Compositions and therapeutic methods using morphogenic proteins and stimulatory factors
First Claim
1. A morphogenic device for implantation in a mammal, the device comprising:
- a) an implantable biocompatible carrier,b) a morphogenic protein disposed in the carrier, the morphogenic protein capable of inducing tissue formation when accessible to a progenitor cell, andc) a morphogenic protein stimulatory factor (MPSF) selected from the group consisting of hormones, cytokines, peptides and growth factors disposed in the carrier, the stimulatory factor capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell;
with the proviso that when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is activin, the MPSF may not be estrogen or calcitonin;
when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic Protein is a BMP homodimer or TGF-β
, the MPSF may not be FGF, IGF-II, PDGF, estrogen, calcitonin or vitamin D;
when the progenitor cell is an osteoblast stimulated to form bone or cartilage and the morphogenic protein is a BMP homodimer, the MPSF may not be TGF-β
; and
when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone.
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Accused Products
Abstract
The present invention provides pharmaceutical compositions comprising a morphogenic protein stimulatory factor (MPSF) for improving the tissue inductive activity of morphogenic proteins, particularly those belonging to the BMP protein family. Methods for improving the tissue inductive activity of a morphogenic protein in a mammal using those compositions are provided. This invention also provides implantable morphogenic devices comprising a morphogenic protein and a MPSF disposed within a carrier, that are capable of inducing tissue formation in allogeneic and xenogeneic implants. Methods for inducing local tissue formation from a progenitor cell in a mammal using those devices are also provided. A method for accelerating allograft repair in a mammal using morphogenic devices is provided. This invention also provides a prosthetic device comprising a prosthesis coated with a morphogenic protein and a MPSF, and a method for promoting in vivo integration of an implantable prosthetic device to enhance the bond strength between the prosthesis and the existing target tissue at the joining site. Methods of treating tissue degenerative conditions in a mammal using the pharmaceutical compositions are also provided.
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Citations
42 Claims
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1. A morphogenic device for implantation in a mammal, the device comprising:
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a) an implantable biocompatible carrier, b) a morphogenic protein disposed in the carrier, the morphogenic protein capable of inducing tissue formation when accessible to a progenitor cell, and c) a morphogenic protein stimulatory factor (MPSF) selected from the group consisting of hormones, cytokines, peptides and growth factors disposed in the carrier, the stimulatory factor capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell; with the proviso that when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is activin, the MPSF may not be estrogen or calcitonin; when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic Protein is a BMP homodimer or TGF-β
, the MPSF may not be FGF, IGF-II, PDGF, estrogen, calcitonin or vitamin D;when the progenitor cell is an osteoblast stimulated to form bone or cartilage and the morphogenic protein is a BMP homodimer, the MPSF may not be TGF-β
; andwhen the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42)
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19. An implantable prosthetic device for repairing orthopedic defects, injuries or anomalies in a mammal, comprising:
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a) a prosthetic implant having a surface region implantable adjacent to a target tissue in the mammal; and b) a composition comprising an osteogenic protein capable of inducing tissue formation when accessible to a progenitor cell and a morphogenic protein stimulatory factor (MPSF) capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell, said morphogenic Protein and MPSF disposed on the surface region in an amount sufficient to promote from a progenitor cell enhanced tissue growth between the target tissue and the device; with the proviso that when the progenitor cell is an osteoblast stimulated to form bone and the morphoaenic protein is activin, the MPSF may not be estrogen or calcitonin; when the prozenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer or TGF-β
, the MPSF may not be FGF, IGF-II, PDGF, estrogen, calcitonin or vitamin D;when the progenitor cell is an osteoblast stimulated to form bone or cartilage and the morphogenic protein is a BMP homodimer, the MPSF may not be TGF-β
; andwhen the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27)
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Specification