Abstract: 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.

Abstract: The present invention generally relates to a pharmaceutical composition and to an improved method of preventing, attenuating and treating multiple myeloma by administering to an individual in need thereof at least one antibody to fibroblast growth factor receptor 3 (FGFR3). In particular, the at least one FGR3 antibody induces apoptosis of myeloma cells expressing wild type FGFR3.

Abstract: The present invention relates in general to chondrocyte based explants and implants of genetically engineered chondrocytes and in particular, to the delivery of peptides, proteins and RNAi molecules to a mammalian subject using a genetically modified chondrocyte-based mass. In one embodiment the genetically modified chondrocyte-based mass is provided as a chondrocyte pellet.

Abstract: 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.

Abstract: 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.

Abstract: The present invention discloses pharmaceutical compositions for the treatment of skeletal dysplasias, comprising as an active ingredient at least one natriuretic peptide. Unexpectedly, it has been shown that the natriuretic factors may be effective for bone elongation in situations of abnormal bone growth especially for achondroplasia. The effects of the natriuretic peptide may be further enhanced by prolonging its residence time or action at the target site.

Abstract: The present invention relates to porous freeze-dried plasma protein matrices having an open channel structure and a concentration gradient of plasma proteins crosslinked by the action of thrombin, and methods of producing said matrices. The compositions of the present invention are useful clinically, per se or as cell-bearing implants.

Abstract: The present invention provides a method of preventing and treating a T cell mediated disease, including inflammatory autoimmune diseases and in particular rheumatoid arthritis, by administering to an individual in need thereof at least one FGFR 3 inhibitor including a molecule comprising the antigen-binding portion of an antibody having a specific affinity for fibroblast growth factor receptor 3 (FGFR3), a FGFR3 specific small organic molecule tyrosine kinase inhibitor, a FGFR3 specific soluble receptor, a FGFR3 peptide or peptidomimetic, a FGFR3 specific RNA inhibitor, a FGFR3 specific antagonist ligand or a DNA vaccine encoding FGFR3 or a fragment thereof, or an inhibitor of heparan sulfate binding.

Abstract: The present invention provides active fibroblast growth factor variants demonstrating enhanced receptor subtype specificity. The preferred novel variants retain binding to FGF Receptor Type 3 (FGFR3) triggering intracellular downstream mechanisms leading to activation of a biological response. Methods of utilizing preferred FGF mutants in preparation of medicaments for the treatment of malignancies and skeletal disorders including osteoporosis and enhancing fracture healing and wound healing processes are provided.

Abstract: The present invention discloses pharmaceutical compositions for the treatment of skeletal dysplasias, comprising as an active ingredient at least one natriuretic peptide. Unexpectedly, it has been shown that the natriuretic factors may be effective for bone elongation in situations of abnormal bone growth especially for achondroplasia. The effects of the natriuretic peptide may be further enhanced by prolonging its residence time or action at the target site.

Abstract: The present invention discloses the isolation and use of a specific bacterial promoter region suitable for use in constructs for the high level production of heterologous proteins. This promoter is derived from the bacterial gene encoding for alcohol dehydrogenase, in particular the alcohol dehydrogenase genes isolated from the thermophilic bacterial strain T. brockii and the mesophilic bacterial strain Clostridium beijerinckii. It is now disclosed that using either the intact promoter region or certain specific fragments consisting of at least a 88 bp DNA sequence in the upstream untranslated region of the bacterial alcohol dehydrogenase gene, operatively linked to the nucleic acid sequences encoding a heterologous protein, and insertion into a DNA plasmid or any other suitable vector system, heterologous genes can be expressed in high levels in host cells. Heterologous proteins or peptides can be expressed constitutively at high levels. The proteins are obtained in their active folded form.

Abstract: The present invention relates to porous freeze-dried fibrin matrices substantially devoid of external anti-fibrinolytic agents, and methods of producing such matrices. 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 of the present invention are useful clinically, per se or as cell-bearing implants.

Abstract: A bone-enhancing composite material comprising synthetic apatite and at least one supplementary bioactive agent selected from a biocompatible polymer and an anti-resorption agent added ab initio, methods of preparing said composite and uses thereof are provided. The physical and biological properties of the composite are controlled by the addition of specific supplementary bioactive agents as well as optional therapeutic agents. The composite may be used as a powder, a paste or an implant.

Abstract: A freeze dried biocompatible matrix comprising plasma proteins, useful as implants for tissue engineering as well as in biotechnology, and methods of producing the matrix are provided. Mechanical and physical parameters can be controlled by use of auxiliary components or additives which may be removed after the matrix is formed in order to improve the biological properties of the matrix. The matrices according to the present invention may be used clinically per se, or as a cell-bearing implant.

Abstract: The present invention relates to porous freeze-dried plasma protein matrices having an open channel structure and a concentration gradient of plasma proteins crosslinked by the action of thrombin, and methods of producing said matrices. The compositions of the present invention are useful clinically, per se or as cell-bearing implants.

Abstract: 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.

Abstract: 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.

Abstract: Modulation of the activity of a heparin-binding growth factor (HBGF) by enhancing or inhibiting high affinity binding of said HBGF to its receptor, can be achieved with an agent selected from: (i) a soluble CD44 isoform carrying at least one chain of a heparan sulfate; (ii) a recombinant chimeric fusion protein comprising the amino acid sequence of a soluble CD44 isoform fused to a tag suitable for proteoglycan purification, said fusion molecule being post-translationally glycosylated to carry at least one chain of a heparan sulfate; and (iii) a sugar molecule being a heparan sulfate derived from a CD44 isoform, or a fragment thereof. The agents (i) and (ii) when the soluble CD44 isoform is the soluble CD44 variant expressed in synovial cells of rheumatoid arthritis patients (CD44vRA), and the heparan sulfate of (iii), are novel.

Abstract: A freeze-dried biocompatible matrix that includes plasma proteins that are useful as implants for tissue engineering as well as in biotechnology. Methods of producing the matrix are also provided. Mechanical and physical parameters can be controlled by the use of auxiliary components or additives which may be removed after the matrix is formed in order to improve the biological properties of the matrix. These matrices may be used clinically per se or as a cell-bearing implant.

Abstract: The present invention discloses pharmaceutical compositions for the treatment of skeletal dysplasias, comprising as an active ingredient at least one natriuretic peptide. Unexpectedly, it has been shown that the natriuretic factors may be effective for bone elongation in situations of abnormal bone growth especially for achondroplasia. The effects of the natriuretic peptide may be further enhanced by prolonging its residence time or action at the target site.