Abstract: This invention describes a factor Xa analog which has a substitution of a minimum of one of the amino acid between Glu226 and Arg234 and possibly Ile235, relative to the amino acid numbering according to FIG. 1, a preparation containing the activated form of the factor X analog, and a method for the production of these molecules.

Abstract: The invention features novel polypeptides homologous to the first Kunitz domain (K1) of lipoprotein associated coagulation inhibitor (LACI) that are capable of inhibiting plasmin, and nucleic acids encoding these proteins. The invention also features the use of such polypeptides in diagnostic, therapeutic and clinical methods.

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 modulator include phosphodiesterase inhibitors, particularly inhibitors of phosphodiesterase type 4.

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 novel metalloproteinase inhibitor, analogs thereof, polynucleotides encoding the same, and methods of production, are disclosed. Pharmaceutical compositions and methods of treating disorders caused by excessive amounts of metalloproteinase are also disclosed.

Abstract: The present invention provides nucleic acid and amino acid sequences of acetyl CoA synthetase (ACS), plastidic pyruvate dehydrogenase (pPDH), ATP citrate lyase (ACL), Arabidopsis pyruvate decarboxylase (PDC), and Arabidopsis aldehyde dehydrogenase (ALDH), specifically ALDH-2 and ALDH-4. The present invention also provides a recombinant vector comprising a nucleic acid sequence encoding one of the aforementioned enzymes, an antisense sequence thereto or a ribozyme therefor, a cell transformed with such a vector, antibodies to the enzymes, a plant cell, a plant tissue, a plant organ or a plant in which the level of an enzyme has been altered, and a method of producing such a plant cell, plant tissue, plant organ or plant. Desirably, alteration of the level of enzyme results in an alteration of the level of acetyl CoA in the plant cell, plant tissue, plant organ or plant.

Abstract: The present invention provides novel nucleic acid molecules coding for sigma subunits of Mycobacterium tuberculosis RNA polymerase. It also relates to polypeptides, referred to as SigA and SigB, encoded by such nucleic acid molecules, as well as to vectors and host cells transformed with the said nucleic acid molecules. The invention further provides screening assays for compounds which inhibit the interaction between a sigma subunit and a core RNA polymerase.

Abstract: The invention provides a two new human DnaJ-like proteins (HSPJ1 or HSPJ2) and polynucleotides which identify and encode HSPJ1 or HSPJ2. The invention also provides expression vectors, host cells, agonists, antibodies and antagonists. The invention also provides methods for treating disorders associated with expression of HSPJ1 or HSPJ2.

Abstract: Compounds that inhibit ubiquitin-mediated proteolysis of phosphorylated I?B by interfering, directly or indirectly, with the ability of ?-TrCP/E3RS to engage in protein-protein association involving hnRNP-U, are useful as drugs for treating conditions associated with NF-?B activation. Cellular and non-cellular screening methods for identifying such compounds are based on monitoring the association/dissociation of ?-TrCP/E3RS.

Abstract: Analogues of the Kunitz Protease Inhibitor (KPI) domain of amyloid precursor protein bind to and inhibit activity of serine proteases, including kallikrein, plasmin and coagulation factors such as factors VIIa, IXa, Xa, XIa, and XIIa. Pharmaceutical compositions containing the KPI analogues, along with methods for using such compositions, are useful for ameliorating and treating clinical conditions associated with increased serine protease activity, such as blood loss related to cardiopulmonary bypass surgery. Nucleic acid sequences encoding these analogues and systems for expression of the peptides of the invention are provided.

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: A method is provided for the quantitative determinations of active and inactive concentrations of proteinase inhibitors, such as ?1PI and ?2M, in the body fluids of humans and animals.

Abstract: This invention involves a process for selecting and producing eukaryotic alkaline phosphatase in yeast. Yeast cells are subjected to multiple transformations using a vector comprising a first resistance marker gene and the alkaline phosphatase gene. Those strains that grow in media containing the first resistance marker are further transformed using a vector comprising a second selection marker gene and the alkaline phosphatase gene. Transformants that grow in media containing the second selection marker are selected for expressing the eukaryotic alkaline phosphatase.

