Abstract: Fusion proteins of protease inhibitors are provided, in particular fusion proteins of alpha 1-antitrypsin (AAT) and a second protease inhibitor, such as secretory leukocyte protease inhibitor (SLPI) or tissue inhibitor of metalloproteases (TIMP). Polynucleotides encoding the fusion proteins, vectors comprising such polynucleotides, and host cells containing such vectors are also provided. Methods of making the fusion proteins of the invention are also provide, as well as methods of using the fusion proteins, for example to inhibit protease activity in a biological sample or in the treatment of an individual suffering from, or at risk for, a disease or disorder involving unwanted protease activity.

Abstract: The present invention provides novel polynucleotides encoding LSI-01 polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel LSI-01 polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

Abstract: Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined and were used to design substrate analogs of the natural -2 substrate that can inhibit the function of memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. The inhibition constant of OM99-2 is 1.6×10?9 M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bound to this inhibitor was used to determine the three dimensional structure of the protein, and the importance of the various residues in binding. This information is useful for designing new inhibitors to memapsin 2, for diagnosing and treating and/or preventing Alzheimer's disease.

Abstract: The present invention relates to nucleotides encoding for the production of novel regulatory proteins for Nox enzymes involved in generation of reactive oxygen intermediates that affect cell division. The present invention also provides vectors containing these nucleotides, cells transfected with these vectors, antibodies raised against these novel proteins, kits for detection, localization and measurement of these nucleotides and proteins, and methods to determine the activity of drugs to affect the biological activity of the regulatory proteins of the present invention.

Abstract: This invention provides kits, devices, and methods for the detection of antibodies that recognize one or more proteins and/or antigens from porcine reproductive and respiratory syndrome virus (PRRSV). The antibodies may be in a biological fluid of a PRRSV infected or at risk subject. The invention may be advantageously applied to both the diagnosis and prevention of PRRSV infection.

Abstract: Nucleic acid compositions encoding novel ACAT proteins, as well as the novel ACAT-2 proteins, (ACAT-2) are provided. Also provided are methods of producing the subject nucleic acid and protein compositions. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including diagnostic and therapeutic agent screening applications, as well as in treatment therapies for disease conditions associated with ACAT-2 activity, e.g., in the treatment of gall stones.

Abstract: A method for the discovery of compounds suitable for the treatment and/or prophylaxis of obesity, in which the ability of the test compounds to inhibit de novo lipogenesis in mammals and/or man is determined. The use of compounds which are capable of inhibiting de novo lipogenesis in mammals, and which are substantially free of effects directed towards the CNS, for the preparation of pharmaceutical compositions for the treatment and/or prophylaxis of obesity, as well as for the treatment and/or inhibition of obesity, are also described.

Abstract: A method for inhibiting the degradation of mammalian natriuretic peptides, in particular BNP, by using containers wherein the face coming into contact with specimens are made of silicone or plastics. This material inhibits the activation of a substance, which in turn, degrades the peptides. This method makes it possible to collect specimens for measuring natriuretic peptides stably and conveniently. Also provided is a method for measuring natriuretic peptides by using these containers.

Abstract: Bifunctional inhibitor molecules and methods for their use in the inhibition of protein—protein interactions are provided. The subject bifunctional inhibitor molecules are conjugates of a target protein ligand and a blocking protein ligand, where these two moieties are optionally joined by a linking group. In the subject methods, an effective amount of the bifunctional inhibitor molecule is administered to a host in which the inhibition of a protein—protein interaction is desired. The bifunctional inhibitor molecule simultaneously binds to its corresponding target and blocking proteins to produce a tripartite complex that inhibits the target protein—protein interaction. The subject methods and compositions find use in a variety of applications, including therapeutic applications.

Abstract: The present invention relates to the use of NAD(P)H oxidase inhibitors to increase cellular uptake of glucose and in the treatment and/or prevention of diseases caused by insulin resistance or diseases related thereto, such as type II diabetes. Specifically, the invention relates to a method for identifying an agent useful for the treatment or prophylaxis of a medical condition associated with elevated levels of blood glucose, the method comprising (i) contacting a candidate agent with a mammalian NAD(P)H oxidase or NAD(P)H oxidase complex; and (ii) determining whether said candidate agent inhibits the biological activities of the NAD(P)H oxidase or NAD(P)H oxidase complex.

Abstract: The invention relates to processes for stabilizing the activity of an enzyme, comprising mixing a phosphine or phosphite with an oxidoreductase enzyme.

