Abstract: Small, polybasic peptides are disclosed that are effective as furin inhibitors, e.g. hexa- to nona-peptides having L-Arg or L-Lys in most positions. Removing the peptide terminating groups can improve inhibition of furin. High inhibition was seen in a series of non-amidated and non-acetylated polyarginines. The most potent inhibitor identified to date, nona-L-arginine, had a Ki against furin of 40 nM. Non-acetylated, poly-D-arginine-derived molecules are preferred furin inhibitors for therapeutic uses, such as inhibiting certain bacterial infections, viral infections, and cancers. Due to their relatively small size, these peptides should be non-immunogenic. These peptides are efficiently transported across cell membranes.

Abstract: The invention concerns a novel ?-secretase, a method of partially purifying this novel ?-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel ?-secretase has an estimated molecular weight of about 32–39 kDa or 22–26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5–7.0.

Abstract: The present invention provides isolated monkey Cathepsin S proteins and isolated nucleic acid molecules such as cDNA molecules that encode these monkey Cathepsin S proteins. The present invention specifically provides, for example, isolated monkey Cathepsin S proteins and encoding nucleic acid molecules, methods of producing the monkey Cathepsin S proteins, methods of identifying and screening modulators of the monkey Cathepsin S proteins, and methods of using these modulators to treat a human disease or disorders associated with an orthologous human Cathepsin S protein.

Abstract: The ability to efficiently determine the state of enzyme expression in cells has long been desired as material to the diagnosis of disease. This invention relates to cytoenzymology, and more particularly to improved reagents for use in cell-based assays, especially those using fluorogenic substrates.

Abstract: The present invention provides a DNA encoding a Tumor Antigen Derived Gene TADG-14 protein selected from the group consisting of: (a) isolated DNA which encodes a TADG-14 protein; (b) isolated DNA which hybridizes to isolated DNA of (a) above and which encodes a TADG-14 protein; and (c) isolated DNA differing from the isolated DNAs of (a) and (b) above in codon sequence due to the degeneracy of the genetic code, and which encodes a TADG-14 protein. Also provided is a vector capable of expressing the DNA of the present invention adapted for expression in a recombinant cell and regulatory elements necessary for expression of the DNA in the cell.

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

Abstract: Disclosed is a method of expressing enzymatically-active, recombinant proteolytic tryptase in a eukaryotic host cell, expression constructs which drive the production of enzymatically-active tryptase in transformed hosts, and genetically-engineered eukaryotic host cells containing the expression constructs and which express enzymatically-active proteolytic tryptases. Uses for the proteolytic tryptases so produced are also disclosed. Also disclosed is a method of making active site mutants of proteolytic tryptases in a eukaryotic host cell, expression constructs which drive the production of the mutants in transformed eukaryotic host cells, and genetically-engineered eukaryotic host cells containing the expression constructs and which express the active-site mutated form of proteolytic tryptases.

Abstract: Novel protein C derivatives are described. These polypeptides retain the biological activity of the wild-type human protein C with substantially longer half-lives in human blood. These polypeptides will require either less frequent administration and/or smaller dosage than wild-type human protein C in the treatment of vascular occlusive disorders, hypercoagulable states, thrombotic disorders and disease states predisposing to thrombosis.

Abstract: Polynucleotide and polypeptide sequences are described. The polypeptide sequences comprise one or more of: (a) a polypeptide having the deduced amino acid sequence translated from the polynucleotide sequence in SEQ ID NO: 1 or SEQ ID NO: 5 and variants, fragments, homologues, analogues and derivatives thereof; (b) a polypeptide of SEQ ID NO: 2 and variants, fragments, homologues, analogues and derivatives thereof; (c) a polypeptide encoded by the cDNA of NCIMB 41110 and variants, fragments, homologues, analogues and derivatives thereof; or (d) a polypeptide which has at least 78% identity to (i) the polypeptide encoded by the polynucleotide of SEQ ID NO: 1 or SEQ ID NO: 5, (ii) the polypeptide of SEQ ID NO: 2, or (iii) the polypeptide encoded by the cDNA of NCIMB 41110. Such polypeptide sequences are, inter alia, useful in the prophylaxis and/or treatment of sexual dysfunction, in particular male erectile dysfunction (MED) or female sexual dysfunction (FSD), preferably female sexual arousal disorder (FSAD).

