Abstract: A method of treating a disease or condition in which up-regulating GAGs is therapeutically beneficial is disclosed, in particular osteoarthritis and skin diseases. The method comprises locally administering to a subject a therapeutically effective amount of an agent capable of down-regulating activity or expression of a component of the renin-angiotensin system.

Abstract: The present invention relates to compositions and methods for inhibiting the activity of an enzyme, for example, Protein Kinase B, p70S6K and/or Abl using the catalytic subunit of Protein Kinase A (PKAc), or at least one PKAc fragment or variant PKAc fragment thereof. In this regard, methods for preventing or treating cancer or a neurodegenerative disease or disorder are also provided.

Abstract: The invention relates to storable medicaments produced from pharmaceutical active ingredient preparations which are virus safe. Said medicaments contain at least one intact therapeutic protein obtained from plasma or by means of genetic engineering, as an active pharmaceutical substance. Said active ingredient preparations contain active enzymes, especially proteases, which are either free or bound to the substrates thereof and act against the therapeutic protein(s) present.

Abstract: The instant invention provides a method of treating an animal suffering a disease characterized by excessive apoptosis by administering a therapeutically effective amount of at least one serine protease inhibitor and thereafter monitoring a decrease in apoptosis. The inhibitor of the invention includes ?1-antitrypsin or an ?1-antitrypsin-like agent, including, but not limited to oxidation-resistant variants of ?1-antitrypsin, and peptoids with antitrypsin activity. The diseases treatable by the invention include cancer, autoimmune disease, sepsis neurodegenerative disease, myocardial infarction, stroke, ischemia-reperfusion injury, toxin induced liver injury and AIDS. The method of the invention is also suitable for the prevention or amelioration of diseases characterized by excessive apoptosis.

Abstract: The present invention relates to use of convertase inhibitors for the reduction of scarring during the healing of wounds and also for reducing fibrosis in the treatment of fibrotic conditions.

Abstract: Methods for prophylactically or therapeutically treating severe pneumonia involve administration of tissue factor pathway inhibitor (TFPI) or a TFPI analog to patients suffering from or at risk of developing this condition. The methods involve the use of continuous intravenous infusion of TFPI or a TFPI analog, preferably at low doses to avoid adverse side effects.

Abstract: Methods and compositions are provided which inhibit the apoptotic activity associated with oxidative stress in many disease states. According to the invention, inhibition of chemical cleavage of PKC? by caspase-3 results in reduction of apoptosis. Novel peptide inhibitors with the amino acid motif Asp Ile Pro Asp (SEQ ID NO:5) are also disclosed. The peptides are useful as inhibitors of PKC?-mediated apoptosis and oxidative stress, and other diseases regulated by a catalytically active PKC?.

Abstract: 5-mer peptides that can inhibit calpain I and calpain II are disclosed. The peptide sequence is as follows: Leu or Ala)-(Xaa)-(Asp or Glu)-(Xaa)-(Leu or Met), where Xaa can be any amino acid.

Abstract: The present invention relates to MMP regulators that comprise new synthetic peptides, that comprise amino acid sequences structurally similar to those of MMP binding region of TIMPs, coupled to zinc chelators. The invention also relates to methods for making these MMP regulators and their use for the treatment of chronic and acute wounds and for the treatment of angiogenesis-associated diseases.

Abstract: Human antithrombin variants showing a high protease inhibitory activity even in the absence of heparin wherein at least one of the amino acids at positions 78, 278, 378 and 380 in the amino acid sequence of natural human antithrombin is substituted by another amino acid. Preferable examples thereof are human antithrombin variants wherein the amino acid at position 78 is substituted by Phe; the amino acid at position 278 is substituted by Ala, Arg, Asn, Gly, His, Tyr or Val; the amino acid at position 378 is substituted by Lys, Asn or Val; and/or the amino acid at position 380 is substituted by Ala, Asp, Gly, His, lie, Leu, Asn, Pro, Arg, Thr, Tyr or Val.

