue formation in a mammal, comprising a morphogenic protein, a hormone and a soluble receptor of the hormone, wherein the morphogenic protein is capable of inducing tissue formation when accessible to a progenitor cell in the mammal, and the hormone and the receptor in combination enhance that capability.  
     
     
         26 - 28 . (canceled)  
     
     
         29 . The pharmaceutical composition of  claim 25 , wherein the morphogenic protein comprises an amino acid sequence sufficiently duplicative of the amino acid sequence of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, COP-5, or COP-7.  
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein the morphogenic protein is human OP-1.  
     
     
         31 . The pharmaceutical composition of  claim 25 , wherein the hormone is IL-6.  
     
     
         32 - 33 . (canceled)  
     
     
         34 . A method for improving the tissue inductive activity of a morphogenic protein at a target locus in a mammal, the method comprising 
 administering to the target locus a nucleic acid encoding the morphogenic protein, a nucleic acid encoding a hormone and a nucleic acid encoding a soluble receptor of the hormone, wherein the encoded morphogenic protein has tissue inductive activity when accessible to a progenitor cell in the mammal, and the encoded hormone and the encoded receptor in combination synergistically enhance the tissue inductive activity of the morphogenic protein.    
     
     
         35 . The method of  claim 34 , wherein the morphogenic protein comprises an amino acid sequence at least 70% homologous to the amino acid sequence of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, COP-5, or COP-7.  
     
     
         36 . The method of  claim 35 , wherein the morphogenic protein is BMP-7 (OP-1).  
     
     
         37 . The method of  claim 34 , wherein the hormone is interleukin 6 (IL-6) and the receptor is a soluble IL-6 receptor.  
     
     
         38 . The method of  claim 34 , wherein the target locus is a jaw bone defect.  
     
     
         39 . The method of  claim 34 , wherein the target locus is a bone defect selected from the group consisting of a fracture, a non-union fracture, a critical size defect, a non-critical size defect, an osteochondral defect, a fusion and a bony void.  
     
     
         40 . The method of  claim 34 , wherein the target locus has a tissue degenerative condition.  
     
     
         41 . The method of  claim 34 , wherein the target locus is a cartilage or soft tissue defect.