Abstract: The present invention concerns a process for the purification of EPI-HNE proteins, from the culture medium of a host strain for the expression of said proteins, comprising the steps of: (a) passing a derived part of the culture medium over an expanded bed of cationic exchange adsorbent or a mechanically and chemically inert micromembrane, in order to recover an eluate, (b) optionally conducting chromatographic separation of proteins, according to their hydrophobicity, on the resulting eluate, (c) passing the resulting eluate over a cationic exchange column, (d) optionally filtering the resulting medium such as to obtain a sterile filtrate, and optionally further comprising the step of (e) causing precipitation of EPI-HNE in a crystallised form and recovering the protein crystals.

Abstract: The invention concerns plasmin variants. Polynucleotides the disclosed plasmin variants are provided. Additionally, methods of using the plasmin polynucleotides and polynucleotides are provided herein.

Abstract: The present invention provides hepsin/46 protein, a soluble form of hepsin lacking the transmembrane region. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying molecules that interacting with the protease peptides, and methods of identifying modulators of the protease peptides.

Abstract: The invention relates to the discovery and characterization of mannan binding lectin-associated serine protease-2 (MASP-2), a new serine protease that acts in the MBLectin complement fixation pathway.

Abstract: The present invention relates to methods for purifying fibrinogen. In one aspect, the present invention relates to a method of separating fibrinogen from plasma fraction I precipitate. In another aspect, the invention relates to the purification of fibrinogen using ion exchange chromatography.

Abstract: The present invention relates to novel conjugates between polypeptide variants of protein C and a non-polypeptide moiety, such as PEG or sugar moieties. In particular, the present invention provides novel protein C conjugates having an increased resistance to inactivation by e.g. human plasma and ?1-antitrypsin. Consequently, such conjugates have an increased in vivo half-life. Preferred examples include protein C conjugates, wherein at least one additional in vivo N-glycosylation site has been introduced. The conjugates of the invention are useful for treating a variety of diseases, including septic shock.

Abstract: The invention relates to vWF cleaving entities having a molecular weight of 180 kD, 170 kD, 160 kD, 120 kD or 110 kD and an N-terminal amino acid sequence of AAGGILHLELLV (SEQ ID NO: 1), vWF cleaving complexes and methods for their production.

Abstract: The invention provides a human cysteine proteases and polynucleotides which encode those proteases. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists, as well as methods for diagnosing, treating, or preventing disorders associated with aberrant expression of cysteine proteases.

Abstract: A gram-negative bacterial cell is described that is deficient in a chromosomal gene present in a wild-type such cell which gene shares at least 80% sequence identity with the native sequence of the yfcK gene and encodes an aminopeptidase. Alternatively, a gram-negative bacterial cell is deficient in a chromosomal gene present in a wild-type such cell which gene encodes an aminopeptidase that shares at least 80% sequence identity with the native sequence of aminopeptidase b2324. Either of these types of cells, when comprising a nucleic acid encoding a heterologous polypeptide, produces an N-terminal unclipped polypeptide when it is cultured and the polypeptide recovered, with virtually no N-terminal clipped polypeptide produced as an impurity. Conversely, a method is provided for cleaving an N-terminal amino acid from a polypeptide comprising contacting the polypeptide with an aminopeptidase sharing at least 80% sequence identity with the native sequence of aminopeptidase b2324.

Abstract: There are provided a human BSSP6 serine protease and a pharmaceutical composition containing this serine protease. Also provided is an antibody to this serine protease or to a fragment thereof.

Abstract: The present invention provides the enzyme and enzymatic procedures for cleaving the ? secretase cleavage site of the APP protein and associated nucleic acids, peptides, vectors, cells and cell isolates and assays. The invention further provides a modified APP protein and associated nucleic acids, peptides, vectors, cells, and cell isolates, and assays that are particularly useful for identifying candidate therapeutics for treatment or prevention of Alzheimer's disease.

