Abstract: The present invention relates to parasite astacin metalloendopeptidase proteins, nucleic acid molecules having sequences that encode such proteins, antibodies raised against such proteins and compounds that can inhibit the activities of parasite astacin metalloendopeptidases. The present invention also includes methods to obtain such nucleic acid molecules, proteins, antibodies and inhibitors. The present invention also includes therapeutic compositions comprising such nucleic acid molecules, proteins, antibodies and inhibitors as well as their use to protect animals from disease caused by parasites, such as heartworm infection.

Abstract: A fibrinolytically active metalloproteinase polypeptide (called “novel acting thrombolytic”) which is useful for blood clot lysis in vivo and methods and materials for its production by recombinant expression are described.

Abstract: A method for producing tissue plasminogen activator (t-PA) in eukaryotic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild type DHFR with methotrexate.

Abstract: The subject invention relates to fibrin sealants. More specifically, the subject invention relates to the use of a fibrin sealant wherein a composition comprising fibrin monomer or a composition comprising noncrosslinked fibrin is utilized as a component of the fibrin sealant.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of caspase 8. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding caspase 8. Methods of using these compounds for modulation of caspase 8 expression and for treatment of diseases associated with expression of caspase 8 are provided.

Abstract: MPROT12 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing MPROT12 polypeptides and polynucleotides in therapy, and diagnostic assays for such.

Abstract: Compositions and methods are provided to reduce opioid-related symptoms in a human patient of an exorphin selected from the group consisting of a gluteomorphin and a caseomorphin, comprising a physiologically effective amount of a purified casomorphin inhibitor selected from the group consisting of a casomorphinase and a casomorphin ligand, a physiologically effective amount of a purified gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, and at least one of the group consisting of a physiologically acceptable carrier, adjuvant, excipient, buffer and diluent. In some embodiments, the compositions and methods further comprise a physiologically effective amount of an enkephalin inhibitor, preferably an enkephalinase, and a physiologically effective amount of an endorphin inhibitor, preferably an endorphinase. Preferrably the caseomorphinase is dipeptidyl peptidase IV and the gluteomorphinase is tyrosinase or phenylalaninase.

Abstract: The invention relates to novel protease-inhibitors which are obtainable from leeches. It also relates to uses thereof, for instance as a medicament, thus pharmaceutical preparations are provided, as are derivatives, mutants, genes encoding, vectors comprising and cells provided with such genes and/or vectors. In particular the invention relates to a family of proteinaceous protease-inhibitors having a molecular weight of about 5.5 kD and the following primary sequences: DDNCGGKVCSKGQLCHDGHCECTPIRCLIFCPNGFAVDENGCELPCSCKHQ, DDDCGGQVCSKGQLCVDGQCKCTPIRCRIYCPKGFEVDENGCELPCTCLQ and DGNCGGQVCSKGQLCVDGQCKCTPIRCRIYCPKGFEVDENGCELPCTCLQ. This invention also relates to HIV-inhibitors and other therapeutically interesting, low molecular weight, and low antigenic substances from leeches.

Abstract: Discussed are therapeutic approaches to the treatment of thrombolic conditions. The therapies use thrombolytically active proteins which inhibit reocclusion in the subject. The proteins are administered in two or more boli.

Abstract: This invention relates to a recombinant deoxyribonucleic acid (DNA) which can be isolated from Aspergillus soyae, characterised in that it codes for a leucine aminopeptidase (LAP) and comprises a nucleotide sequence corresponding to the nucleotide sequence given in SEQ ID NO: 1 for the mature LAP or to a nucleotide sequence derived therefrom which hybridises under stringent conditions with the nucleotide sequence given in SEQ ID NO: 1 for the mature LAP. The invention further relates to vectors and transformed host organisms, and also relates to methods of producing LAP. Enzyme products for the production of protein hydrolysates, as well as protein hydrolysates which are produced correspondingly, also form part of the invention.

