Aventis Pharmaceuticals Inc.

Rhone-poulenc Rorer Pharmaceuticals Inc.

University of Pennsylvania

Dilip V Amin

Michael C Jaye

Victoria J South

Kevin J Lynch

John A Krawiec

Kim-Anh Thi Doan

Anthony C Scotese

Kent W Neuenschwander

Robert L Morris

Henry W Pauls

Yong-Mi Choi

Daniel J Rader

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

This invention relates to a class of novel phosphonate derivatives of lipophilic amines which exhibit squalene synthase inhibition properties. More specifically the compounds are bis aryl cycloalkylamino and azacycloalkyl phosphonates. Compounds of this invention reduce levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.

Phosphonate derivatives of lipophilic amines

This invention relates to polycyclic compounds containing two mono- and/or bicyclic rings and a basic tertiary amino group capable of forming an ammonium ion at biological pH and which reduces levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.

Multicyclic tertiary amine polyaromatic squalene syntase inhibitors

This invention relates to polycyclic compounds containing two mono- and/or bicyclic rings and a basic tertiary amino group capable of forming an ammonium ion at biological pH and which reduces levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention. The compounds of this invention are described by the formula ##STR1## where Ar I is phenylene or naphthylene, Ar II is phenyl or naphthyl and A is 1-azabicyclo[2.2.2]octan-3-yl.

Growing community of inventors

Lansdale, PA, United States of America

Dilip V Amin