Abstract: The invention provides isolated nucleic acids molecules, designated 57316 or 33338 nucleic acid molecules, which encode ubiquitin carboxyl terminal hydrolase proteins. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 57316 or 33338 nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a 57316 or 33338 gene has been introduced or disrupted. The invention still further provides isolated 57316 or 33338 proteins, fusion proteins, antigenic peptides and anti-57316 or 33338 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: Binding polypeptides comprising specific amino acid sequences are disclosed that specifically bind ACE-2 protein or ACE-2-like polypeptides. The binding polypeptides can be used in methods of the invention for detecting, isolating, or purifying ACE-2 protein or ACE-2-like polypeptides in solutions or mixtures, or biological samples. The invention also relates to nucleic acid molecules encoding these ACE-2 binding polypeptides, vectors and host cells containing these nucleic acids, and methods for producing the same. The present invention also relates to methods and compositions for detecting, diagnosing, prognosing, preventing, treating or ameliorating a disease or disorder associated with aberrant ACE-2 or ACE-2 receptor expression or inappropriate function of ACE-2 or ACE-2 receptor, comprising use of ACE-2 binding polypeptides or fragments or variants thereof, that specifically bind to ACE-2.

Abstract: The invention provides isolated nucleic acids molecules, designated 68999 nucleic acid molecules, which encode ubiquitin carboxyl-terminal hydrolase family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 68999 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 68999 gene has been introduced or disrupted. The invention still further provides isolated 68999 proteins, fusion proteins, antigenic peptides and anti-68999 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: cDNA encoding C. elegans ?6 desaturase has been cloned and sequenced, and the ?6 desaturase amino acid sequence has been determined: The C. elegans ?6 desaturase has a surprisingly low level of sequence identity with the known borage ?6 desaturase. The C. elegans ?6 desaturase has been expressed in yeast. It and other desaturases can be cloned in host organisms (e.g. plants) and can be used to provide useful metabolites.

Abstract: Disclosed is a process for preparing agents containing virus-inactivated vitamin K-dependent plasma components as well as protein C, protein S, factors II, VII, IX and/or X as well as combinations thereof, such as, for example, PPSB preparations, wherein a source containing these components is subjected to a appropriate separation procedures, especially by using membrane-chromatographic methods.

Abstract: Here we describe the molecular identification of a cDNA encoding a novel serine protease we have termed protease T. The deduced amino acid sequence encodes a prepro form of 290 amino acids, and its alignment with other well-characterized serine proteases indicates that it is a member of the S1 serine protease family. We have found that the protease T mRNA is expressed in stomach, testis, retina, fibroblasts, spinal cord, and several regions of the brain. Protease T mRNA is also found in leukocytes and in the Jurkat (ATCC TIB-152) T cell line. Thus, this protease is potentially involved in gastric, testicular, retinal, dematological, neurological/neurodegenerative and/or immunological disorders. The protease T gene maps to human chromosome 16p13.3 which is near the tryptase locus. Enzymatically active protease T, we have generated, is amenable to further biochemical analyses for the identification of physiological substrates and specific modulators.

Abstract: The invention provides human protease associated proteins (HPRAP) and polynucleotides which identify and encode HPRAP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating or preventing disorders associated with expression of HPRAP.

Abstract: The present invention provides an isolated peptide that comprises the sequence shown in SEQ ID NO:1 or a sequence which has at least 95% identity with SEQ ID NO:1, and which has the same substrate specificity as SEQ ID NO:1. Preferred peptides include peptides having the amino acid sequences set forth in SEQ ID NO: 3, 5, and 7. The isolated peptide is useful as a dipeptidyl aminopeptidase.

Abstract: Highly purified mocarhagin, a cobra venom protease, is disclosed. Pharmaceutical compositions and therapeutic uses of the highly purified protease are also provided. Polynucleotides encoding such protease and related proteases are also disclosed.

Abstract: The invention provides human hydrolytic enzymes (HYENZ) and polynucleotides which identify and encode HYENZ. The invention also provide expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with expression of HYENZ.