Abstract: PAK4 and JIK, both of which bind to MKK7 and directly phosphorylate MKK7, were found in the present invention. The present invention provides an inhibitor of c-Jun phosphorylation caused by JNK3 and a method for inhibiting the same, and an agent for preventing and/or treating a disorder attributable to c-Jun phosphorylation caused by JNK3 and a method for preventing and/or treating the same, all of which comprise inhibiting one member selected from the following: the binding of PAK4 to MKK7, the phosphorylation of MKK7 by PAK4, the binding of JIK to MKK7, and the phosphorylation of MKK7 by JIK. Further, the present invention provides a method for identifying a compound that inhibits the binding of PAK4 to MKK7, the phosphorylation of MKK7 caused by PAK4, the binding of JIK to MKK7, or the phosphorylation of MKK7 caused by JIK, as well as the compound obtained thereby.

Abstract: The present invention is based on the findings that BACE2, a homolog of ?-secretase BACE, is able to stimulate processing of APP in a non-amyloidogenic pathway, thereby suppressing the level of A?. Accordingly, the present invention provides methods and means for the identification and use of modulators of this unique activity of BACE2 to suppress A? production. The compounds identified using the methods and means provided herein may be used as potential candidates for the treatment of Alzheimer's disease and other neurological diseases by reducing ?-amyloid deposit formation.

Abstract: In general, this invention relates to nucleic acid and amino acid sequences involved in fat metabolism regulation and the use of these sequences as targets for the diagnosis, treatment, and prevention of obesity and obesity-related diseases. In addition, the invention relates to screening methods for identifying modulators of body fat metabolism and the development of treatments for obesity and obesity-related diseases.

Abstract: Sustained hydrogen production is obtained by the culturing of a genetically-modified algae, where the ability of the chloroplasts to intake sulfate is reduced or eliminated compared to wild-type algae. The alga is cultured in a sealed environment in a liquid or solid medium that contains sulfur, and hydrogen is generated continuously. Alternatively, the algae may be cultured in the presence of bacteria that also produce hydrogen gas. The hydrogen produced can be collected and used as a clean energy source.

Abstract: Peptides that have potent PLA2-inhibitory activity are disclosed. Homology searches of known PLA inhibitory molecules were used to identify and subsequently design potent peptide molecules that can induce neuroprotective as well as anti-inflammatory effect. These peptides were shown to protect against degeneration of joints in transgenic mouse model prone to arthritis. Protection from kainate-induced excitotoxic neuronal injury was also observed using these peptides. These peptides, their analogs and derivatives have potential as neuroprotective and/or anti-inflammatory agents in a clinical setting.

Abstract: A nucleic acid encoding a protein which has an amino acid sequence according to SEQ ID NO: 2, 12, or 14, or the amino acid sequence modified by addition or deletion of one or more amino acids and/or substitution by other amino acids, and which has activity to transfer a glycosyl group to the 3?-position of anthocyanins.

Abstract: The invention provides isolated nucleic acids molecules, designated MID 4460 nucleic acid molecules, which encode novel tyrosine phosphatase family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing MID 4460 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a MID 4460 gene has been introduced or disrupted. The invention still further provides isolated MID 4460 proteins, fusion proteins, antigenic peptides and anti-MID 4460 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The present invention is directed to methods of increasing oocyte production in a mammal. More specifically, the specification describes methods and compositions for inducing follicular maturation using a PDE inhibitor. The inhibitor may be used alone at high doses. Alternatively, the follicular maturation is achieved by combining a low dose of FSH with the PDE inhibitor treatment.

Abstract: The present invention features nucleic acids and polypeptides encoding novel splice variant isoforms of acetyl-CoA carboxylase 2 (ACC2). The polynucleotide sequence of ACC2sv1 is provided by SEQ ID NO 3. The amino acid sequence of ACC2sv1 is provided by SEQ ID NO 4. The present invention also provides methods for using ACC2sv1 polynucleotides and proteins to screen for compounds that bind to ACC2sv1.

Abstract: The present invention provides isolated GPBP-interacting 90 and 130 kDa polypeptides, and portions thereof (GIP90/130 polypeptides), antibodies to the GIP90/130 polypeptides, and pharmaceutical compositions thereof. The present invention also provides isolated GIP90/130 nucleic acid sequences, expression vectors comprising the nucleic acid sequences, and host cells transfected with the expression vectors. The invention further provides methods for detecting the GIP90/130 polypeptides or nucleic acid sequences, methods for inhibiting interactions between GPBP and GIP90/130 polypeptides, between pol k76 and GIP90/130 polypeptides or aggregation of GIP90/130 polypeptides, and methods for treating patients with autoimmune disorders or cancer.

Abstract: Gamma three protease is provided, a novel aspartyl class protease that is capable of taking part in the processing of amyloid precursor protein (APP) to A? peptide. Gamma three protease may be involved in the development and/or progression of Alzheimers disease. Methods of identifying inhibitors of gamma three protease, useful in the prevention or treatment of Alzheimers disease, are disclosed.

