Creative Biomolecules, Inc.

Curis, Inc.

Stryker Corporation

The Brigham and Women's Hospital, Inc.

University of Connecticut

Micromet Ag

The General Hospital Corporation

Marc F Charette

David C Rueger

Hermann Oppermann

Charles M Cohen

Thangavel Kuberasampath

Engin Ozkaynak

John E Smart

Roberto Crea

Roy H Pang

James S Huston

Roy H L Pang

Peter C Keck

Richard J Ridge

Ted Ebendal

Sandor Szabo

Seth P Finklestein

Robert B Rutherford

Zita A Babickas

OP/BMP morphogen may be combined with GDNF/NGF neurotrophic factors to promote the survival or growth, or inhibit the death or degeneration, of mammalian cells, particularly neural cells, which express OP/BMP-activated serine/threonine kinase receptors and GDNF/NGF-activated tyrosine kinase receptors. Also disclosed are methods for the treatment of such cells, including treatments for mammals afflicted with, or at imminent risk of, damage or injury to, such cells, as well as new pharmaceutical preparations for such treatments.

Synergistic effects of OP/BMP morphogens and GDNF/NGF neurotrophic factors

Disclosed is a method for the isolation and purification of polypeptides expressed in host cells by recombinant DNA techniques. A fused polypeptide is produced containing a desired polypeptide fused to additional amino acids. The additional amino acids define a leader sequence having properties exploitable in purification, a hinge region, and a cleavage site. The hinge region is cysteine-free and has a secondary structure which serves to expose the cleavage site to a selected endopeptidase. The method of the invention involves the production of a fused polypeptide which may be efficiently isolated by exploiting the properties of the leader sequence, and then efficiently cleaved at the cleavage site in an appropriate aqueous environment by virtue of the influence of the hinge on the cleavage agent/cleavage site reaction and other properties of the fused polypeptide.

Product and process for the production, isolation, and purification of recombinant polypeptide

Disclosed are methods and compositions for maintaining the integrity of the gastrointestinal tract luminal lining in a mammal, including (1) limiting epithelial cell proliferation, (2) inhibiting ulcerative lesion formation, (3) inhibiting inflammation normally associated with ulcerative diseases, and (4) stimulating the repair of ulcerative lesions and the regeneration of the luminal tissue. The methods and compositions include a therapeutically effective amount of a morphogen as defined herein.

Morphogen treatments for limiting proliferation of epithelial cells

OP/BMP morphogen is combined with GDNF/NGF neurotrophic factors in promoting the survival or growth, or inhibiting the death or degeneration, of mammalian cells, particularly neural cells, which express OP/BMP-activated serine/threonine kinase receptors and GDNF/NGF-activated tyrosine kinase receptors. Also discosed are methods for the treatment of such cells, including treatments for mammals afflicted with, or at imminent risk of, damage or injury to, such cells, as well as new pharmaceutical preparations for such treatments.

The present invention provides methods and compositions for treatment of mammals afflicted with an ischemic or traumatic injury of the central nervous system. The present invention capitalizes in part upon the discovery that administration of a morphogen to such a mammal provides significant improvement in central nervous system function, even when administered after central nervous system tissue has been damaged. The methods involve the administration of dimeric proteins defined as morphogens, inducers of these morphogens, or agonists of the corresponding morphogen receptors, or implantation of cells stimulated by exposure to the morphogens. The proteins defined as morphogens comprise a structurally and functionally distinct family within the TGF-&bgr; superfamily. Osteogenic protein-1 (OP-1) is considered to be an exemplary and preferred member of this morphogen family.

Method for enhancing functional recovery following central nervous system ischemia or trauma

Morphogen treatment of gastrointestinal ulcers

Native, analog, and mutein species of A and B chains of platelet derived growth factor are produced in prokaryotes, purified, combined, and modified in vitro to produce various active AA, AB, and BB PDGF dimers.

Production of platelet derived growth factor (PDGF) an muteins thereof

Disclosed are methods for increasing the yield of intact target proteins by cleaving fused polypeptides made by recombinant DNA techniques. The fused polypeptides are designed at the DNA level to have a preselected primary cleavage site in a pendant polypeptide fused to a protein of interest. Structural features of the fused polypeptide and cleavage reaction environment are controlled to favor cleavage by a preselected cleavage agent at the primary cleavage site over a second cleavage agent-sensitive amino acid sequence in the target protein. The cleavage reaction is terminated before completion when the ratio of intact target protein to truncated, cleaved target protein is optimized, and the remaining reaction mixture comprising uncleaved fused polypeptide is resubjected to the cleavage agent. The presence of charged organic molecules in the cleavage reaction mixture favors cleavage at the primary cleavage site. The endopeptidase used for cleavage may be immobilized on an insoluble support matrix.

Enhanced proteolytic cleavage of recombinant fusion proteins

Disclosed is a method for the regeneration of tissue, the treatment of external wounds and the treatment of periodontal disease comprising applying to the affected tissue an effective amount of a composition comprised of platelet-derived growth factor (PDGF) and an anti-inflammatory compound. The presence of the anti-inflammatory compound potentiates the activity of PDGF in stimulating cell growth, thereby enhancing tissue regeneration and/or wound healing.

Method for promoting tissue repair and regeneration using PDGF and

Disclosed is a method for treating ulcers of the gastrointestinal tract in a mammal which includes administering to the mammal a therapeutically effective amount of Platelet-Derived Growth Factor (PDGF) to the gastrointestinal tract of the mammal.

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Needham, MA, United States of America

Marc F Charette