Abstract: The present invention relates to a complex (tcuPA/suPAR) of the two chain urokinase plasminogen activator (tcuPA) with the soluble urokinase plasminogen activator (suPAR), to pharmaceutical compositions comprising this complex and to different uses of the compositions in the treatment and/or prevention of thrombotic events, particularly those associated with the formation of fibrin clots. In the complex (tcuPA/suPAR), the suPAR stimulates firbrinolytic activity mediated by tcuPA under physiological conditions. The complex acts preferably on freshly-formed clots and is specific to such clots.

Abstract: Here we describe the molecular identification of a cDNA encoding a novel serine protease we have termed protease T. The deduced amino acid sequence encodes a prepro form of 290 amino acids, and its alignment with other well-characterized serine proteases indicates that it is a member of the S1 serine protease family. We have found that the protease T mRNA is expressed in stomach, testis, retina, fibroblasts, spinal cord, and several regions of the brain. Protease T mRNA is also found in leukocytes and in the Jurkat (ATCC TIB-152) T cell line. Thus, this protease is potentially involved in gastric, testicular, retinal, dematological, neurological/neurodegenerative and/or immunological disorders. The protease T gene maps to human chromosome 16p13.3 which is near the tryptase locus. Enzymatically active protease T, we have generated, is amenable to further biochemical analyses for the identification of physiological substrates and specific modulators.

Abstract: The present invention relates to methods of regulating TNF activity indirectly by regulating the activity or concentration of TNF receptor releasing enzyme (TRRE). Preferably, the TRRE activity is regulated local to the site of the condition to be treated. In the case of diseases associated with elevated levels of TNF, such as rheumatoid arthritis, TRRE is administered to the site of inflammation in an amount sufficient to decrease the local levels of TNF. In the case of diseases, such as cancer, that benefit from increased levels of TNF, the level of TRRE is decreased at the disease site.

Abstract: This invention relates to newly identified polypeptides which have zinc metalloprotease activities and are referred to as IGS5, and polynucleotides encoding such polypeptides, to their use in therapy and in identifying compounds which may be stimulators and/or inhibitors which are useful in therapy, and to production of such polypeptides and polynucleotides.

Abstract: Disclosed are enzyme-activated anti-tumor and anti-metastatic prodrug compounds. The specific enzymes are collagenase(IV) and elastase. Also disclosed are methods of making and using such compounds.

Abstract: Genetically-encodable, environmentally-responsive fusion proteins comprising ELP peptides. Such fusion proteins exhibit unique physico-chemical and functional properties that can be modulated as a function of solution environment. The invention also provides methods for purifying the FPs, which take advantage of these unique properties, including high-throughput purification methods that produce high yields (e.g., milligram levels) of purified proteins, thereby yielding sufficient purified product for multiple assays and analyses. The high throughput purification technique is simpler and less expensive than current commercial high throughput purification methods, since it requires only one transfer of purification intermediates to a new multiwell plate.

Abstract: Compositions comprising a novel protease capable of cleaving ?-amyloid precursor protein (APP) on the amino-terminal side of the ?-amyloid peptide therein are provided. The protease is designated ?-secretase. Reaction systems comprising ?-secretase may be used in screening assays to monitor ?-secretase modulated cleavage of APP and to identify ?-secretase inhibitors, wherein the ?-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 ?-secretase. Pharmaceutical compositions and methods comprise compounds identified by screening assays.

Abstract: Novel human polynucleotide and polypeptide sequences are disclosed that can be used in therapeutic, diagnostic, and pharmacogenomic applications.

Abstract: Here we describe the molecular identification of a cDNA encoding a novel serine protease we have termed protease C-E. The deduced amino acid sequence, and it alignment with other well-characterized serine proteases indicates that it is a member of the S1 serine protease family. We have found that the protease C-E mRNA is expressed in pancreas, placenta, prostate, small intestine, stomach, spleen, fibroblasts and epidermis, as well as in certain regions of the brain i.e., cerebellum, cerebral cortex, pituitary and hippocampus. Enzymatically active protease C-E, as produced using the methodologies described herein, is amenable to further biochemical analyses for the identification of physiological substrates and specific modulators.

