American National Red Cross

Maine Medical Center Research Institute

Rhone-poulenc Rorer Pharmaceuticals Inc.

Other

Repair, Inc.

The United States of America As Represented by the American National Red

Thomas Maciag

William N Drohan

Wilson H Burgess

Martin James MacPhee

Gene Liau

Hernan Nunez

Ann B Zimrin

Gregory M Fahy

Michael C Jaye

Bijan S Khirabadi

Yasumitsu Okouchi

Manish S Singh

Deena J Small

Roberto Montesano

Michael S Pepper

Igor A Prudovsky

Michael Wong

Jeffrey O Hollinger

Martin J Macphee

Howard P Greisler

Willson H Burgess

David S Ettenson

This invention relates to therapeutic and diagnostic methods and compositions based on Jagged/Notch proteins and nucleic acids, and on their role in the signaling pathway relating to endothelial cell migration and/or differentiation. In addition, this invention provides a substantially purified Jagged protein, as well as a substantially purified nucleic acid or segment thereof encoding Jagged protein, or a functionally equivalent derivative, or allelic or species variant thereof. Further, this invention provides a substantially purified soluble Jagged protein and a substantially purified nucleic acid encoding same as well as a recombinant cell comprising a nucleic acid encoding a soluble Jagged protein. Soluble Jagged provides further therapeutic and diagnostic methods relating to diseases, disorders, and conditions involving Jagged/Notch signaling including, inter alia, angiogenesis, differentiation, and control of gene expression.

Therapeutic and diagnostic methods and compositions based on jagged/notch proteins and nucleic acids

This invention provides supplemented and unsupplemented tissue sealants as well as methods for their production and use thereof. Disclosed are tissue sealants supplemented with at least one antibody. The composition may be further supplemented with, for example, one or more analgesics, antimicrobial compositions, anticoagulants, antiproliferatives, anti-inflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like.

Supplemented fibrin matrix delivery systems

This invention provides supplemented and unsupplemented tissue sealants as well as methods for their production and use thereof. Disclosed are tissue sealants supplemented with at least one antimicrobial composition. The composition may be further supplemented with, for example, one or more antibodies, analgesics, anticoagulants, antiproliferatives, anti-inflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like.

Methods for treating wound tissue and forming a supplemented fibrin matrix

This invention provides a fibrin sealant bandage, wherein said fibrin sealant may be supplemented with at least one composition selected from, for example, one or more regulatory compounds, antibody, antimicrobial compositions, analgesics, anticoagulants, antiproliferatives, anti-inflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Also disclosed are methods of preparing and/or using the unsupplemented or supplemented fibrin sealant bandage.

Supplemented and unsupplemented tissue sealants, methods of their production and use

This invention provides a fibrin sealant dressing, wherein said fibrin sealant may be supplemented with at least one composition selected from, for example, one or more regulatory compounds, antibody, antimicrobial compositions, analgesics, anticoagulants, antiproliferatives, antiinflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Also disclosed are methods of preparing and/or using the unsupplemented or supplemented fibrin sealant dressing.

This invention provides methods for the localized delivery of supplemented tissue sealants, wherein the supplemented tissue sealants comprise at least one composition which is selected from one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, antiproliferatives, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Further provided are methods of using the site-specific supplemented tissue sealants, including preparation of a biomaterial.

This invention provides supplemented tissue sealants, methods for their production and use thereof. Disclosed are tissue sealants supplemented with at least one cytotoxin or cell proliferation inhibiting composition. The composition may be further supplemented with, for example, one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, cytokines, drugs, growth factors, interferons, hormones, lipids, deminearlized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like.

The invention relates to novel degradation resistant FGF-1, and methods for producing and using the same. More specifically, the invention relates to identification of a thrombin degradation resistant FGF-1, an a nucleic acid encoding the same. The thrombin degradation resistant FGF-1 can elicit responses that are otherwise typically impeded by degradation of FGF-1 by thrombin. Thrombin degradation resistant FGF-1 is an important molecule for effecting an FGF-1 response that would be otherwise inhibited by thrombin. Thus, the present invention provides a powerful therapeutic for diseases or disorders wherein an FGF-1 response can mediate a reduction in the frequency or intensity of a symptom of the disease or disorder but for degradation of FGF-1 before it can effect the response.

Compositions, methods and kits relating to thrombin degradation resistant fibroblast growth factor-1

This invention relates to therapeutic and diagnostic methods and compositions based on Jagged/Notch proteins and nucleic acids, and on the role of their signaling pathway in endothelial cell migration and/or differentiation. In addition, this invention provides a substantially purified Jagged protein, as well as a substantially purified nucleic acid molecule or segment thereof encoding Jagged protein, or a functionally equivalent derivative, or allelic or species variant thereof.

Therapeutic and diagnostic methods and compositions based on Jagged/Notch proteins and nucleic acids

This invention provides methods for the preparation of a tissue sealant-treated biomaterial, wherein the tissue sealant used in the method comprises at least one composition which is selected from one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, antiproliferatives, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Further provided are the biomaterial prepared therefrom, including vascular grafts.

Method of preparing a tissue sealant-treated biomedical material

The invention relates to the field of organ and tissue perfusion. More particularly, the present invention relates to a method for preparing organs, such as the kidney and liver, for cryopreservation through the introduction of vitrifiable concentrations of cryoprotectant into them. To prepare the organ for cryopreservation, the donor human or animal, is treated in the usual manner and may also be treated with iloprost, or other vasodilators, and/or transforming growth factor &bgr;1. Alternatively, or additionally, the organ which is to be cryopreserved can be administered iloprost, or other vasodilators, and/or transforming growth factor &bgr;1 directly into its artery. The invention also relates to preparing organs for transplantation by a method for the removal of the cryoprotectant therefrom using low (such as raffinose, sucrose, mannitol, etc.), medium (such as agents with intermediate molecular weights of around 600-2,000) and high (such as hydroxyethyl starch) molecular weight agents osmotic buffering agents. The invention is also directed to new post-transplantation treatments such as the use of transforming growth factor &bgr;1, N-acetylcysteine and aurothioglucose.

Method for preparing organs for transplantation after cryopreservation

The invention relates to the field of organ and tissue perfusion. More particularly, the present invention relates to a method for preparing organs, such as the kidney and liver, for cryopreservation through the introduction of vitrifiable concentrations of cryoprotectant into them. To prepare the organ for cryopreservation, the donor human or animal, is treated in the usual manner and may also be treated with iloprost, or other vasodilators, and/or transforming growth factor .beta.1. Alternatively, or additionally, the organ which is to be cryopreserved can be administered iloprost, or other vasodilators, and/or transforming growth factor .beta.1 directly into its artery. The invention also relates to preparing organs for transplantation by a method for the removal of the cryoprotectant therefrom using low (such as raffi nose, sucrose, mannitol, etc.), medium (such as agents with intermediate molecular weights of around 600-2,000) and high (such as hydroxyethyl starch) molecular weight agents osmotic buffering agents. The invention is also directed to new post-transplantation treatments such as the use of transforming growth factor .beta.1, N-acetylcysteine and aurothioglucose.

Method of preparing tissues and cells for vitrification

The present invention is directed to DNA encoding human endothelial cell growth factors, and to plasmids comprising said DNA. In particular, the invention relates to DNA encoding a cleavable signal peptide and an endothelial cell growth factor, wherein removal of said signal peptide yields a mature form of the growth factor.

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Freeport, ME, United States of America

Thomas Maciag