Abstract: The present invention relates to deletion and substitution mutant polypeptides of human chemokine &bgr;-7 (Ck&bgr;-7), as well as nucleic acid molecules encoding such polypeptides and processes for producing such polypeptides using recombinant techniques. In one aspect, the invention also relates to uses of the full-length and mature forms of Ck&bgr;-7, as well as deletion and substitution mutants, in medical treatment regimens. In particular, the Ck&bgr;-7 polypeptides described herein may be employed to treat a variety of conditions, including rheumatoid arthritis, inflammation, respiratory diseases, allergy, and IgE-mediated allergic reactions.

Abstract: The present invention provides methods to produce immunotoxins (ITs) and cytokines with a reduced ability to promote vascular leak syndrome (VLS). The invention also provides ITs and cytokines which have been mutated to lack amino acid sequences which induce VLS.

Abstract: There is disclosed a pharmaceutical composition and method for treating sepsis, including, septic shock and ARDS (acute respiratory distress syndrome), comprising administering an effective amount of a HMG1 antagonist. There is further disclosed a diagnostic method for monitoring the severity or potential lethality of sepsis or septic shock, comprising measuring the serum concentration of HMG1 in a patient exhibiting or at risk or exhibit sepsis or septic shock symptoms. Lastly, there is disclosed a pharmaceutical composition and method for effecting weight loss or treating obesity, comprising administering an effective amount of HMG1 or a therapeutically active HMG1 fragment.

Abstract: A transmucosally administerable composition with enhanced penetration comprising: about 0.001% to about 2.5% of a delivery agent selected from the group consisting of histamine, histamine dihydrochloride, histamine phosphate, a pharmaceutically acceptable salt thereof, other histamine-receptor agonists, about 0.2% to about 75% of a pharmaceutically active medicament, about 0% to about 99.8% of solvent, and about 0% to about 15% of a gelling agent.

Abstract: The present invention relates to canine interleukin-4, canine or feline Flt-3 ligand, canine or feline CD40, canine or feline CD154, canine interleukin-5, canine interleukin-13, feline interferon alpha, and/or feline GM-CSF proteins; to canine interleukin-4, canine or feline Flt-3 ligand, canine or feline CD40, canine or feline CD154, canine interleukin-5, canine interleukin-13, feline interferon alpha, and/or feline GM-CSF nucleic acid molecules, including those that encode canine interleukin-4, canine or feline Flt-3 ligand, canine or feline CD40, canine or feline CD154, canine interleukin-5, canine interleukin-13, feline interferon alpha, and/or feline GM-CSF proteins, respectively; to antibodies raised against such proteins; and to inhibitory compounds that regulate such proteins. The present invention also includes methods to identify and obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds.

Abstract: A method of treating an immunologic, proliferative, or infectious disease in a warm-blooded animal is disclosed. The method comprises administering to the animal omega interferon (IFN) at a dosage and activity for the disease state treated sufficient to induce a therapeutic response in the animal, which dosage and activity for the disease state treated is higher than would be well-tolerated based on data for non-omega IFN's. The omega IFN is administered alone or in combination with a therapeutically effective amount of at least one adjunctive therapeutic agent. Also disclosed is an article of manufacture useful for treating an immunologic, proliferative, or infectious disease, which article comprises (1) omega IFN in a form suitable for administering a therapeutically effective amount of the omega IFN to the subject in order to induce the desired therapeutic response (2) instructions for administering the omega IFN as desired, that is higher than would be well-tolerated based on data for non-omega IFNs.

Abstract: A method for producing a physiologically active polypeptide, comprising contacting a precursor polypeptide with an activating enzyme, or co-expressing the polypeptide with an activating protease.

Abstract: The present invention provides A therapeutic method to enhance the efficacy of interferon treatment comprising administering to a mammal subject to interferon treatment a compound which is an antagonist of the IL-4 or IL-13 signal transduction pathway in an amount effective to enhance said efficacy. The method includes treatment of diseases such as cancer, proliferative fibrotic diseases, viral diseases, or autoimmune diseases. The invention also includes the use of chemotherapeutic agents, radiation or other treatments in conjunction with the method of the invention.

Abstract: The present invention relates to the characterization of the porcine adenovirus E1 region. The complete nucleotide sequence of the genome of porcine adenovirus type 3 (PAV-3), providing the characterization of the PAV3 E1 region, is described herein. Methods for construction of infectious PAV genomes by homologous recombination in procaryotic cells are provided. Recombinant PAV viruses are obtained by transfection of mammalian cells with recombinant PAV genomes. The PAV-3 genome can be used as a vector for the expression of heterologous nucleotide sequences, for example, for the preparation and administration of subunit vaccines to swine or other mammals.

Abstract: This invention relates to the development of a mammalian expression vector, under which expression of the structural genes of western equine encephalitis virus have been placed under the control of an eucaryotic promoter. When the recombinant vector is administered to mammalian cell culture or using a cell-free transcription/translation system, in vitro, authentic structural proteins of western equine encephalitis virus are produced as verified by reactivity with monoclonal antibodies developed to western equine encephalitis virus. When the recombinant DNA molecule is administered in vivo, a protective immune response is induced, thereby enhancing protection of the individual against subsequent infection by western equine encephalitis virus. In a similar manner, DNA vaccines to related alphaviruses (Venezuelan and eastern equine encephalitis viruses) could also be developed.

Abstract: Disclosed is a vector containing a nucleic acid sequence encoding erythropoietin (Epo) in operable linkage with an HRE expression control sequence, as well as uses thereof; for instance, in preparing a medicament, as well as in methods for treating anemia in a patient in need thereof. The method can involve administering to the patient a vector comprising a nucleic acid sequence encoding erythropoietin (Epo) in operable linkage with an HRE expression control sequence, wherein expression of Epo is physiologically regulated such that hematocrit levels of the patient are corrected and maintained.