Abstract: Polypeptides, in particular the polypeptide of formula I: Ala-Gln-Glu-Pro-Val-Lys-Gly-Pro-Val-Ser-Thr-Lys- Pro-Gly-Ser-Cys-Pro-Ile-Ile-Leu-Ile-Arg-Cys-Ala- Met-Leu-Asn-Pro-Pro-Asn-Arg-Cys-Leu-Lys-Asp-Thr- Asp-Cys-Pro-Gly-Ile-Lys-Lys-Cys-Cys-Glu-Gly-Ser- Cys-Gly-Met-Ala-Cys-Phe-Val-Pro-Gln and analogues thereof which possess inhibitory activity against human leukocyte elastase. The polypeptides may be obtained by expression using plasmidic expression systems in hosts such as E. Coli and yeast, the polypeptide of formula I being also obtainable from psoriatic plaques.

Abstract: The present invention discloses modified antithrombin III compounds and methods. The amino acid compounds of the present invention are useful in treating blood clotting disorders, as well as other disease states associated with enzymes in the coagulation pathway.

Abstract: The present invention provides an mbCRP capable of effectively suppressing complement activity and completely inhibiting generation of intermediates damaging a transplanted tissue during the complement activation. To be more specific, the present invention provides a membrane-bound C1 inhibitor comprising a protein containing a functional domain of a water-soluble C1 inhibitor and an anchor molecule attached to an end and/or an interior of the protein.

Abstract: Permeability of the blood-brain barrier and other physiological barriers can be modulated by the degree of tyrosine phosphorylation of proteins. Agents which promote tyrosine protein dephosphorylation reduce the permeability of the blood-brain barrier and those which promote phosphorylation increase permeability. Increasing blood-brain barrier permeability is useful in delivering drugs having a desired effect upon the central nervous system; decreasing blood-brain barrier permeability and other physiological barrier permeability is useful in preventing undesired compounds reaching the CNS and in certain clinical conditions.

Abstract: The present invention relates to novel compounds and pharmaceutical composition, their preparation, and their use, having a antithrombotic effect through reversible inhibition of activated blood coagulation factor VIIa “FVIIa”.

Abstract: Method for treatment of inflammatory and fibrotic conditions in vivo using pure rhUG is disclosed. Method for treating or preventing inflammatory or fibrotic conditions characterized by a deficiency of endogenous functional UG is also disclosed. Compositions containing pure rhUG, optionally also containing lung surfactant, and assay procedures for detection of UG-fibronectin complexes, are also provided.

Abstract: There is provided a thrombin inhibitor polypeptide and DNA(RNA) encoding such polypeptide. Also provided is a procedure for producing such polypeptide by recombinant techniques. The anti-thrombin polypeptide is used to treat various diseases where prevention of blood clotting is necessary and is of therapeutic value. The present invention also discloses a method of producing the anti-thrombin polypeptide and methods for its use as a pharmaceutical composition.

Abstract: A method for the production of Tissue Factor Pathway Inhibitor (TFPI) and Tissue Factor Pathway Inhibitor 2 (TFPI-2), and muteins thereof is disclosed wherein the protein is retained within a yeast cell during growth of the yeast cell and recovered from an insoluble fraction prepared from yeast cells containing the protein.

Abstract: This invention relates to the use of an inhibitor of an activatable metabolic enzyme, which inhibitor is bound to a high molecular weight carrier, as a molecular marker for determining the activation of this enzyme for the diagnosis of the enzyme. The invention relates in particular to the use of a thrombin inhibitor, which is bound to a high molecular weight carrier, as a molecular marker for determining clotting activation in clotting diagnosis and therapy monitoring. The invention preferably relates to the use of dextran-hirudin or PEG-coupled hirudin as a molecular marker for clotting diagnosis and therapy monitoring.

