Abstract: Human spasmolytic polypeptide (HSP) which has the amino acid sequence Glu Lys Pro Ser Pro Cys Gln Cys Ser Arg Leu Ser Pro His Asn Arg Thr Asn Cys Gly Phe Pro Gly Ile Thr Ser Asp Gln Cys Phe Asp Asn Gly Cys Cys Phe Asp Ser Ser Val Thr Gly Val Pro Trp Cys Phe His Pro Leu Pro Lys Gln Glu Ser Asp Gln Cys Val Met Glu Val Ser Asp Arg Arg Asn Cys Gly Tyr Pro Gly Ile Ser Pro Glu Glu Cys Ala Ser Arg Lys Cys Cys Phe Ser Asn Phe Ile Phe Glu Val Pro Trp Cys Phe Phe Pro Asn Ser Val Glu Asp Cys His Tyr or a functionally equivalent homologue thereof, characterized by being in glycosylated form.

Abstract: Human spasmolytic polypeptide (HSP) which has the amino acid sequence Glu Lys Pro Ser Pro Cys Gln Cys Ser Arg Leu Ser Pro His Asn Arg Thr Asn Cys Gly Phe Pro Gly Ile Thr Ser Asp Gln Cys Phe Asp Asn Gly Cys Cys Phe Asp Ser Ser Val Thr Gly Val Pro Trp Cys Phe His Pro Leu Pro Lys Gln Glu Ser Asp Gln Cys Val Met Glu Val Ser Asp Arg Arg Asn Cys Gly Tyr Pro Gly Ile Ser Pro Glu Glu Cys Ala Ser Arg Lys Cys Cys Phe Ser Asn Phe Ile Phe Glu Val Pro Trp Cys Phe Phe Pro Asn Ser Val Glu Asp Cys His Tyr or a functionally equivalent homologue thereof, characterized by being in glycosylated form.

Abstract: The present invention relates to providing antibodies against human heparin-binding protein (hHBP) or against a homologue of hHBP, such as porcine heparin binding protein (pHBP) or human neutrophil elastase (hNEL), and using said antibodies for the manufacture of a medicament for treatment of Gram positive and/or Gram negative infections, sepsis, disseminated intravascular coagulation, modulation of inflammatory response, and/or prevention of cell apoptosis. Antibodies of the invention are capable of modulating at least one inflammatory response associated with hHBP, in particular, the invention relates to monoclonal antibody F19A5B1, capable of stimulating said at least one inflammatory response, and monoclonal antibody F19A5B4, capable of inhibiting said at least one inflammatory response.

Abstract: The present invention relates to providing new peptide fragments derived from the sequence of heparin-binding protein (HBP) and/or human neutrophil elastase and using said fragments for the manufacture of a medicament for the treatment of Gram positive and/or Gram negative infections. Thus, the peptides of the inventions can be used for treatment of pneumonia and/meningitis. The peptides of the invention may also be advantageously used for the treatment of any pathological condition demanding modulating of inflammatory response and/or a condition involving sepsis and/or, disseminated intravascular coagulation. Among other pathological conditions, which may be regarded for the treatment with the peptides of the invention, are conditions involving cell apoptosis.

Abstract: Human spasmolytic polypeptide (HSP) which has the amino acid sequence Glu Lys Pro Ser Pro Cys Gln Cys Ser Arg Leu Ser Pro His Asn Arg Thr Asn Cys Gly Phe Pro Gly Ile Thr Ser Asp Gln Cys Phe Asp Asn Gly Cys Cys Phe Asp Ser Ser Val Thr Gly Val Pro Trp Cys Phe His Pro Leu Pro Lys Gln Glu Ser Asp Gln Cys Val Met Glu Val Ser Asp Arg Arg Asn Cys Gly Tyr Pro Gly Ile Ser Pro Glu Glu Cys Ala Ser Arg Lys Cys Cys Phe Ser Asn Phe Ile Phe Glu Val Pro Trp Cys Phe Phe Pro Asn Ser Val Glu Asp Cys His Tyr or a functionally equivalent homologue thereof, characterized by being in glycosylated form.

