La Jolla Pharmaceutical Company

University of California

La Jolla Pharmaceuticals Company

Lin Yu

David S Jones

Douglas Alan Livingston

Stephen M Coutts

David Matthew Marquis

Edward Jess Victoria

Edward A Dennis

Laure J Reynolds

Robert John Termansky

Richard M Jack

Chemically-defined, non-polymeric valency platform molecules and conjugates comprising chemically-defined valency platform molecules and biological or chemical molecules including polynucleotide duplexes of at least 20 base pairs that have significant binding activity for human lupus anti-dsDNA autoantibodies.

Chemically defined non-polymeric valency platform molecules and conjugates thereof

Chemically-defined non-polymeric valency platform molecules and conjugates thereof

aPL analogs that (a) bind specifically to B cells to which an aPL epitope binds and are disclosed. Optimized analogs lack T cell epitope(s) are useful as conjugates for treating aPL antibody-mediated diseases. Conjugates comprising aPL analogs and nonimmunogenic valency platform molecules are provides as are novel nonimmunogenic valency platform molecules and linkers. Methods of preparing and identifying said analogs, methods of treatment using said analogs, methods and compositions for preparing conjugates of said analogs and diagnostic immunoassays for aPL antibodies are disclosed.

APL immunoreactive peptides, conjugates thereof and methods of treatment for APL antibody-mediated pathologies

This invention provides conjugates useful for xenotransplantation which comprise a galactose &agr;1,3 galactosyl (&agr;Gal) epitope conjugated to a valency platform molecule, preferably a chemically defined valency platform molecule which allows precise valency. The invention also provides compositions comprising these conjugates, and methods (such as methods for inducing tolerance) using these conjugates and compositions.

Conjugates comprising galactose &agr;1,3 galactosyl epitopes and methods of using same

aPL analogs that (a) bind specifically to B cells to which an aPL epitope binds and are disclosed. Optimized analogs lack T cell epitope(s) are useful as conjugates for treating aPL antibody-mediated diseases. Methods of preparing and identifying said analogs, methods of treatment using said analogs, methods and compositions for preparing conjugates of said analogs and diagnostic immunoassays for aPL antibodies are disclosed.

aPL immunoreactive peptides, conjugates thereof and methods of treatment for aPL antibody-mediated pathologies

This invention relates generally to cyclic polypeptides comprising a thioether linkage and methods for their preparation. More particularly, this invention relates to halogenated polypeptides having at least one haloalanine-like amino acid, and methods for their preparation which involve converting the hydroxyl group (i.e., --OH) of a serine-like amino acid to a halo group (i.e., --X where X is Cl, Br, or I) with the aid of a phosphorus-based halogenation reagent such as a triphenylphosphine dihalide (i.e., (C.sub.6 H.sub.5).sub.3 PX.sub.2, wherein X is Cl, Br, or I), a triphenylphosphite dihalide (i.e., (C.sub.6 H.sub.5 O).sub.3 PX.sub.2, wherein X is Cl, Br, or I), or a mixture of triphenylphosphine or triphenylphosphite with a halohydrocarbon (i.e., 'halo-conversion'). This invention also relates to cyclic polypeptides having at least one polypeptide loop comprising a thioether linkage, and methods for their preparation which employ halogenated polypeptides and which involve intramolecular alkylation of the thiol group of a cysteine-like amino acid by the halo group of a haloalanine-like amino acid under suitable basic conditions to form a thioether linkage (i.e., 'cyclization').

Cyclic polypeptides comprising a thioether linkage and methods for their

Novel substrates of phospholipases, lysophospholipases and lipases are disclosed.

Carbonothioate phospholipid analogs as substrate of phospholipases and

Chemically-defined non-polymeric valency platform molecules and

A non-radioactive, spectrophotometric, microtiter plate assay for human cystolic phospholipase A.sub.2 (cPLA.sub.2) is described. The assay utilizes a novel synthetic thiol-phospholipid analog as a substrate. In one embodiment, the substrate is a phosphatidylcholine derivative with an arachidonoylthioester in the sn-2 position and an alkenyl-ether or alkenyl-ether in the sn-1 position. The alkyl-ether and the alkenyl-ether in the sn-1 position of the substrate ensures that the assay will only measure cPLA.sub.2 activity and will not be complicated by metabolism of the lysophospholipid product by the enzyme's and lysophospholypase activity.

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San Diego, CA, United States of America

Lin Yu