Abstract: A potent serine protease inhibitor capable of inhibiting Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is provided. The inhibitor is provided in a pharmaceutical composition for treatment of diseases where inhibition of Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is indicated.

Abstract: A synthetic DNA sequence and its genetic equivalents are disclosed which sequences are capable, when used in a recombinant DNA method, of directing production of a serine protease inibitor protein. Recombinant DNA methods for the production of serine protease inhibitor proteins are also disclosed. These methods incorporate either the synthetic DNA sequence of the present invention or natural DNA sequences isolated from human cDNA or genomic libraries.

Abstract: A potent serine protease inhibitor capable of inhibiting Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is provided. The inhibitor is provided in a pharmaceutical composition for treatment of diseases where inhibition of Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is indicated.

Abstract: A potent serine protease inhibitor capable of inhibiting Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is provided. The inhibitor is provided in a pharmaceutical composition for treatment of diseases where inhibition of Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is indicated.

Abstract: This invention relates to oxazolidine inhibitors of calpain and/or cathepsin B and to compositions containing them. As inhibitors of calpain and/or cathepsin B, the compounds are useful in the treatment of patients afflicted with acute or chronic neurodegenerative disorders.

Abstract: This invention concerns methods of treating mast-cell mediated conditions in mammals, the methods comprising administering to the mammals pharmacologically active fragments or muteins of SLPI; methods of treating asthma or allergic rhinitis in mammals, the methods comprising administering to the mammals SLPI or pharmacologically active fragments or muteins thereof; methods for inhibiting tryptase; methods for identifying inhibitors of tryptase; and certain fragments and muteins of SLPI.

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 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: Pharmaceutical composition containing Ecotin in a therapeutically effective amount for inhibition of blood coagulation.

Abstract: Peptides capable of binding calmodulin are disclosed. The peptides surprisingly do not exhibit strict .alpha.-helical conformations.

Abstract: Provided is a chimeric HV1/HV3 hirudin analog useful as an anti-coagulant, exhibiting higher anti-thrombin activity and less tendency to cause bleeding than hirudin HV1. Also provided are a method of producing hirudins and hirudin analogs, as well as other proteins, employing secretion vectors, and transformed microorganisms such as E. coli. Pharmaceutical compositions comprising various hirudins or the chimeric HV1/HV3 hirudin analog of the present invention and a pharmaceutically acceptable carrier are also disclosed.

Abstract: An isolated DNA encoding a polypeptide substantially identical to maspin (SEQ ID NO:1); a substantially purified preparation of maspin; an antibody specific for maspin; and use of such DNAs and antibodies in diagnostic, screening, and therapeutic methods.

Abstract: A novel human antithrombin III (AT III) mutant having a high antithrombin activity in the absence of heparin and effective in the treatment of thrombotic disorders as an anticoagulant, which is obtained by mutating amino acids at the reactive site and the heparin binding site of human AT III into another amino acids with the use of the recombinant DNA technology with the use of a DNA coding for AT III as a template. The invention also relates to a method for mass producing the above-described mutant by incubating a host transformed by an expression vector having the cDNA of the mutant inserted therein.

Abstract: A diagnostic composition suitable for administration to a warm-blooded animal comprising hirudin or a molecule capable of interacting with the hirudin receptor labeled with a radionuclide by means of a chelate ligand capable of administration to an animal to produce reliable visual imaging of thrombus.

Abstract: The invention provides .alpha.-1-antichymotrypsin and protein preparations comprising human .alpha.-1-antichymotrypsin produced by E. coli cells transformed with a DNA sequence encoding human .alpha.-1-antichymotrypsin. The invention also provides methods for producing .alpha.-1-antichymotrypsin. The invention further provides analogues of .alpha.-1-antichymotrypsin that exhibit antichymotrypsin, anti-trypsin and anti-thrombin activity and methods of producing the analogues.

