Genentech, Inc.

University of Vermont and State Agricultural College

Grenentech, Inc.

Bruce A Keyt

Napoleone Ferrara

Francis Hung Nguyen

Leonard G Presta

Stephen P Anderson

Kevin M Brady

William F Bennett

Mark Zoller

James A Wells

Larry L Green

Nicholas F Paoni

Brian C Cunningham

Bing Li

Martin M Bednar

Cordell E Gross

Stephen Charles Emery

Neelima M Bhat

Marcia M Bieber

Nelson Nh Teng

Qing Zhou

Xiao-Dong Yang

David C Blakey

The present invention involves the preparation of vascular endothelial growth factor (VEGF) variants which provide materials that are selective in respect of binding characteristics to the kinase domain region and the FMS-like tyrosine-kinase region, respectively KDR and FLT-1. The respective KDR and FLT-1 receptors are bound by corresponding domains within the VEGF compound domains. The variants hereof define those two binding regions and modify them so as to introduce changes that interrupt the binding to the respective domain. In this fashion the final biological characteristics of the VEGF molecule are selectively modified.

Variants of vascular endothelial cell growth factor, their uses, and processes for their production

The present invention involves the preparation of vascular endothelial growth actor (VEGF) variants which provide materials that are selective in respect to binding characteristics to the kinase domain region and the FMS-like tyrosine-kinase region, respectively KDR and FLT-1. The respective KDR and FLT-1 receptors are bound by corresponding domains within the VEGF compound domains. The variants hereof define those two binding regions and modify them so as to introduce changes that interrupt the binding to the respective domain. In this fashion the final biological characteristics of the VEGF molecule are selectively modified.

Variants of vascular endothelial cell growth factor

The present invention involves the preparation of vascular endothelial growth factor (VEGF) antagonist molecules comprising variant VEGF polypeptides which are capable of binding to and occupying cell surface VEGF receptors without inducing a VEGF response, thereby antagonizing the biological activity of the native VEGF protein. Specifically, the variant VEGF polypeptides of the present invention comprise modifications of at least one cysteine residue in the native VEGF sequence, thereby inhibiting the ability of the variant polypeptide to dimerize through the formation of disulfide bonds. The present invention is further directed to methods for preparing such variant VEGF antagonists and to methods, compositions and assays utilizing such variants for producing pharmaceutically active materials having therapeutic and pharmacologic properties that differ from the native VEGF protein.

Variants of vascular endothelial cell growth factor having antagonistic properties, nucleic acids encoding the same and host cells comprising those nucleic acids

The present invention involves the preparation of vascular endothelial growth factor (VEGF) variants which provide materials that are selective in respect to binding characteristics to the kinase domain region and the FMS-like tyrosine-kinase region, respectively KDR and FLT-1. The respective KDR and FLT-1 receptors are bound by corresponding domains within the VEGF compound domains. The variants hereof define those two binding regions and modify them so as to introduce changes that interrupt the binding to the respective domain. In this fashion the final biological characteristics of the VEGF molecule are selectively modified.

Nucleic acids encoding variants of vascular endothelial cell growth

Methods and products are provided for treating thromboembolic stroke. A method involves the administration of a thienopyridine derivative in combination with a thrombolytic agent to a patient suffering from thromboembolic stroke. Preferably the thienopyridine derivative is ticlopidine and the thrombolytic agent is tPA. The method also involves the administration of a thrombolytic agent to a subject who already has circulating plasma levels of a thienopyridine derivative. The product is a pharmaceutical preparation of a thienopyridine derivative and a thrombolytic agent and a pharmaceutically acceptable carrier.

Thrombolytic agents and thienopyridine derivatives in acute stroke

The invention concerns tissue plasminogen activator (t-PA) variants which are glycosylated at any of positions 103-105, and are devoid of functional carbohydrate structure at position 117 of wild-type human t-PA amino acid sequence. The variants have extended circulatory half-life and substantially retained fibrin binding, or improved in vivo fibrinolytic potency, as compared to wild-type human t-PA.

Tissue plasminogen activator glycosylation variants with improved

A fibrinolytically active amino acid sequence variant of a plasminogen activator is prepared that has one or more glycosylation sites in regions that are not glycosylated in the native molecule. DNA sequences can be prepared that encode the variants, as well as expression vectors incorporating the DNA sequences, and host cells transformed with the expression vectors. The variants may be used in a pharmaceutical preparation to treat a vascular disease or condition in patients.

Variants of plasminogen activators and processes for their production

Variants of tissue plasminogen activator, compositions and methods of

DNA encoding variants of tissue plasminogen activators and expression

Biologically active tissue plasminogen activator (t-PA) variants with decreased clearance as compared to wild-type t-PA are prepared, including variants that have one or more amino acid alterations in at least the kringle-1 and/or kringle-2 domain(s) of the molecule. DNA sequences can be prepared that encode the variants, as well as expression vectors incorporating the DNA sequences and host cells transformed with the expression vectors. The variants may be used in pharmaceutical preparations to treat a vascular disease or condition, or to prevent fibrin deposition or adhesion formation or reformation in mammals.

Tissue plasminogen activator variants with decreased clearance

DNA molecules encoding variants of tissue plasminogen activators,

DNA molecules encoding human tissue plasminogen activator variants with

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Pacifica, CA, United States of America

Bruce A Keyt