Abstract: A method of identifying a compound which modulates the interaction between a PP1c and a regulatory subunit thereof, the method comprising determining whether a compound enhances or disrupts the interaction between (a) a PP1c or a fragment, variant, derivative or fusion thereof or a fusion of a fragment, variant or derivative and (b) a regulatory subunit which is able to bind to PP1c or a PP1c-binding fragment, variant, derivative or fusion of the subunit or a fusion of the fragment, variant or derivative. A method of affecting cellular metabolism or function, the method comprising administering to a cell (a) a compound which modulates the interaction between a PP1c and a regulatory subunit thereof or (b) a compound which mimics the effect of a regulatory subunit of PP1c or (c) a peptide capable of binding a PP1c and which affects the ability of PP1c to bind to a particular target and/or affects the regulation of PP1c activity, or a functional equivalent thereof.

Abstract: The invention provides a fusion protein including a reporter polypeptide, a linker polypeptide comprising a protease cleavage site, and a repressor polypeptide. The repressor polypeptide represses the activity of the reporter polypeptide by conferring a specific localization in a cell that reduces activity of the reporter activity until the cleavage site is cleaved. A method is also provided for identifying a protease that recognizes a specific protease cleavage site. The invention further provides a method of identifying a compound that activates a protease.

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

Abstract: Polypeptide and polynucleotide vaccines effective to treat or prevent infection of a mammal, such as a dog, a cat, or a human, by a protozoan. Methods of treatment and prevention are also provided, including therapeutic administration of the vaccine to an infected mammal to prevent progression of infection to a chronic debilitating disease state. Preferred embodiments of the polynucleotide vaccine contain nucleotide coding regions that encode polypeptides that are surface-associated or secreted by T. cruzi. Optionally the efficacy of the polynucleotide vaccine is increased by inclusion of a nucleotide coding region encoding a cytokine. Preferred embodiments of the polypeptide vaccine include immunogenic peptides that contain membrane transducing sequences that allow the polypeptides to translocate across a mammalian cell membrane.

Abstract: Disclosed is a pO157 plasmid-specified polypeptide found in E. coli EDL933and other enterohemorrhagic E. coli that binds to and cleaves C1-esterase inhibitor. Also disclosed are methods employing the polypeptide for diagnosing and treating colitis or hemolytic uremic syndrome, and methods of detecting potential therapeutics.

Abstract: Methods and pharmaceutical compositions are provided to prevent retroviral infections of host cells. More particularly, the invention relates to prevention of HIV infection of human cells by serine leukocyte protease inhibitor (SLPI).

Abstract: The present invention provides novel human PDE10 polypeptides, polynucleotides encoding the polypeptides, expression constructs comprising the polynucleotides, host cells transformed with the expression constructs; methods for producing PDE10 polypeptides; antisense polynucleotides; and antibodies specifically immunoreactive with the PDE10 polypeptides. The invention further provides methods to identify binding partners of PDE 10, and more particularly, binding partners that modulate PDE10 enzyme activity.

Abstract: The use of an assay for adenylate kinase in an in vitro test for the effect of external conditions on the growth characteristics of bacterial cells. Such tests in particular include tests for the sensivity of a bacteria to an antibiotic or a biostatic agent, and tests to assess the growth stage and health of the bacteria. Methods of carrying out these tests and kits for effecting them are also described and claimed.

Abstract: The present invention relates to compounds that are capable of modulating CD154 mobilization and that are useful for stabilizing the thrombotic process and reducing the activation of cells involved in an inflammatory response. The present invention also relates to methods useful for identifying such compounds. The present invention also relates to the treatment of platelets for transfusion with metalloproteinase inhibitors to treat or prevent inflammation. The present invention also includes compositions and methods to treat injury and disease related to such biological processes.

Abstract: The invention relates to the use of nucleic acids which code for plant polypeptides with the biological activity of very long chain fatty acid elongases and to the use of the polypeptides encoded thereby for identifying novel, herbicidally active compounds, and to methods for finding modulators of these polypeptides.

Abstract: The present invention is based on the identification of a series of virulence genes in E. coli K1, the products of which may be implicated in the pathogenicity of the organisms. The identification of the genes allows them, or their expressed products, to be used in a number of ways to treat infection.

Abstract: The invention relates to genetic approaches to supply nucleotide sequences encoding modified forms of the native forms of apolipoprotein A-I (ApoA-I): mature ApoA-I, preproApoA-I and proApoA-I; including native ApoA-I modified to contain ApoA-I agonists, peptides which mimic the activity of ApoA-I; ApoA-I superagonists, peptides which exceed the activity of native ApoA-I; and modified native ApoA-I having one or more amphipathic helices replaced by the nucleotide sequences of one or more ApoA-I agonists; for the treatment of disorders associated with dyslipoproteinemia, including cardiovascular disease, atherosclerosis, restenosis, hyperlipidemia, and other disorders such as septic shock.