Abstract: A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence RKPRC or analogs thereof. The cysteine residue is required for activity.

Abstract: Kunitz-type inhibitor derived from the .alpha.3-chain of human type VI collagen produced by recombinant DNA technology, variants thereof, process, expression vector and recombinant host therefore and pharmaceutical use thereof are disclosed.

Abstract: The present invention relates to novel, bifunctional inhibitors of both platelet activation and thrombin. These bifunctional inhibitors are characterized by two domains -- a glycoprotein IIb/IIIa inhibitory domain and a thrombin inhibitory domain. The invention also relates to DNA sequences which encode the bifunctional inhibitors of this invention, recombinant DNA molecules which contain these DNA sequences and host transformed with these DNA molecules. The invention further relates to he recombinant expression of the bifunctional inhibitors of this invention by transformed hosts as well as to methods for purifying such recombinant bifunctional inhibitors. This invention also provides compositions and methods employing the novel bifunctional inhibitors alone or together with a fibrinolytic agent.

Abstract: Promoters associated with expression of specific enzymes in the glycolytic pathway are used for expression of alien DNA, particularly yeast promoters known to provide high enzyme levels of enzymes in the glycolytic pathway are employed for expressing a mammalian protein, such as .alpha..sub.1 -antitrypsin. The promoters include promoters involved in expression of pyruvate kinase, triose phosphate isomerase, phosphoglucose isomerase, phosphoglycerate mutase, hexokinase 1, hexokinase 2, glucokinase, phosphofructokinase, and aldolase, as well as the glycolytic regulation gene. Particularly, the glycolytic regulation gene can be used in conjunction with promoters in the glycolytic pathway for regulated production of desired proteins.

Abstract: The protein PP4-X, whose amino acid sequence and the DNA sequence coding for this have been determined, has anticoagulative properties and can be prepared by genetic manipulation. PP4-X is used for therapeutic and diagnostic purposes.

Abstract: Hybrid proteins containing repressor proteins and substituted receptor binding sites, amino acid and DNA sequences encoding the hybrid proteins are provided. Methods for preparing the hybrid proteins are also described.

Abstract: A protein having a molecular weight of about 6,000 daltons which is biologically active in the inhibition of Factor Xa during the blood coagulation cascade, a method for producing the protein, methods for inhibiting blood coagulation using the protein, and suitable pharmaceutical compositions.

Abstract: Pharmaceutical compositions containing a 57 amino acid protease inhibitor and uses for those compositions are taught. The protease inhibitor is referred to as A4i which is associated with Alzheimer's disease. In addition to the A4i protease, other analogs are taught as are pharmaceutical compositions containing such analogs and their uses in treating a variety of abnormalities associated with Kunitz-type basic protease inhibitors. For example, it has been found that pharmaceutical compositions containing A4i protease and analogs thereof inhibit plasmin and tryptase, and also inhibit pancreatic trypsin, alpha-chymotrypsin, tissue kallikrein and serum kallikrein. In that certain diseases are associated with a general release of proteases such as trypsin, chymotrypsin and elastase into the circulatory system pharmaceutical compositions containing A4i and analogs thereof can be used in the management of such diseases.

Abstract: The present invention relates to a peptide having essentially the amino acid sequence of pancreatic secretory trypsin inhibitor (PSTI). The present invention also relates to variants of such peptide wherein one or more of the amino acids in the original sequence are replaced by other amino acids. These peptides show an advantageously modified specificity in their inhibotory action. A method of preparation of the peptides and their pharmaceutical use is also described.

Abstract: Protein having inflammatory phospholipase A.sub.2 inhibitory activity wherein said protein has a nature to be induced from cells by administration of glucocorticoid, for example, having a molecular weight of 40 K and the amino acid sequence from the N-terminal consisting of a N-terminal amino acid-Asp-Val-Pro-Ala-Ala-Asp-Leu-Ser-Asp-.