Abstract: A previously unknown aspartic protease capable of cleavage of proteins by hydrolysis, referred to herein as “napsin”, has been cloned from a human liver library. Two cDNA clones have been cloned, sequenced and expressed. These encode isozymes of the protease, referred to as “napsin A” and “napsin B”. The gene has also be obtained and partially sequenced. A process for rapid purification of the enzyme using immobilized petpstatin has also been developed, and enzyme isolated from human kidney tissue. Polyclonal antibodies to the enzymes have been made which are also useful for isolation and detection of the enzyme. Similarities to other aspartic proteases, especially cathepsin D, establish the usefulness of the enzyme in diagnostic assays as well as as a protease. Either or both the amount or type of napsin expressed in a particular tissue can be determined using labelled antibodies or nucleotide probes to the napsin.

Abstract: Compositions comprising a novel protease capable of cleaving &bgr;-amyloid precursor protein (APP) on the amino-terminal side of the &bgr;-amyloid peptide therein are provided. The protease is designated &bgr;-secretase. Reaction systems comprising &bgr;-secretase may be used in screening assays to monitor &bgr;-secretase modulated cleavage of APP and to identify &bgr;-secretase inhibitors, wherein the &bgr;-secretase is in the presence of a suitable polypeptide substrate and cleavage of the substrate determined in the presence and absence of the test substance. Antibodies are raised against peptides of &bgr;-secretase. Pharmaceutical compositions and methods comprise compounds identified by screening assays.

Abstract: A size modified fibrinolytic enzyme, wherein the size of the enzyme is modified by covalent attachment of at least one large organic molecule to the enzyme.

Abstract: The invention is directed to methods for the non-radioactive labeling, detection, quantitation and isolation of nascent proteins translated in a cellular or cell-free translation system. tRNA molecules are misaminoacylated with non-radioactive markers which may be non-native amino acids, amino acid analogs or derivatives, or substances recognized by the protein synthesizing machinery. Markers may comprise cleavable moieties, detectable labels, reporter properties wherein markers incorporated into protein can be distinguished from unincorporated markers, or coupling agents which facilitate the detection and isolation of nascent protein from other components of the translation system. The invention also comprises proteins prepared using misaminoacylated tRNAs which can be utilized in pharmaceutical compositions for the treatment of diseases and disorders in humans and other mammals, and kits which may be used for the detection of diseases and disorders.

Abstract: The invention provides aminopeptidase polypeptides and DNA (RNA) encoding aminopeptidase polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing aminopeptidase polypeptides to screen for antibacterial compounds.

Abstract: A process for purifying thrombin-like proteases from snake venoms is described, which consists in freeing the proteases from impurities in three chromatographic steps: a) affinity or anion exchange, b) adsorption onto a glass matrix at alkaline pH values, and c) size exclusion gel or glass matrix at acidic pH values.

Abstract: The present invention relates to an enzyme exhibiting aminopeptidase activity, a method for producing said enzyme, an enzyme preparation containing said enzyme exhibiting aminopeptidase activity, and use of said enzyme for various industrial purposes.

Abstract: To provide an amino terminal protecting group-releasing enzyme characterized in that the enzyme possesses an activity for releasing a protecting group by acting on a peptide of which amino terminal is blocked by the protecting group, and exhibits the activity for two or more protecting groups, or a functional equivalent thereof; a DNA encoding the same; a method for producing the enzyme; a method for removing amino terminal protecting group including the step of subjecting to a reaction with the enzyme to release amino terminal protecting group; and a method for analyzing an amino acid sequence. The above enzyme is useful in the analysis of an amino acid sequence of peptides, particularly proteins and peptides, of which amino terminal is blocked by unknown protecting groups.

Abstract: The present invention describes a novel polypeptide, and methods of its use in effective thrombolytic therapy in the treatment of coronary and pulmonary thrombosis. Its use is also disclosed in vaccines to abrogate a streptococcal infection. Pharmaceutical compositions containing the novel polypeptide are included. One particular form of the novel polypeptide is streptococcal surface enolase (SEN), a specific binding protein for human plasmin and/or human plasminogen on group A streptococci that displays classical &agr;-enolase activity, i.e., it can catalyze the dehydration of D-glycerate-2-phosphate to phosphoenolpyruvate. In addition, SEN impedes the inhibition of the fibrinolytic activity of plasmin by &agr;2-antiplasmin and can bind plasminogen without preventing streptokinase from cleaving this plasmin precursor.

