Rhone-poulenc Rorer Pharmaceuticals Inc.

Aventis Pharmaceuticals Inc.

Osteosa Inc.

University of Pennsylvania

Rhone Poulenc Rorer

Michael C Jaye

Victoria J South

Wilson H Burgess

Dilip V Amin

Kevin J Lynch

John A Krawiec

Kim-Anh Thi Doan

William N Drohan

Thomas Maciag

Gregory R Mundy

Elzbieta Izbicka

Gregg B Crumley

Colin R Dunstan

Craig A Dionne

Joseph Schlessinger

Daniel J Rader

Yuri D Ivashchenko

George H Searfoss, Iii

George A Ricca

Christopher Cheadle

Ruth Kaplan

Ramon Lim

Stephen M French

Dawn Marchadier

Cyrille Maugeais

Lipoprotein Lipase like polypeptides, nucleic acids encoding said polypeptides, antisense sequences, and antibodies to said polypeptides are disclosed. Also disclosed are methods for the preparation of said polypeptides in a recombinant system and for the use of said polypeptides to screen for agonists and or antagonists of said polypeptides. Also disclosed are methods and compositions for the treatment of disorders of lipid metabolism.

Antibodies against LLG polypeptides of the triacylglycerol lipase family

The present invention relates to LLG polypeptides, which are polypeptides of the triacylglycerol lipase family, and fragments thereof, antibodies against such polypeptides, nucleic acids encoding such polypeptides, and antisense nucleic acids derived from such nucleic acids. The invention relates also to therapeutic compositions and methods comprising the above. In addition, the invention relates to the preparation of LLG polypeptides using recombinant technology and to the use of LLG polypeptides to screen for agonists and antagonists thereof.

LLG polypeptides of the triacylglycerol lipase family, and compositions and methods for their use in enzymatic hydrolysis, and protein and gene therapies

The present invention relates to compositions for use in raising or lowering the level of LIPG polypeptide in a patient. Embodiments of the composition include compositions comprising: an anti-sense nucleic acid; a neutralizing antibody; an intracellular binding protein; an inhibitor which inhibits the enzymatic activity of LIPG polypeptide; an inhibitor which inhibits the expression of LIPG gene; a ribozyme; an LIPG polypeptide; an enhancer which increases the enzymatic activity of LIPG polypeptide; or an enhancer which increases the expression of LIPG gene. The invention relates also to methods for using the above compositions. In addition, the invention relates to a method for diagnosing a predisposition to lower cholesterol, a method for determining whether a test compound can inhibit the enzymatic reaction between LIPG polypeptide and HDL cholesterol, and methods for determining whether a test compound can enhance the enzymatic reaction between LIPG polypeptide and LDL or VLDL cholesterol.

Compositions and methods for effecting the levels of high density lipoprotein (HDL) cholesterol and apolipoprotein AI very low density lipoprotein (VLDL) cholesterol and low density lipoprotein (LDL) cholesterol

The complete cDNA cloning of two human genes previously designated flg and bek is disclosed. These genes encode for two similar but distinct surface receptors comprised of an extracellular domain with three immunoglobulin-like regions, a single transmembrane domain, and a cytoplasmic portion containing a tyrosine kinase domain with a typical kinase insert. The expression of these two cDNAs in transfected NIH-3T3 cells led to the biosynthesis of proteins of 150 kDa and 135 kDa for flg and bek respectively. Direct binding experiments with radiolabeled acidic FGF (aFGF), basic FGF (bFGF), or kFGF inhibition of binding with native growth factors, and Scatchard analysis of the binding data indicated that bek and flg bind aFGF, bFGF, or kFGF with dissociation constants of (2-15)&times;10 M. The high affinity binding of three distinct growth factors to each of two different receptors represents a unique double redundancy without precedence among polypeptide growth factor/receptor interactions. The use of transformed host cells overexpressing flg or bek or biologically active fragments thereof for drug screening is disclosed.

Fibroblast growth factor receptors

The complete cDNA cloning of two human genes previously designated flg and bek is disclosed. These genes encode for two similar but distinct surface receptors comprised of an extracellular domain with three immunoglobulin-like regions, a single transmembrane domain, and a cytoplasmic portion containing a tyrosine kinase domain with a typical kinase insert. The expression of these two cDNAs in transfected NIH-3T3 cells led to the biosynthesis of proteins of 150 kDa and 135 kDa for flg and bek respectively. Direct binding experiments with radiolabeled acidic FGF (aFGF), basic FGF (bFGF), or kFGF inhibition of binding with native growth factors, and Scatchard analysis of the binding data indicated that bek and flg bind aFGF, bFGF, or kFGF with dissociation constants of (2-15).times.10.sup.-11 M. The high affinity binding of three distinct growth factors to each of two different receptors represents a unique double redundancy without precedence among polypeptide growth factor/receptor interactions. The use of transformed host cells overexpressing fig or bek or biologically active fragments thereof for drug screening is disclosed.

Human Bek Fibroblast growth factor receptor

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.

DNA encoding human endothelial cell growth factors and plasmids

The present invention is directed to compositions comprising endothelial cell growth factor, an acceptable carrier and, optionally, an extracellular matrix protein, a glycosaminoglycan or serum albumin. The compositions are useful for wound repair.

Compositions of human endothelial cell growth factor

The present invention provides therapeutic compositions for the prevention and treatment of pathological conditions involving bone and dental tissue. The present invention also provides a method to promote bone repair and/or growth for the treatment of pathological conditions involving bone tissue, for example, osteoporosis, Paget's disease, osteopetrosis, and periodontal disease and fracture repair, and healing of bone defects by administering FGF-1 to an animal or human in need of such treatment.

Use of fibroblast growth factors to stimulate bone growth

The present invention provides therapeutic compositions for the prevention and treatment of pathological conditions involving bone and dental tissue. The present invention also provides a method to promote bone repair and/or growth for the treatment of pathological conditions involving bone tissue, for example, osteoporosis, Paget's disease, osteopetrosis, and periodontal disease and fracture repair, and healing of bone defects by administering FGF-1 to an animal or human in need of treatment.

Endothelial cell growth factor is achieved through the application of recombinant DNA technology to prepare cloning vehicles encoding the ECGF protein and procedures are disclosed for recovering ECGF protein essentially free of other proteins of human origin. The product is useful for, among other purposes, diagnostic applications and as potential in the treatment of damaged blood vessels or other endothelial cell-lined structures.

Recombinant human endothelial cell growth factor

This invention provides a unique SH3 binding domain core motif of the sequence RPLPXXP and cDNA clones encoding proteins which interact with the SH3 domain of c-src, as well as the amino acid sequences which mediate this binding. Another embodiment of this invention is a method of identifying SH3-binding proteins and elucidating the sequences which mediate binding. This method may be used as an assay to select compounds which bind to this site and which inhibit or enhance the binding of the SH3 domain.

Expression cloning of c-src SH3-domain binding proteins

Pure homogeneous glia maturation factor is disclosed with methods for producing it from neutral sources and by molecular cloning and genetic engineering.

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Glenside, PA, United States of America

Michael C Jaye