Eli Lilly and Company

S Richard Jaskunas

Nils U Bang

Robert J Beckmann

Robert F Santerre

Mei-Huei T Lai

George L Long

Jo Ann Hoskins

Paul R Rosteck, Jr

Pamela Kay Rockey

Sheila P Little

Franklin H Norris

Brian W Grinnell

Genshi Zhao

Hartmut Ehrlich

Shelia P Little

The invention provides isolated nucleic acid compounds encoding a novel high molecular weight PBP of Also provided are vectors and transformed heterologous host cells for expressing the PBP and a method for identifying compounds that bind and/or inhibit the enzymatic activity of the PBP.

Penicillin binding protein from Streptococcus pneumoniae

The invention provides isolated nucleic acid compounds encoding a novel high molecular weight PBP of Streptococcus pneumoniae. Also provided are vectors and transformed heterologous host cells for expressing the PBP and a method for identifying compounds that bind and/or inhibit the enzymatic activity of the PBP.

DNA encoding a novel penicillin binding protein from streptococcus

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 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.

Vectors and compounds for direct expression of activated human protein C

The present invention provides a transcriptional and translational activating sequence derived from the lambda pL transcriptional activating sequence and the E. coli lpp translational activating sequence. The activating sequence has been cloned into recombinant DNA expression vectors into which DNA sequences encoding funtional polypeptides can be readily inserted and expressed. The activating sequence of the present invention has been shown to drive high-level expression of a bovine growth hormone derivative and a human growth hormone derivative in E. coli. Preferred expression vectors of the present invention also comprise the cI857 temperature-sensitive lambda pL repressor gene, a rop.sup.- derivative of the plasmid pBR322 replicon, and a tetracycline resistance-conferring gene.

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Indianapolis, IN, United States of America

S Richard Jaskunas