Abstract: The present invention relates to a novel BAIT protein which is a member of serpin superfamily which is expressed primarily in brain tissue. In particular, isolated nucleic acid molecules are provided encoding the human BAIT protein. BAIT polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of BAIT activity. Also provided are diagnostic methods for detecting nervous system-related disorders and therapeutic methods for treating nervous system-related disorders.

Abstract: Members of a novel family of polypeptides, the KUZ family, are metalloproteases involved in neuronal partitioning and neuronal development. The invention provides KUZ poylpeptides, antibodies that bind the KUZ polypeptides, KUZ encoding nucleic acids, methods for identifying cells expressing the KUZ polypeptides, methods of identifying ligands that bind to the subject proteins and methods of blocking KUZ polypeptide/ligand interactions.

Abstract: The present invention relates to polypeptides having carboxypeptidase activity and isolated nucleic acid sequences encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the nucleic acid sequences as well as methods for producing the polypeptides. The present invention further relates to methods of obtaining protein hydrolysates useful as flavor improving agents.

Abstract: The invention provides customized proteases (i.e., mutant enzymes), methods of making customized proteases, as well as methods of using customized proteases. The customized proteases of the invention are derived from the known proteases. Altered transacylation reactions include the capability to perform transacylation reactions not substantially catalyzed by the known protease or the capability to perform transacylation reactions with improved yields, or both. The methods of the invention provide for customized proteases through site specific or random mutagenesis of the active site amino acids of the known proteases. The invention also provides for methods of using the customized proteases to prepare a preselected transacylation products. The preselected transacylation products produced can be modified by substitution at the N-or C-terminal with nucleophiles such as L-amino acids, D-amino acids, amino acid amides, and radioactive amino acids.

Abstract: The catalytic active site of Factor VII is modified to produce a compound which effectively interrupts the blood coagulation cascade. The modifications render Factor VIIa substantially unable to activate plasma Factors X or IX. The invention relates to novel methods of treatment and uses of modified Factor VII for preventing or treating myocardial injury associated with post-ischemic reperfusion, for improving regional myocardial blood flow during reperfusion, and maintaining or improving vascular patency in a patient, as well as topical application of modified Factor VII at vascular sites susceptible to thrombus formation.

Abstract: The present invention relates to peptides inhibiting elastase and subtilisin activity, which are derived from Guamerin, an elastase-inhibiting protein isolated from a Korean leech, Guameri(Hirudo nipponia). Since the peptides of the invention permit their convenient synthesis and use, it can be applied for the development of elastase- and subtilisin-inhibiting agents. Also, since the dimeric peptides of the invention have strong elastase- and subtilisin-inhibiting activities, they can be more practically applied for the treatment of diseases associated with elastase and subtilisin. Moreover, all of the peptides of the invention can be safely used for human body as a potential drug, since they have relatively lower molecular weights.

Abstract: The present invention relates to isolated polypeptides having aminopeptidase activity and isolated nucleic acid sequences encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the nucleic acid sequences as well as methods for producing and using the polypeptides.

Abstract: METPRO02 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing METPRO02 polypeptides and polynucleotides in therapy, and diagnostic assays for such.

Abstract: The present invention relates to flea serine protease proteins, aminopeptidase proteins and flea cysteine protease proteins; to flea serine protease, aminopeptidase and cysteine protease nucleic acid molecules, including those that encode such proteins; to antibodies raised against such proteins; and to compounds that inhibit flea serine protease, aminopeptidase and/or cysteine protease activities. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitors. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies, and/or inhibitors as well as the use of such therapeutic compositions to protect a host animal from flea infestation.

