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US5948428: Compositions and therapeutic methods using morphogenic proteins and stimulatory factors

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Filing Information

Inventor(s) John C. Lee · Lee-Chuan C. Yeh ·
Assignee(s) Stryker Corporation ·
Attorney/Agent(s) Fish & Neave ·
Primary Examiner Carlos Azpuru ·
Application Number US8761468
Filing date 12/06/1996
Issue date 09/07/1999
Predicted expiration date 12/12/2015
U.S. Classifications 424/426  · 523/114  ·
International Classifications A61F 228  ·
Kind CodeA
International Classifications 424426 ·
Related U.S. Application DataThis application is a continuation-in-part of U.S. application Ser. No. 08/570,752, filed on Dec. 12, 1995.
78 Claims, No Drawings


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.

Independent Claims | See all claims (78)

  1. 1. A pharmaceutical composition for inducing tissue formation in a mammal, comprising:a) a morphogenic protein capable of inducing tissue formation when accessible to a progenitor cell in the mammal;b) a morphogenic protein stimulatory factor (MPSF) capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell; andc) a pharmaceutically acceptable carrier;wherein the MPSF is selected from the group consisting of hormones, cytokines, peptides and growth factors; and provided thatwhen 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-.beta., 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-.beta.; 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.
  2. 16. 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) disposed in the carrier, the MPSF capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell;wherein the MPSF is selected from the group consisting of hormones, cytokines, peptides and growth factors; and provided thatwhen 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-.beta., the MPSF may not be FGF, IGF-II, PDGF, estrogen or 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-.beta.; 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.
  3. 30. A method for improving the tissue inductive activity of a morphogenic protein on a mammalian progenitor cell comprising the step of coadministering to the cell a morphogenic protein stimulatory factor which comprises an agent that increases IGF-1 bioactivity.
  4. 55. An implantable prosthetic device for repairing orthopedic defects, injuries or anomalies in a mammal, comprising:a) a prosthetic implant having a surface region implantable adjacent to a target tissue comprising a progenitor cell in the mammal; andb) a composition comprising an osteogenic protein and a morphogenic protein stimulatory factor (MPSF) disposed on the surface region in an amount sufficient to promote enhanced tissue growth into the surface;wherein the MPSF is selected from the group consisting of hormones, cytokines, peptides and growth factors; and provided thatwhen 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-.beta., 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-.beta.; 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.

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