Abstract: The present invention relates to compounds that inhibit the activity of the proteasome or the productions of proteasomal proteins and promote bone formation and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgey, and post-dental implantation, in subject where this is desirable.

Abstract: Disclosed are human interleukin-1 &bgr; converting enzyme like apoptosis proteases-3 and 4 and DNA (RNA) encoding such polypeptides. Also provided is a procedure for producing such polypeptides by recombinant techniques and antibodies and antagonists against such polypeptides. Also provided are methods of using the polypeptides, for example, as an antitumor agent, and antiviral agent, and antibodies and antagonists against such polypeptides for example, for treating Alzheimer's disease, Parkinson's disease, rheumatoid arthritis and head injury. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention for detecting diseases are also disclosed.

Abstract: Recombinant lentiviruses and transfer vectors for transgene delivery as well as methods for gene therapy using such vectors are disclosed. The invention provides a third generation lentiviral packaging system and a set of vectors for producing recombinant lentiviruses, as well as novel tissue specific enhancer and promoter elements useful for optimizing liver specific transgene delivery. The transgene is preferably a blood clotting factor such as human factor IX (hFIX) or human factor VIII (hFVIII) and can be used for treatment of hemophilia.

Abstract: The present invention provides isolated DNA molecules comprising a DNA segment encoding novel human Kunitz-type inhibitors. Also provided are DNA constructs comprising a first DNA segment encoding a novel human Kunitz-type inhibitor wherein said first DNA segment is operably linked to additional DNA segments required for the expression for the first DNA segment, as well as host cells containing such DNA constructs and methods for producing proteins from the host cells.

Abstract: Aldose redcutase inhibitor and pharmaceutically acceptable derivatives thereof of the formula I below derived from cultures of Aspergillus niger CFR 1046 and useful as a rat lens aldose reductase inhibitor

Abstract: The present invention provides a method for the measurement of an analyte in biological samples whereby an uncompetitive inhibitor is coupled to a ligand and utilized in a homogeneous assay. The analyte can be a drug or drug derivative, hormone, polypeptide, or oligonucleotide. The present invention also provides novel compounds, assay reagents and packaged kits useful for performing such measurements.

Abstract: A method is provided for nucleic acid amplification with enhanced sensitivity. The method for enhanced sensitivity involves carrying out the amplification reaction in the presence of gellan. For instance, the method allows for the production of detectible amounts of PCR amplified DNA from at least 10 fold fewer target molecules than a comparable PCR reaction in absence of gellan.

Abstract: A novel transcriptional regulatory element which was isolated from the MnSOD gene and which exhibits promoter-enhancer activity is disclosed. The promoter-enhancer activity of the element is further modulated by inflammatory mediators to regulate transcription. Methods of using the promoter-enhancer element to regulate gene expression, and therapeutic uses involving the promoter-enhancer element are also described.

Abstract: The present inventors have discovered that chorismate mutase and chorismate synthase are essential for plant growth. Specifically, the inhibition of chorismate mutase or chorismate synthase gene expression in plant seedlings results in severe chlorosis, reduced growth and developmental abnormalities. The inventors have proven that chorismate synthase and chorismate mutase can be used as targets for the identification of herbicides. Thus, the invention provides methods for the identification of chemicals that modulate chorismate synthase and chorismate mutase biochemical reactions. The methods of the invention are useful for the identification of herbicides and for the inhibition of plant growth and development.

Abstract: The present invention provides compounds which inhibit serine protease activity of matriptase or MTSP1. Also provided are pharmaceutical compositions comprising those compounds and methods of using the compounds and pharmaceutical compositions to treat conditions ameliorated by inhibition of matriptase or MTSP1. The invention provides recombinant serine protease domains and methods of using peptides comprising a recombinant serine protease domain to screen for compounds that inhibit serine protease activity of matriptase or MTSP1.

Abstract: The present invention describes a novel gene encoding a novel protein termed headpin (for head and neck serpin) that is homologous to known serine protease inhibitors. The invention describes methods and compositions of the nucleic acids, encoded proteins, antibodies, pharmaceuticals, cancer treatments, diagnostics and screens for modulators of headpin.

Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21ras. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme.

Abstract: An adenoviral vector is described which carries a codon-optimized gag gene, along with a heterologous promoter and transcription terminator. This viral vaccine can effectively prevent HIV infection when administered to humans either alone or as part of a prime and boost regime also with a vaccine plasmid.