Abstract: The present invention relates to flea serine protease proteins and flea cysteine protease proteins; to flea serine protease and cysteine protease nucleic acid molecules, including those that encode such proteins; to antibodies raised against such proteins; and to compounds that inhibit flea serine protease and/or cysteine protease activities. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitors. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies, and/or inhibitors as well as the use of such therapeutic compositions to protect a host animal from flea infestation.

Abstract: The catalytic active site of Factor VII is modified to produce a compound which effectively interrupts the blood coagulation cascade. The modifications render Factor VIIa substantially unable to activate plasma Factors X or IX. Pharmaceutical compositions of the modified Factor VII are used to treat a variety of coagulation-related disorders, including platelet deposition, vascular thrombosis, ischemic reperfusion, acute closure of a coronary artery, vascular restenosis secondary to balloon angioplasty, endarterectomy, reductive atherectomy, stent placement, laser therapy or rotablation.

Abstract: The invention provides gluS polypeptides and DNA (RNA) encoding gluS polypetides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing gluS polypeptides to screen for antibacterial compounds.

Abstract: The present invention is broadly directed to a method for reducing autodegradation of activated protein C during processing and purification. The present invention provides aqueous activated protein C solutions and an improved method of processing of such solutions, comprising conducting such processing at an ionic strength of greater than 150 mM and at a pH of about 5.5 to less than 6.3.

Abstract: The present invention relates to the field of biotechnology and concerns heat-stable prolylendopeptidase, recombinant DNA coding for heat-stable prolylendopeptidase, and processes for the production of heat-stable prolylendopeptidase and of recombinant DNA coding therefor, a host transformed with said recombinant DNA and a process for the production of said transformed host.

Abstract: The present invention relates to flea serine protease proteins and flea cysteine protease proteins; to flea serine protease and cysteine protease nucleic acid molecules, including those that encode such proteins; to antibodies raised against such proteins; and to compounds that inhibit flea serine protease and/or cysteine protease activities. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitors. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies, and/or inhibitors as well as the use of such therapeutic compositions to protect a host animal from flea infestation.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. For example, genes which are differentially expressed within and among T helper (TH) cells and TH cell subpopulations, which include, but are not limited to TH0, TH1 and TH2 cell subpopulations are identified. Genes are also identified via the ability of their gene products to interact with gene products involved in the differentiation, maintenance and effector function of such TH cells and TH cell subpopulations. The genes identified can be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds as treatments of immune disorders, especially TH cell subpopulation-related disorders.

Abstract: A purified enzyme-I is obtained that participates in C-terminal amidation by acting on a peptide C-terminal glycine adduct to form a peptide C-terminal .alpha.-hydroxyglycine adduct. The enzyme has an optimum pH of about 5 to 7, an optimum temperature of 25 to 40.degree. C. and a molecular weight of about 25 kDa or about 36 kDa, and metal ions and ascorbic acid act as a cofactor. A purified enzyme-II is obtained that participates in C-terminal amidation by acting on the peptide C-terminal .alpha.-hydroxyglycine adduct to produce a C-terminal amidated compound. The enzyme has an optimum pH of about 5 to 6, an optimum temperature of 15 to 35.degree. C. and a molecular weight of about 40 kDa or about 43 kDa. Enzyme-I does not act on the peptide C-terminal .alpha.-hydroxyglycine adduct and enzyme-II does not act on the peptide C-terminal glycine adduct. The enzymes may be purified from a biological material such as horse serum by affinity chromatography using a peptide C-terminal glycine adduct as a ligand.

Abstract: The present invention relates to flea serine protease proteins, aminopeptidase proteins and flea cysteine protease proteins; to flea serine protease, aminopeptidase and cysteine protease nucleic acid molecules, including those that encode such proteins; to antibodies raised against such proteins; and to compounds that inhibit flea serine protease, aminopeptidase and/or cysteine protease activities. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitors. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies, and/or inhibitors as well as the use of such therapeutic compositions to protect a host animal from flea infestation.

