Bone morphogenetic protein compositions

Abstract

The present invention relates to compositions of bone morphogenetic proteins, particularly solid and liquid formulations of such proteins comprising one or more stabilizing excipients. The invention further provides methods of producing the compositions, kits comprising the compositions and methods of using the compositions in the treatment of diseases of skeletal and non-skeletal tissues.

1 - 10 . (canceled) 
     
     
         11 . A method of treating a skeletal tissue disorder, injury or disease, the method comprising the step of: administering to a subject in need thereof a preparation of bone morphogenetic protein comprising: an aqueous carrier; bone morphogenetic protein solubilized in said carrier at a concentration of at least about 10 mg/ml; and trehalose, wherein said protein preparation is in a dose effective to treat said skeletal tissue disorder, injury or disease. 
     
     
         12 . The method of  claim 11 , wherein the skeletal tissue is mineralized or non-mineralized skeletal tissue. 
     
     
         13 . The method of  claim 12 , wherein the protein preparation is in an amount effective to treat a skeletal tissue disorder, injury or disease selected from the group consisting of metabolic bone disease, osteoarthritis, osteochondral disease, rheumatoid arthritis, osteoporosis, bone fractures, Paget's disease, periodontitis, and dentinogenesis. 
     
     
         14 . The method of  claim 12 , wherein the protein preparation is in an amount effective to treat a non-mineralized skeletal tissue disorder, injury or disease selected from the group consisting of osteoarthritis, osteochondral disease or defect, chondral disease or defect, rheumatoid arthritis, trauma-induced and inflammation-induced cartilage degeneration, age-related cartilage degeneration, articular cartilage injuries and diseases, full thickness cartilage defects, superficial cartilage defects, sequelae of systemic lupus erythematosis, sequelae of scleroderma, periodontal tissue regeneration, hierniation and rupture of intervertebral discs, degenerative diseases of the intervertebral disc, osteocondrosis, and injuries and diseases of ligament, tendon, synovial capsule, synovial membrane and meniscal tissues. 
     
     
         15 . The method of  claim 11 , wherein the protein preparation is in an amount effective to ameliorate tissue injury selected from the group consisting of: trauma-induced and inflammation-induced cartilage degeneration, articular cartilage injuries, full thickness cartilage defects, superficial cartilage defects, hierniation and rupture of intervertebral discs, degeneration of intervertebral discs due to an injury(s), and injuries of ligament, tendon, synovial capsule, synovial membrane and meniscal tissues. 
     
     
         16 . The method of  claim 11 , wherein the disease is degenerative disc disease. 
     
     
         17 . The method of  claim 16 , wherein the effective dose is administered to the intradiscal space, the nucleus pulposus or the annulus fibrosus. 
     
     
         18 . The method of  claim 11 , wherein the method further comprises the step of admixing said protein preparation with a suitable matrix material prior to administration. 
     
     
         19 . The method of  claim 11 , wherein the protein is selected from the group consisting of: BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, GDF-5, GDF-6, GDF-7, and sequence variants of any one of the foregoing. 
     
     
         20 . The method of  claim 19 , wherein the protein is BMP-7. 
     
     
         21 - 25 . (canceled)