Gilead Sciences, Inc.

Lawrence L Leung

Glenn Albrecht

Craig S Gibbs

John J Toole

Linda C Griffin

John A Latham

Manuel Tsiang

Eric Vermaas

Novel polypeptides (NPs) are provided which are capable of protein C activation without significant fibrinogen clotting activity, and vice versa. NPs having enhanced protein C activating properties in relation to fibrinogen clotting are useful in particular as anticoagulants and in screening for substances that agonize or antagonize this property and in diagnostic procedures to determine the status of patients' activated protein C-mediated anticoagulant pathway. Procoagulant NPs are useful to promote clotting in the course of therapy of solid tumors, as an impregnate for bandages, or in diagnostic assays. The NPs are produced in recombinant cell culture or by in vitro methods.

Polypeptides and coagulation therapy

A method for identifying oligomer sequences, optionally comprising modified base, which specifically bind target molecules such as serum proteins, kinins, eicosanoids and extracellular proteins is described. The method is used to generate aptamers that bind to serum Factor X, PDGF, FGF, ICAM, VCAM, E-selectin, thrombin, bradykinin, PGF2 and cell surface molecules. The technique involves complexation of the target molecule with a mixture of oligonucleotides containing random sequences and sequences which serve as primer for PCR under conditions wherein a complex is formed with the specifically binding sequences, but not with the other members of the oligonucleotide mixture. The complex is then separated from uncomplexed oligonucleotides and the complexed members of the oligonucleotide mixture are recovered from the separated complex using the polymerase chain reaction. The recovered oligonucleotides may be sequenced, and successive rounds of selection using complexation, separation, amplification and recovery can be employed. The oligonucleotides can be used for therapeutic and diagnostic purposes and for generating secondary aptamers.

Aptamers specific for biomolecules and methods of making

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Hillsborough, CA, United States of America

Lawrence L Leung