Abstract: A novel method for controlled release of compounds having antimicrobial activity and a novel coating composition capable of controlled release of compounds having antimicrobial activity is provided.This invention relates to a method for releasing a compound having antimicrobial activity from a matrix at a controlled rate, which comprises incorporating an enzyme and a substrate in said matrix beforehand to allow said enzyme and said substrate to react with each other in said matrix to thereby produce said compound having antimicrobial activity; and further relates to a coating composition comprising a film-forming resin, an enzyme, and a substrate, said enzyme being capable of reacting with said substrate to produce a compound having antimicrobial activity.

Abstract: A novel 54 kDa human macrophage metalloelastase (HME) having elastolytic activity and the cDNA which encodes for this enzyme are disclosed.

Abstract: The invention relates to the use of mixtures of defined composition of purified enzymes from Clostridium histolyticum for obtaining, in a reproducible, standardized manner, cells or tissue fragments from human or animal tissues, and to these enzymes and mixtures thereof; in addition it relates to the direct or indirect medical use of these enzymes, alone or as ingredient of mixtures, eg. in wound treatment.

Abstract: The present invention provides a cyclic lipopeptide acylase which may effectively deacylate the acyl side chain of a cyclic lipopeptide compound, specifically FR901379 Substance or its analog thereof shown by the following general formula [I], and a process for production of a cyclic peptide compound which comprises the use of said acylase.

Abstract: The subject invention pertains to new thermostable enzymes and the use of these enzymes both in proteolysis as well as protein and polypeptide synthesis. The subject invention further concerns polynucleotide sequences which encode the enzymes of the subject invention.

Abstract: The present invention relates to an enzyme exhibiting aminopeptidase activity, a method for producing said enzyme, an enzyme preparation containing said enzyme exhibiting aminopeptidase activity, and use of said enzyme for various industrial purposes.

Abstract: Nucleic acids encoding various proteases, from a mammal, reagents related thereto, including specific antibodies, and purified proteins are described. Methods of using said reagents and related diagnostic kits are also provided.

Abstract: The present invention provides a t-PA medicinal preparation obtained by remarkably improving the solubility and stability of t-PA or modified t-PA. Nicotinamide or a derivative thereof is incorporated into t-PA or modified t-PA-containing solvent system. If necessary, a citrate buffer solution is also used. The t-PA-containing medicinal composition is in the form of, for example, a freeze-dried preparation.

Abstract: Conjugates of a cell targetting molecule and a mutant human carboxypeptidase A enzyme are provided. Suitable targetting molecules include antibodies, hormones, ligands, cytokines, antigens, oligonucleotides and peptidomimetics. Enzymes comprising a mutant human carboxypeptidase A enzyme are also provided.

Abstract: The invention provides isolated nucleic acid compounds encoding FtsH of Streptococcus pneumoniae. Also provided are vectors and transformed host cells for expressing the encoded protein, and a method for identifying compounds that bind and/or inhibit said protein.

Abstract: The invention is based on the finding the furin belongs to a family of endoproteolytically active enzymes and relates to a process in the in vitro cleavage of a protein by treating the protein in the presence of a Ca.sup.2+ ions with furin, or an endoproteolytically active fragment, derivative or fusion protein of furin. The invention can be used for the (micro) biological production of a protein by culturing genetically engineered cells expressing a pro-form of the protein as well as furin and isolating the protein formed. The invention also relates to a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers, diluents or adjuvants, as well as an endoproteolytically active amount of furin, or a fragment or derivative of furin having an endoproteolytic activity.

Abstract: Chimeric proteins with fibrinolytic and thrombin-inhibiting properties having a plasminogen-activating amino acid sequence which is linked at its C-terminal end to a thrombin-inhibiting amino acid sequence.

Abstract: An aminopeptidase is provided which efficiently decomposes a low-molecular-weight peptide containing glutamic acid or aspartic acid in its sequence. A method of hydrolyzing a peptide or protein by use of the aminopeptidase is also provided. Aminopeptidase GX is derived from germinated soybean cotyledons and releases glutamic acid or aspartic acid from a peptide or protein containing glutamic acid or aspartic acid at the N-terminal end and is used to hydrolyse peptides or proteins.