Novo Nordisk A/s

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Kjeld Norris

Fanny Norris

Ole Hvilsted Olsen

Lars Christian Petersen

Donald C Foster

Cindy A Sprecher

Lars Thim

Per Franklin Nielsen

Finn C Wiberg

Mogens Christensen

Else Marie Nicolaisen

Richard Woodbury

Human spasmolytic polypeptide in glycosylated form

A variant of the C-terminal Kunitz-type protease inhibitor domain of the .alpha.3 chain of human type VI collagen, the variant comprising the following amino acid sequence X.sup.1 X.sup.16 Asp Ile Cys Lys Leu Pro Lys Asp X.sup.2 Gly X.sup.3 Cys X.sup.4 X.sup.5 X.sup.6 X.sup.7 X.sup.8 X.sup.9 Trp Tyr Tyr Asp Pro Asn Thr Lys Ser Cys Ala Arg Phe X.sup.10 Tyr Gly Gly Cys X.sup.11 X.sup.12 X.sup.13 Glu Asn Lys Phe X.sup.14 Ser Gln Lys Glu Cys Glu Lys Val Cys Ala Pro X.sup.15 (SEQ ID NO. 1) wherein X.sup.1, X.sup.15, and X.sup.16 represents a naturally occurring amino acid residues except Cys and X.sup.2 -X.sup.14 each independently respresents a naturally occurring amino acid residue, with the proviso that at least one of the amino acid residues X.sup.1 -X.sup.16 is different from the corresponding amino acid residue of the native sequence. Alternatively, the N-terminal Asp may be preceded by H or 3-5 amino acid residues and the C-terminal Pro may be followed by OH or 3-5 amino acid residues.

Human Kunitz-type protease inhibitor variants

The present invention relates to a human Kunitz-type protease inhibitor comprising the following amino acid sequence

Human kunitz-type protease inhibitor and variants thereof

This application relates to modified blood coagulation factors, DNA sequences coding for such modified factors and a process for their production.

Modified factor VII/VIIa

Variant of human Kunitz-type protease inhibitor domain II of tissue factor pathway inhibitor (TFPI), the variant comprising the following amino acid sequence ##STR1## wherein Xaa at position 1 is H or a naturally occurring amino acid residue except Cys, each Xaa at positions 2-5 is independently a naturally occurring amino acid residue except Cys or is absent, each Xaa at positions 14, 16, 18, 19, 20, 21, 22, 23, 37, 42, 43, 44, and 49 independently a naturally occurring amino acid except Cys, each Xaa at positions 61, 62, 63, and 64 is independently a naturally occurring amino acid except Cys or is absent, and Xaa at position 65 is OH or a naturally occurring amino acid except Cys, with the proviso that at least one of the amino acid residues designated Xaa is different from the amino acid residue of the native sequence.

Human Kunitz-type protease inhibitor variant

A polypeptide for production in yeast comprises a fusion of a signal peptide, a leader peptide and a heterologous protein or polypeptide. The polypeptide is modified in its amino acid sequence adjacent to a yeast processing site positioned between the C-terminal end of the leader peptide and the N-terminal end of the heterologous protein so as to provide a presentation of the processing site which makes it accessible to proteolytic cleavage. Such a presentation is provided by adding one or more amino acids (at least one of which is negatively charged) to either the C-terminal end of the leader or the N-terminal end of the protein, or both. The heterologous protein may, for instance, be aprotinin or insulin precursor or an analogue thereof.

Yeast processing system

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Lyngby, Denmark

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