Abstract: Methods for determining inhibitors of protein interactions are provided. The method involves evaluation of potential inhibitors that can inhibit or prevent protein interactions. The method provides for high-throughput identification of novel therapeutics that can treat a disease or disorder by inhibiting protein interactions.

Abstract: This invention relates to Thypin, a new member of the human serpin polypeptide family, methods of making Thypin polypeptides and using these polypeptides to treat various medical disorders and to methods of screening for compounds that agonize or antagonize Thypin polypeptide activities.

Abstract: The present invention relates to methods of identifying agents which modulate the activity of PIPKI?661. Methods of using such agents to prevent or treat a cell migration-mediated condition or disease in a subject are also provided.

Abstract: A phospholipase A2 inhibitor protein designated “Phospholipase Inhibitor from Python” (PIP)—formerly designated “Python Antitoxic Factor” (PAF)—is given by SEQ ID NO:2. The partial amino acid sequence for PIP was initially determined from the native protein purified from the blood serum of a non-venomous snake, Python reticulatus. The complete PIP polynucleotide sequence was obtained from a cDNA clone encoding PIP, given by SEQ ID NO:1, along with the full amino acid sequence deduced from it. Also disclosed is a recombinant protein PIP, which shows strong lethal toxin neutralizing activity similar to the native PIP, and has potent anti-inflammatory activity. Both the native and the functionally equivalent recombinant PIP are useful for the prevention or treatment of conditions such as snakebites, insect stings, and inflammatory diseases.

Abstract: The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in the periplasm of gram negative bacteria and mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the outer surface-expression of ligand fusion proteins employed with phage display.

Abstract: Chimeric flaviviruses that are avirulent and immunogenic are provided. The chimeric viruses are constructed to contain amino acid mutations in the nonstructural proteins of a flavivirus. Chimeric viruses containing the attenuation-mutated nonstructural genes of the virus are used as a backbone into which the structural protein genes of a second flavivirus strain are inserted. These chimeric viruses elicit pronounced immunogenicity yet lack the accompanying clinical symptoms of viral disease. The attenuated chimeric viruses are effective as immunogens or vaccines and may be combined in a pharmaceutical composition to confer simultaneous immunity against several strains of pathogenic flaviviruses.

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 invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides via “display-less” library screening. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in soluble form in the periplasmic space of gram negative bacteria, such as Escherichia coli, and are mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the surface-expression of ligand fusion proteins employed with phage display.

Abstract: Mutants of Kunitz domain 1 (ITI-D1) of human inter-?-trypsin inhibitor (ITI), are useful as inhibitors of human neutrophil elastase. Mutants characterized by one or more of the following substitutions (numbered to correspond to bovine pancreatic trypsin inhibitor, the archetypal Kunitz domain) are of particular interest: (a) Val15 or Ile15, (b) Ala16, (c) Phe18, (d) Pro19, (e) Arg1, (f) Pro2, and/or (g) Phe4.

Abstract: The present invention relates to methods of inducing ovulation in a female host comprising the administration of a non-polypeptide cyclic adenosine monophosphate (cAMP) level modulator to the female host. In another aspect, the invention provides for specific administration of the phosphodiesterase inhibitor prior to the luteal phase of the host's ovulatory cycle. Preferred non-polypeptide cAMP level modulators include phosphodiesterase inhibitors, particularly inhibitors of phosphodiesterase 4 isoforms.

Abstract: The present invention describes methods for producing antibody libraries, and particularly for increasing antibody library diversity by inducing mutagenesis within the CDR regions of immunoglobulin heavy or light chains that are displayed on the surface of filamentous phage particles comprising the library. The invention also describes oligonucleotides useful for increasing the library diversity, and universal light chains useful in the library production methods.

Abstract: This invention provides purified telomerase and methods of purifying it. The methods involve the use of several sequential steps, including the use of matrices that bind molecules bearing negative charges, matrices that bind molecules bearing positive charges, intermediate-selectivity matrices, methods that separate molecules based on their size, shape, or buoyant density, and by affinity purification.

Abstract: A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed in functional form at the surface of a secreted recombinant genetic display package (rgdp) containing DNA encoding the sbp member or a polypeptide component thereof, by virtue of the sbp member or a polypeptide component thereof being expressed as a fusion with a capsid component of the rgdp. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected rgdps for expression of the selected sbp members. Antibody sbp members may be thus obtained, with the different chains thereof expressed, one fused to the capsid component and the other in free form for association with the fusion partner polypeptide. A phagemid may be used as an expression vector, with said capsid fusion helping to package the phagemid DNA.

