Prochon Biotech Ltd.

Hepacore Ltd

Other

Yeda Research and Develpment & Co. Ltd

Fibron Limited

American Cyanamid Company

Bio-technology General (israel) Ltd.

Bio-technology General Corporation

Avner Yayon

Oren Bogin

Eran Rom

Malkit Azachi

Boaz Amit

Avraham Wortzel

Micha Gladnikoff

Sara Blumenstein

Irina Chumakov

Elisabeth Thomassen-Wolf

Eric Borges

Roy Sirkis

Peter Bohlen

Zvi Nevo

Magdalena G Eisinger

Zeev Gross

Andrew P Seddon

Yigal Burstein

Orit Segev

Dalit Strauss-Ayali

Dina Lewinson

Nimrod Rozen

Hilla Barkay

Rivka Adar

Myriam Golembo

Moshe Peretz

Rachel Glicklis

David Aviezer

Luyuan Li

Hilla Barkay-Olami

The present invention relates to the design, manufacture and use of fibroblast growth factor (FGF) polypeptides having improved receptor specificity. In particular, the invention relates to isolated FGF2 polypeptides comprising a truncated N-terminus and optionally N-terminal amino acid substitutions. The present invention provides polypeptides, nucleic acids encoding the polypeptides, compositions comprising same and methods for use thereof.

FGF-2 variants having N-terminal deletions and increased receptor selectivity and methods of use thereof

Conjugates of hydrophilic carboxy polysaccharides with protein members of the fibroblast growth factor (FGF) family and variants thereof. The conjugates provide a modified bioactivity and stability of FGFs for various therapeutic applications.

Conjugates of carboxy polysaccharides with fibroblast growth factors and variants thereof

A method of treating an individual (i) having abnormal bone; or (ii) afflicted with a disease or disorder related to normal or abnormal FGF receptors or a skeletal disorder; or (iii) having dysplasic bone. The method includes administering to the individual a pharmaceutical composition comprising a therapeutically effective amount of a fibroblast growth factor 9 (FGF-9) variant comprising at least one amino acid substitution in the beta 8-beta 9 loop, wherein said FGF-9 variant incorporates one of the amino acid sequences set forth in SEQ ID NO: 11, 13, 14, 15, 16 or 17.

FGF-2 variants and methods of use thereof

The present invention relates to fibroblast growth factor 18 (FGF-18) variants having various truncations beyond the signal peptide domain of the N-terminus, which activate FGFR3 with increased specificity. The invention further relates to polynucleotides encoding the variants, pharmaceutical compositions comprising same and methods for use thereof in treating cartilage and skeletal disorders.

FGF-18 truncated variants having increased receptor specificity and uses thereof

The present invention relates to the design, manufacture and use of fibroblast growth factor (FGF) polypeptides having improved receptor specificity. In particular, the invention relates to isolated FGF2 and FGF4 polypeptides that include a truncated N-terminus and optionally N-terminal amino acid substitutions. The present invention provides polypeptides, nucleic acids encoding the polypeptides, compositions of the same and methods for use thereof.

FGF-2 variants having N-terminal deletions and increased receptor selectivity and uses thereof

Disclosed are chemically modified hyaluronic acid (HA) derivatives containing hydrazido groups directly linked to the glucuronic acid residues of HA. Said hydrazido groups are used to obtain crosslinked and labeled HA derivatives. The invention further relates to methods of preparation of said HA derivatives.

Hydrazido derivatives of hyaluronic acid

A method of treating an individual (i) having abnormal bone; or (ii) afflicted with a disease or disorder related to normal or abnormal FGF receptors or a skeletal disorder; or (iii) having dysplasic bone. The method includes administering to the individual a pharmaceutical composition comprising a therapeutically effective amount of a fibroblast growth factor 9 (FGF-9) variant comprising at least one amino acid substitution in the beta 8-beta 9 loop, wherein the FGF-9 variant incorporates one of the amino acid sequences set forth in SEQ ID NO: 11, 13, 14, 15, 16 or 17.

FGF-9 variants and methods of use thereof

Molecules comprising the antigen-binding portion of antibodies that block constitutive and/or ligand-dependent activation of a receptor protein tyrosine kinase, such as fibroblast growth factor receptor 3 (FGFR3), are found through screening methods, where a soluble dimeric form of a receptor protein tyrosine kinase is used as target for screening a library of antibody fragments displayed on the surface of bacteriophage. The molecules of the present invention which block constitutive activation can be administered to treat or inhibit skeletal dysplasia, craniosynostosis disorders, cell proliferative diseases or disorders, or tumor progression associated with the constitutive activation of a receptor protein tyrosine kinase.

Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof

Methods for treating diseased or injured tissue by implanting into the tissue at a site of the disease or injury a porous freeze-dried fibrin matrix formed from plasma proteins. The proteins include fibrinogen cleaved by the action of thrombin at varying concentrations sufficient to cleave the fibrinogen and Factor XIII. The matrix has less than 10% residual moisture and is devoid of exogenous anti-fibrinolytic agents, plasminogen and of organic chelating agents. Alternatively, the plasma proteins comprise partially purified plasma proteins that are devoid of plasminogen.

Freeze-dried fibrin matrices and methods for preparation thereof

The present invention provides fibroblast growth factor variants demonstrating enhanced receptor subtype specificity and/or affinity. Preferred embodiments include both variants having enhanced activity that act as improved agonists and variants having reduced activity that act as antagonists. Methods of utilizing preferred FGF variants in preparation of medicaments for the treatment of skeletal disorders including skeletal dysplasia, osteoporosis and enhancing bone fracture healing and cartilage healing processes are provided.

FGF-9 variants and methods for use thereof

The present invention provides water-soluble reactive esters of carboxy polysaccharides and derivatives thereof. The reactive carboxy polysaccharide derivatives are useful per se in aqueous solutions or specifically for the formation of water-soluble covalent fibrinogen conjugates. A preferred conjugate is a hyaluronic acid-fibrinogen conjugate and fibrin adhesive, clot or matrix derived from it. Methods of preparation and methods of use in tissue repair and regeneration are also disclosed.

Water soluble reactive derivatives of carboxy polysaccharides and fibrinogen conjugates thereof

The present invention relates in general to orthopedics and to a method for promoting repair of large bone defects, in particular non-union or delayed union fractures. Specifically the invention concerns the use of endothelial progenitor cell preparations for bone repair.

Methods for bone regeneration using endothelial progenitor cell preparations

Methods for producing porous freeze-dried fibrin matrices substantially devoid of external anti-fibrinolytic agents. Resilient matrices, also known as sponges, that are particularly beneficial for supporting three dimensional cell growth are obtained from plasma proteins substantially devoid of plasminogen or from partially purified plasma proteins, thus obviating the need for exogenous anti-fibrinolytic agents. Furthermore, incorporation of glycosaminoglycans and bioactive agents during the formation of the matrix results in a sponge having advantageous biological, mechanical and physical properties. The compositions made by the method of the present invention are useful clinically or as cell-bearing implants.

Growing community of inventors

Moshav Sitria, Israel

Avner Yayon