Abstract: This invention provides methods for the discovery of molecules that target an essential step of bacterial DNA replication—the sealing of DNA strands by NAD+-dependent DNA ligase. Specific structural components of NAD+-dependent DNA ligase that are important for the reaction of DNA ligase with NAD+ and that comprise a putative binding site for the NMN component of NAD+ were identified. The invention also includes recombinant DNA ligase enzymes that are defective in their reaction with NAD+, but active in the ligation of pre-adenylated DNA nicks. An underlying principle of this invention is the use of NAD+-reactive and NAD+-defective ligases to identify molecules that specifically bind to the NAD+-binding site of DNA ligase and thereby interfere with the reaction of DNA ligase with NAD+.

Abstract: Processes for determining whether a test substance contains lipases or lipase inhibitors are provided. Processes for determining the activity of lipases or lipase inhibitors are also provided. Furthermore, processes for the preparation of micelle or vesicle substrates comprising monoacylglyceride having a fluorescent label are described.

Abstract: Chimeric proteins possessing Kunitz-type domain 1 of TFPI-2 and Kunitz-type domain 2 of TFPI are disclosed, as are muteins of TFPI and TFPI-2. Nucleic acid sequences, expression vectors and transformed host cells encoding and capable of producing the disclosed chimeric proteins and muteins are also disclosed. Finally, methods for prevention and treatment of septic shock using the chimeric proteins and muteins are disclosed.

Abstract: A family of p53 tumor suppressor nucleic acid and protein isolated from several insect species is described. The p53 nucleic acid and protein can be used to genetically modify metazoan invertebrate organisms, such as insects and worms, or cultured cells, resulting in p53 expression or mis-expression. The genetically modified organisms or cells can be used in screening assays to identify candidate compounds that are potential pesticidal agents or therapeutics that interact with p53 protein. They can also be used in methods for studying p53 activity and identifying other genes that modulate the function of, or interact with, the p53 gene. Nucleic acid and protein sequences for Drosophila p33 and Rb tumor suppressors are also described.

Abstract: Disclosed is substantially pure DNA encoding mammalian IAP polypeptides; substantially pure polypeptides; and methods of using such DNA to express the IAP polypeptides in cells and animals to inhibit apoptosis. Also disclosed are conserved regions characteristic of the IAP family and primers and probes for the identification and isolation of additional IAP genes. In addition, methods for treating diseases and disorders involving apoptosis are provided.

Abstract: The present invention relates to a novel polypeptide having a cell death inhibitory activity and use thereof, etc.

Abstract: The present inventors have discovered that serine acetyltransferase (SAT) is essential for plant growth. Specifically, the inhibition of SAT gene expression in plant seedlings results in reduced growth and altered pigmentation. Thus, SAT is useful as a target for the identification of herbicides. Accordingly, the present invention provides methods for the identification of herbicides by measuring the activity of an SAT in the presence and absence of a compound, wherein an alteration of SAT activity in the presence of the compound indicates the compound as a candidate for a herbicide.

Abstract: Disclosed herein are novel composition and methods for altering the proliferation of a cell. Included are wild-type and mutant hKIS polypeptides along with cyclin kinase inhibitors containing mutations that prevent their inhibition with serine/threonine kinases.

Abstract: Polypeptides that can modulate SIRP&agr;-CD47 functions and methods of use of the polypeptides are presented. In addition, polynucleotides that encode the polypeptides referred to above are presented. Further, pharmaceutical compositions to treat conditions are presented.

Abstract: The present invention provides molecules including Pin2 and telomerase binding polypeptides, polynucleotides encoding such polypeptides, and antibodies specifically immunoreactive to said polypeptides. The invention also provides methods for screening agents which modulate the function or expression of said Pin2 and telomerase binding polypeptides. Methods are provided for disease diagnosis and treatment using said agents, said antibodies and oligonucleotides derived from the above polynucleotides.

Abstract: The present invention relates to novel antiproliferative genes. More specifically, isolated nucleic acid molecules are provided encoding the human B-cell translocation genes 2 and 3 (BTG-2 and BTG-3). BTG-2 and BTG-3 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same.

Abstract: This invention generally relates to the nucleic acid sequences of a novel gene FAIM that encodes an apoptosis inhibiting protein. Furthermore, this invention relates to methods of identifying and testing antagonists of FAIM activity and screening for inter- and intra-specific homologs and mutants of FAIM.