Monsanto Company

G.d. Searle & Company

Washington University

Tze-Chein Wun

George J Broze, Jr

Kuniko K Kretzmer

Leslie D Bell

Mark O Palmier

Ernest J Mayer

H Eser Tolunay

Thomas G Warren

Roger K Khouri

J Evan Sadler

Mark E Gustafson

Judy A Diaz-Collier

Basem Koudsi

Peter G Tipping

David M Brown

Jasper Evan Sadler

Kuniko Kusano Kretzmer

Mark E Gustofson

Judith A Diaz-Collier

George John Broze

There is disclosed herein a combination of lipoprotein-associated coagulation inhibition (LACI) and sulfated polysaccharides, e.g. heparin, which exerts a synergistic anticoagulant action in whole plasma.

Anticoagulant combination of LACI and sulfated polysaccharides

A method is disclosed for inhibiting intimal hyperplasia in a warm-blooded mammal which comprises administering topically at the site and time of a vascular injury induced by arterial intervention in said mammal a small but inhibitorily effective amount of tissue factor pathway inhibitor (TFPI) sufficient to inhibit said intimal hyperplasia.

Method of inhibiting intimal hyperplasia

A cDNA clone having a base sequence for human tissue factor inhibitor (TFI) has been developed and characterized and the amino acid sequence of the TFI has been determined.

Human tissue factor inhibitor

A pre-formed anticoagulant heparin/TFPI complex which consists of a weight ratio of at least 1.25 parts of heparin to one part of TFPI and its use in inhibiting blood cogulation.

Pre-formed anticoagulant heparin/TFPI complexes

There is disclosed a method of inhibiting fibrin dependent glomerulonephritis which comprises administering to a warm-blooded mammal a heparin/TFPI complex which consists of a weight ratio of at least 1.25 parts of heparin to one part of TFPI.

Method of inhibiting glomerulonephritis

DNA clone of human tissue factor inhibitor

A method for reducing the extent of tissue ischemia and reperfusion injury in a warm-blooded mammal is disclosed which comprises administering by local, regional, or systemic perfusion to the site of a bodily injury subject to interval tissue ischemia in said mammal a small but effective amount of tissue factor pathway inhibitor (TFPI) sufficient to reduce the extent of said tissue ischemia and reperfusion injury.

Method of inhibiting tissue ischemia and reperfusion injury

A method for reducing the thrombogenicity of microvascular anastomoses in a warm blooded mammal comprising administering to said mammal at the site of said microvascular anastomoses contemporaneously with microvascular reconstruction of a small but inhibitory effective amount of TFPI.

Method of inhibiting microvascular thrombosis

A modified t-PA having improved in vivo half-life is disclosed comprising in sequence a fibronectin finger-like domain F, a growth factor domain GF, a sequence of two K2 kringle regions and a serine protease region SP, wherein the first of said kringles is free of any glycosylation site and the second of said kringles has a single glycosylation site.

Modified tissue plasminogen activator with modified glycosylation site

A method is disclosed for the production of tissue factor pathway inhibitor (TFPI) which comprises expression of a non-glycosylated form of TFPI in E. coli as host and obtaining a highly active TFPI by in vitro refolding of the protein in which inclusion bodies isolated from the E. coli cells are subjected to stepwise purification comprising either series (A) or series (B) as follows: (A)

Method of producing tissue factor pathway inhibitor

A method of purifying PAI-1 from a biological fluid source, e.g. conditioned media of Hep G2 or HT 1020 cells, containing PAI-1 is disclosed, which comprises subjecting the biological fluid to a modified urokinase affinity absorbent, e.g. anhydrourokinase ligand bound to a CNBr-activated agarose gel or urokinase mutated at amino acid position 356 from Ser to Gly and bound to the gel, and then eluting PAI-1 from said affinity absorbent. A method of stabilizing and/or activating PAI-1 is also disclosed, which comprises complexing PAI-1 with vitronectin.

Method of stabilizing plasminogen activator inhibitor by treatment with

A modified t-PA having improved in vivo half-life is disclosed comprising in sequence a sequence of two K2 kringle regions and a serine protease region SP.

Modified tissue plasminogen activator K2K2SP

A method of purifying PAI-1 from a biological fluid source, e.g. conditioned media of Hep G2 or HT 1080 cells, containing PAI-1 is disclosed, which comprises subjecting the biological fluid to a modified urokinase affinity absorbent, e.g. anhydrourokinase ligand bound to a CNBr-activated agarose gel or urokinase mutated at amino acid position 356 from Ser to Gly and bound to the gel, and then eluting PAI-1 from said affinity absorbent. A method of stabilizing and/or activating PAI-1 is also disclosed, which comprises complexing PAI-1 with vitronectin.

Affinity purification of plasminogen activator inhibitor I using a

A modified tissue plasminogen activator having an improved in vivo half-life characterized in that the normal protein moiety of 527 amino acids is mutated at the site Cys73.fwdarw.Arg and at the site Lys277.fwdarw.Asp.

Growing community of inventors

St. Louis, MO, United States of America

Tze-Chein Wun