Eli Lilly and Company

Barbara J Weigel

Brigitte E Schoner

Thomas D Ingolia

Robert Alan Gadski

Lisa Selsam Beavers

Thomas F Bumol

Sheila P Little

Nils U Bang

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

The present invention comprises novel recombinant DNA compounds which encode monoclonal antibody KS1/4 and chimeric derivatives of monoclonal antibody KS1/4. Eukaryotic expression vectors have been constructed that comprise novel KS1/4-encoding DNA and drive expression of KS1/4 when transformed into an appropriate host cell. The novel expression vectors can be used to create modified and chimeric derivatives of KS1/4. The recombinant-produced KS1/4, KS1/4 derivatives and KS1/4 chimeras are useful for the diagnosis, prognosis and treatment of disease states including adenocarcinoma.

Recombinant and chimeric KS1/4 antibodies directed against a human

DNA compounds encoding the Streptomyces lipmanii isopenicillin N synthetase (IPNS) gene are useful for constructing a variety of recombinant DNA vectors. The vectors are useful in producing IPNS in a wide variety of host cells, such as Streptomyces, Penicillium, and Cephalosporium. DNA compounds encoding the transcription and translation activating sequence and transcription termination sequence of the S. lipmanii IPNS gene are also useful in the construction of expression vectors, especially Streptomyces expression vectors. The S. lipmanii IPNS gene can be isolated from plasmid pOGO239, available from the Northern Regional Research Center under accession number NRRL B-18250.

Recombinant DNA expression vectors and DNA compounds that encode

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Indianapolis, IN, United States of America

Barbara J Weigel