Abstract: Members of the serine protease family play a role in carefully controlled processes, such as blood coagulation, fibrinolysis, complement activation, fertilization, and hormone production. The enzymatic activity of the serine proteases is regulated in part by serpins, serine protease inhibitors. Serpin dysfunction is associated with various disorders, including emphysema, blood clotting disorders, cirrhosis, Alzheimer disease, and Parkinson disease. Zserp11 is a new member of the serine protease inhibitor family.

Abstract: In various aspects, the invention provides pharmacologic and genomic methods of inhibiting fertility in a male animal, such as human male contraception, involving the manipulation of the activity of hormone-sensitive lipase, including inhibiting the activity of a hormone-sensitive lipase in the animal. In another aspect, the invention discloses the use of hormone-sensitive lipase as a target in screening assays that may be used to identify compounds that modulate male fertility. In another aspect, the present invention identifies a condition of male infertility caused by hormone-sensitive lipase deficiency.

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: The acetylation level of a peptide is determined utilizing the fact that the changes in the acetylation level are reflected in the sensitivity of the substrate peptide to a peptidase. This method can be used for measuring activities of deacetylase and acetylase, and also enables screening for substances that influence the activity of these enzymes. The deacetylase activity can be measured by a simple procedure according to the present invention.

Abstract: There is provided a protease inhibitor and a method of inhibiting a protease selected from the group consisting of thrombin, chymotrypsin and neuropsin, by contacting the protease with an effective amount of a member of the phosphoethanolamine binding protein (PEBP) family.

Abstract: The present invention provides genomic and cDNA encoding human cytoplasmic polyadenylation element binding protein, expression vectors comprising human cytoplasmic polyadenylation element binding protein cDNA and host cells that contain the expression vectors. Also provided are recombinant human cytoplasmic polyadenylation element binding protein and polypeptides derived thereof.

Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.

Abstract: Disclosed is an assay for determining the presence and concentration of trypsin inhibitor in urine samples. The assay reagents, which may be used either in the liquid or dry states, include trypsin, a trypsin substrate and a polycarboxylic chelating agent. The inclusion of the chelating agent in the assay has been found to reduce variation in the assay results.

Abstract: This invention provides a method of preventing or treating in a subject contact dermatitis which comprises administering to the subject an amount of a compound capable of inhibiting the stem cell factor signaling pathway effective to prevent or treat contact dermatitis so as to thereby prevent or treat contact dermatitis in the subject. This invention also provides a methods of preventing or treating in a subject hyperpigmentation, asthma, cutaneous inflammation, anaphylaxis and bronchospasm, mastocytosis, tumors which express activated kit, and conception.

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: This invention provides a method of preventing or treating in a subject contact dermatitis which comprises administering to the subject an amount of a compound capable of inhibiting the stem cell factor signaling pathway effective to prevent or treat contact dermatitis so as to thereby prevent or treat contact dermatitis in the subject. This invention also provides a method of preventing or treating in a subject hyperpigmentation, asthma, cutaneous inflammation, anaphylaxis and bronchospasm, mastocytosis, tumors which express activated kit, and conception.

Abstract: Disclosed are unique methods for identifying the lowest, yet optimal, aspirin doses for patients. These methods are also characterized as having little to no aspirin-related side-effects. These methods may be used pre- as well as post-thrombotic event, and employs a patient's urinary thromboxane B2 metabolic levels (e.g., 11-dehydrothromboxane B2), to identify the patient's platelet activation level. A patient's urinary thromboxane B2 metabolic level is then used to calculate and appropriate and individualized treatment effective for utilizing platelet activation. Kits for utilizing this technique are also provided. In yet another particular aspect, the invention provides a method for utilizing a random urine sample obtained from a patient to determine whether a patient or particular individual's current dosage of aspirin is providing an adequate and appropriate level of inhibition of platelet activation levels, as compared to inhibition levels observed in individuals not taking aspirin.

Abstract: This invention relates to methods and reagents for selecting a desired protein or nucleic acid molecule by linking mRNA, with known or unknown sequences, to its translated protein to form a cognate pair. The cognate pair is selected based upon desired properties of the protein or the nucleic acid. This method also includes the evolution of a desired protein or nucleic acid molecule by amplifying the nucleic acid portion of the selected cognate pair, introducing variation into the nucleic acid, translating the nucleic acid, attaching the nucleic acid to its protein to form a second cognate pair, and re-selecting this cognate pair based upon desired properties.

Abstract: This invention relates to Thypin, a new member of the human serpin polypeptide family, methods of making Thypin polypeptides and using these polypeptides to treat various medical disorders and to methods of screening for compounds that agonize or antagonize Thypin polypeptide activities.

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.