Abstract: The present invention provides a process for economically producing N-acetylneuraminic acid without using expensive materials such as pyruvic acid and phosphoenolpyruvic acid. The process comprises: allowing (i) a culture of a microorganism having N-acetylneuraminic acid aldolase activity or N-acetylneuraminic acid synthetase activity, or a treated matter of the culture, (ii) a culture of a microorganism capable of producing pyruvic acid or a treated matter of the culture, or a culture of a microorganism capable of producing phosphoenolpyruvic acid or a treated matter of the culture, (iii) N-acetylmannosamine, and (iv) an energy source which is necessary for the formation of pyruvic acid or phosphoenolpyruvic acid to be present in an aqueous medium to form and accumulate N-acetylneuraminic acid in the aqueous medium; and recovering N-acetylneuraminic acid from the aqueous medium.

Abstract: Novel proteins or polypeptides having significant sequence homology to DPPIV, nucleic acids coding therefor, cells which have been modified with such nucleic acid so as to express these proteins, antibodies to these proteins, screening methods for the discovery of new therapeutic agents which are inhibitors of the activity of these proteins or of related proteins, and therapeutic agents discovered by such screening methods, as well as new therapeutic treatments, are all provided.

Abstract: Novel human protein C derivatives are described. These derivatives have increased anti-coagulation activity and resistance to inactivation by serpins, compared to wild-type protein C and retain the biological activity of the wild-type human protein D. These derivatives will require either less frequent administration and/or smaller dosage than wild-type human protein C in the treatment of acute coronary syndromes, vascular occlusive disorders, hyper coagulable states, thrombotic disorders and disease states predisposing to thrombosis.

Abstract: The present invention features human HX2004-6 polypeptide and nucleotide sequences encoding HX2004-6 polypeptides. In a particular aspect, the polynucleotide is the nucleotide sequence of SEQ ID NO: 1. In related aspects the invention features expression vectors and host cells comprising polynucleotides that encode a human HX2004-6 polypeptide. The present invention also relates to antibodies that bind specifically to a human HX2004-6 polypeptide. Further provided are diagnostic and screening methods using HX2004-6 polynucleotides and antibodies specific for HX2004-6 polypeptides.

Abstract: There are disclosed a nucleic acid whose expression is enhanced in human neuroblastoma with unfavorable prognosis based on comparison between human neuroblastoma with favorable prognosis and human neuroblastoma with unfavorable prognosis, the nucleic acid comprising any one of base sequences set forth in SEQ ID NO:1 to NO:69 in the Sequence Listing, a nucleic acid comprising a portion of any of those base sequences, and an isolated nucleic acid capable of hybridizing to a complementary base sequence of the foregoing under stringent conditions. It discloses gene sequences relating to favorable or unfavorable prognosis of neuroblastoma and will enable the provision of their genetic information and the diagnosis of favorable or unfavorable prognosis.

Abstract: The present invention relates to a novel t-PALP protein which is a member of the serine protease family. In particular, isolated nucleic acid molecules are provided encoding the human t-PALP protein. t-PALP 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 t-PALP activity. Also provided are diagnostic methods for detecting circulatory system-related disorders and therapeutic methods for treating circulatory system-related disorders.

Abstract: A tumor necrosis factor-&agr; converting enzyme (TACE) is produced, purified, and crystallized. The three-dimensional coordinates of the crystal are obtained by X-ray diffraction. The coordinates can be recorded on a computer readable medium, or are part of a video memory, where they can be used as part of a system for studying for studying TACE. The coordinates are also used in designing, screening, and developing compounds that associate with TACE.

Abstract: The invention provides a polypeptide which encodes human presenilin variant. It also provides for the use of the cDNA and protein in the diagnosis, prognosis, treatment and evaluation of therapies for cancer or neurodegenerative or immune disorders. The invention further provides vectors and host cells for the production of the protein and transgenic model systems.

Abstract: Biomimetic gels via enzymatic preparation, using a transglutaminase to cross-link polymer-peptide conjugates of rational design.

Abstract: The present invention is based on the discovery of genetic polymorphisms that are associated with Alzheimer's disease. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

Abstract: Genomic and cDNA sequences coding for a protein having substantially the same biological activity as human protein C are disclosed. Recombinant plasmids and bacteriophage transfer vectors incorporating these sequences are also disclosed.