Abstract: Human spasmolytic polypeptide (HSP) which has the amino acid sequence Glu Lys Pro Ser Pro Cys Gln Cys Ser Arg Leu Ser Pro His Asn Arg Thr Asn Cys Gly Phe Pro Gly Ile Thr Ser Asp Gln Cys Phe Asp Asn Gly Cys Cys Phe Asp Ser Ser Val Thr Gly Val Pro Trp Cys Phe His Pro Leu Pro Lys Gln Glu Ser Asp Gln Cys Val Met Glu Val Ser Asp Arg Arg Asn Cys Gly Tyr Pro Gly Ile Ser Pro Glu Glu Cys Ala Ser Arg Lys Cys Cys Phe Ser Asn Phe Ile Phe Glu Val Pro Trp Cys Phe Phe Pro Asn Ser Val Glu Asp Cys His Tyr or a functionally equivalent homologue thereof, characterized by being in glycosylated form.

Abstract: The present invention relates to aprotinin variants having improved enzyme-inhibitory, immunological and pharmacokinetic properties and their preparation.

Abstract: A human spasmolytic polypeptide (HSP) having the amino acid SEQ ID NO:1, characterized by being in a glycosylated form.

Abstract: The present invention relates to aprotinin variants having improved enzyme-inhibitory, immunological and pharmacokinetic properties and their preparation.

Abstract: The present invention relates to aprotinin variants having improved enzyme-inhibitory, immunological and pharmacokinetic properties and their preparation.

Abstract: A human spasmolytic polypeptide (HSP) having the amino acid of SEQ ID NO:1, characterized by being in a glycosylated form.

Abstract: 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.

Abstract: The present invention relates to methods for producing aprotinin and analogs thereof in yeast, synthetic genes encoding such products, expression vectors and transformed yeast cells. The invention further relates to aprotinin analogs, particularly analogs with increased specific inhibitory activity and/or reduced nephrotoxicity compared to native aprotinin, as well as compositions comprising such analogs.

Abstract: The present invention relates to a human Kunitz-type protease inhibitor comprising the following amino acid sequenceAsp Leu Leu Pro Asn Val Cys Ala Phe Pro Met Glu Lys Gly Pro Cys Gln Thr Tyr Met Thr Arg Trp Phe Phe Asn Phe Glu Thr Gly Glu Cys Glu Leu Phe Ala Tyr Gly Gly Cys Gly Gly Asn Ser Asn Asn Phe Leu Arg Lys Glu Lys Cys Glu Lys Phe Cys Lys Phe Thr(SEQ ID NO:1)or a variant thereof with protease inhibitor properties.

Abstract: The present invention relates to methods for producing aprotinin and analogs thereof in yeast, synthetic genes encoding such products, expression vectors and transformed yeast cells. The invention further relates to aprotinin analogs, particularly analogs with increased specific inhibitory activity and/or reduced nephrotoxicity compared to native aprotinin, as well as compositions comprising such analogs.

Abstract: Novel rapid-acting human insulin analogues are provided having less tendency to self-association into dimers, tetramers, hexamers, or polymers. The novel human insulin analogues are formed by substituting one or more of the amino acid residues of human insulin with naturally occuring amino acid residues. The amino acid residue substitutions are preferably more hydrophilic than the natural amino acid residue at the respective position in the molecule. Furthermore, the insulin analogues have the same charge or a greater negative charge at neutral pH than that of human insulin. Preferred amino acid substitutions are Asp, Glu, Ser, Thr, His, and Ile, and more preferred substitutions are Asp and Glu. The novel insulin analogues can be used for the preparation of rapid-acting insulin solutions.

Abstract: The present invention relates to methods for producing aprotinin and analogs thereof in yeast, synthetic genes encoding such products, expression vectors and transformed yeast cells. The invention further relates to aprotinin analogs, particularly analogs with increased specific inhibitory activity and/or reduced nephrotoxicity compared to native aprotinin, as well as compositions comprising such analogs.

Abstract: 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.

Abstract: 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.

Abstract: 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.