Eli Lilly and Company

Nils U Bang

S Richard Jaskunas

Sheila P Little

Robert J Beckmann

Robert F Santerre

Mei-Huei T Lai

George L Long

Brian W Grinnell

Hartmut Ehrlich

Brigitte E Schoner

Barbara J Weigel

S Betty Yan

Shelia P Little

The present invention comprises novel DNA compounds which encode human protein C activity. A variety of eukaryotic and prokaryotic recombinant DNA expression vectors have been constructed that comprise the novel protein C activity-encoding DNA and drive expression of protein C activity when transformed into an appropriate host cell. The novel expression vectors can be used to produce protein C derivatives, such as non-carboxylated, non-glycosylated, or non-hydroxylated protein C, and to produce protein C precursors, such as nascent or zymogen protein C, and to produce subfragments of protein C, such as active or inactive light and heavy chain. The recombinant-produced protein C activity is useful in the treatment and prevention of a variety of vascular disorders.

Vectors and compounds for expression of human protein C

The invention discloses modified forms of the enzyme tissue plasminogen activator (t-PA) in which recombinant DNA techniques are utilized to modify the structure of the t-PA cDNA to express a modified t-PA which retains the ability to activate plasminogen yet binds less efficiently to plasmin inhibitor. The invention provides novel DNA compounds and recombinant DNA expression vectors that encode modified human t-PA wherein all or a portion of the kringle protein domains of native human t-PA are removed. Both eukaryotic and prokaryotic expression vectors containing the modified t-PA DNA have been constructed and used to transform Chinese hamster ovary cells and Escherichia coli cells.

DNA encoding novel tissue plasminogen activator derivatives having

A method for the recombinant production of zymogen forms of human protein C is described. These zymogen forms differ from native zymogen protein C in their increased sensitivity to activation by thrombin and thrombin/thrombomodulin. DNA compounds, vectors, and transformants useful in the method are also disclosed.

Vectors and compounds for expression of zymogen forms of human protein C

The present invention comprises novel DNA compounds which encode human protein C activity. A variety of eukaryotic and prokaryotic recombinant DNA expression vectors have been constructed that comprise the novel protein C activity-encoding DNA and drive expression of protein C activity when transformed into an appropriate host cell. The novel expression vectors can be used to produce protein C derivatives, such as non-carboxylated, non-glycosylated, or non-hydroxylated protein C, and to produce protein C precursors, such as nascent or zymogen protein C, and to produce sub-fragments of protein C, such as active or inactive light and heavy chain. The recombinant-produced protein C activity is useful in the treatment and prevention of a variety of vascular disorders.

Methods of using recombinant human protein C

A method for the direct recombinant production of activated protein C is described. DNA compounds, vectors, and transformants useful in the method are also disclosed. The method involves transformation and culture of a host cell with a recombinant DNA vector that encodes a protein C molecule in which the activation peptide is replaced with a cleavage sequence for a cell associated protease.

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Indianapolis, IN, United States of America

Nils U Bang