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.

What is claimed is:  
     
         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 . The method of  claim 1 , wherein the morphogenic protein comprises a pair of subunits disulfide-bonded to produce a dimeric species, wherein at least one of the subunits comprises a polypeptide belonging to the BMP protein family.  
     
     
         3 . The method of  claim 1 , wherein the morphogenic protein is an osteogenic protein.  
     
     
         4 . The method of  claim 3 , wherein the osteogenic protein is capable of inducing the progenitor cell to form endochondral or intramembranous bone.  
     
     
         5 . The method of  claim 3 , wherein the osteogenic protein is capable of inducing the progenitor cell to form cartilage.  
     
     
         6 . The method of  claim 1 , wherein the morphogenic protein is capable of inducing the progenitor cell to form tissue tendon/ligament-like or neural-like tissue.  
     
     
         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 . The method of  claim 7 , wherein the morphogenic protein comprises a polypeptide selected from the group consisting of OP-1, BMP-2, BMP-4 and BMP-6.  
     
     
         9 . The method of  claim 8 , wherein the morphogenic protein is OP-1.  
     
     
         10 . The method of  claim 2 , wherein the dimer is a homo- or heterodimer comprising a BMP-2 or BMP-7 (OP-1) subunit.  
     
     
         11 . The method of  claim 1 , wherein the hormone is interleukin 6 (IL-6).  
     
     
         12 . The method of  claim 7 , wherein the hormone is IL-6.  
     
     
         13 . The method of  claim 9 , wherein the hormone is IL-6.  
     
     
         14 . The method of  claim 1 , wherein the morphogenic protein, the hormone, and the hormone receptor are administered simultaneously to the target locus.  
     
     
         15 . The method of  claim 1 , wherein the morphogenic protein, the hormone, and the hormone receptor are administered separately to the target locus.  
     
     
         16 . The method of  claim 1 , wherein the hormone and the hormone receptor are administered simultaneously to the target locus.  
     
     
         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 . The method of  claim 1 , wherein the target locus is a neural tissue defect.  
     
     
         22 . The method of  claim 1 , wherein the morphogenic protein is administered in a matrix-comprising carrier.  
     
     
         23 . The method of  claim 22 , wherein the carrier comprises allogenic bone.  
     
     
         24 . The method of  claim 1 , wherein the morphogenic protein is administered via a nucleic acid, the nucleic acid comprising a sequence encoding the morphogenic protein and capable of expressing the morphogenic protein in the progenitor cell.  
     
     
         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 . The pharmaceutical composition of  claim 25 , further comprising an implantable, biocompatible carrier.  
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein the carrier comprises demineralized, protein-extracted, particulate, allogenic bone.  
     
     
         28 . The pharmaceutical composition of  claim 26 , wherein the carrier comprises mineral-free, delipidated Type I insoluble bone collagen particles, substantially depleted in noncollagenous protein.  
     
     
         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 . A kit for inducing tissue formation in a mammal, comprising a first receptacle containing a morphogenic protein, a second receptacle containing a hormone, and a third receptacle containing 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.  
     
     
         33 . The kit of  claim 32 , wherein the second and the third receptacles are the same.