Abstract: The present invention relates to recombinant adenoviruses expressing interleukin-18 protein, and gene therapy using them. More particularly, the invention provides recombinant adenoviruses Ad.promIL-18, Ad.GMmIL-18, Ad.prohIL-18, Ad.hIL-18CPP32- and Ad.preprotrypsin.hIL-18CPP32- which are effectively capable of treating a variety of cancer cells by promoting and enhancing an immune response in vivo.

Abstract: Described is a process for delivering an inhibitor directed against an expressible nucleic acid sequence in a mammal to inhibit RNA function. An RNA function inhibiting sequence that is specific to the expressible nucleic acid sequence in the mammal is made and inserted into a blood vessel in the mammal. The inhibitor is delivered to a cell wherein expression of the nucleic acid sequence is inhibited.

Abstract: An alpha-lentivirus vector comprising at least one alphaviral component and at least one lentiviral component, wherein the lentiviral component is capable of being packaged into a lentiviral particle after introduction of said vector into a human cell.

Abstract: A method of treatment of an anal disease, said method including the step of increasing the level of at least one isoform of the enzyme nitric oxide synthase in the cells of the ano-rectal region of a subject in need of such treatment.

Abstract: The invention provides methods of repairing damage to, or defects in, mammalian tissues or organs. In these methods, a particulate or non-particulate acellular matrix made from a tissue or organ other than the tissue or organ being repaired is placed in or on the organ or tissue that is being repaired.

Abstract: Novel oxidative stress-resistant cell lines are provided. Such cell lines may be used to advantage in methods for the treatment neurodegenerative disorders associated with oxidative damage and subsequent neuronal cell loss, including, but not limited to, Parkinson's disease and head trauma.

Abstract: Modification of internal sites of the adenovirus fiber protein and hexon protein permit effective targeting of adenovirus vectors. Accessible sites to redirect adenovirus targeting were identified. The HVR5 loop of the hexon protein and the HI loop of the fiber protein (knob) were highly permissive for the insertion of foreign protein sequences, which apparently did not impact on the viability and productivity of corresponding viruses. Accessibility and functionality of the epitope strongly depend on the size of the neighboring spacers. Other results suggest that short targeting peptides can be effectively fused to the C-terminus of the fiber protein. In a specific embodiment, a series of adenovirus vectors modified at the HVR5 site, the fiber protein HI loop, or the fiber protein C-terminus to target urokinase-type plasminogen activator receptor bearing cells were prepared. Such vectors are particularly useful for targeting the vasculature, e.g. for gene therapy of cancers or cardiovascular conditions.

Abstract: This invention relates to lymphotoxin-&bgr;, a lymphocyte membrane type protein. This protein is found on the surface of a number of cells, including phorbol ester (PMA) stimulated T cell hybridoma II-23.D7 cells. This invention also relates to complexes formed between lymphotoxin-&bgr; and other peptides such as lymphotoxin-&agr; and to complexes comprising multiple subunits of lymphotoxin-&bgr;. These proteins and complexes are useful in holding LT-&agr; formed within the cell on the cell surface where the LT-&agr;/LT-&bgr; complex may act as an inflammation regulating agent, a tumor growth inhibiting agent, a T cell inhibiting agent, a T cell activating agent, an autoimmune disease regulating agent, or an HIV inhibiting agent. Furthermore, the antitumor activity of the LT-&agr;/LT-&bgr; complex may be delivered to tumor cells by tumor infiltrating lymphocytes (TILs) transfected with the gene for LT-&bgr;.

Abstract: The invention provides biocompatible, biodegradable calcium sulfate matrices containing calcium sulfate activated platelets for use in tissue formation. The matrices are particularly useful in stimulating hard tissue, for example, bone formation. The matrices may also further include a growth factor and/or a transfectable gene, the inclusion of which may be useful in stimulating the growth of tissue of interest.

Abstract: The invention relates to methods of modifying cells of corneal tissue to express an active agent, to modified corneal tissue, to vectors utilised in such methods and to methods of xeno- and allo-transplantation utilising the modified corneal tissue. The method of modifying cells of corneal tissue to express an active agent involves exposing harvested corneal tissue to an effective concentration for transfection of an expression vector which comprises a nucleotide sequence encoding for the active agent for a period sufficient to allow infection, such that cells of said corneal tissue will express the active agent.

Abstract: The invention provides methods for T helper-independent activation of an antigen-specific cytotoxic T lymphocyte response in an individual. The methods generally involve administering to an individual an immunostimulatory nucleic acid molecule in an amount effective to increase an antigen-specific CTL response in the individual. The invention further provides methods for increasing chemokine secretion, which can block HIV infection.

Abstract: Hydro-activated and/or oxygen activated aqueous, enzymatic, antimicrobials denture adhesive compositions are stabilized against enzymatic action prior to oral application of the adhesive by incorporating a thickener into the adhesive formulation so as to provide the forrmulation with an enzyme immobilizing viscosity which inhibits enzymatic action during processing and in the adhesive package. An illustrative, thickened, enzymatic adhesive with this enhancement contains glucose oxidase, glucose, lactoperoxidase and potassium thiocyanate together with a mixture of polyacrylic acid and polyvinylpyrrolidone in an amount to provide the adhesive with a viscosity of at least about 300,000 centipoises.

Abstract: Carbonyl stress-ameliorating agents have been provided, which contain an enzyme having a glyoxalase I activity and a carbonyl compound-reducing agent as the active ingredients. The carbonyl stress-ameliorating agents of the present invention rapidly eliminate carbonyl compounds, and thus ameliorate carbonyl induced stress conditions.

Abstract: The present invention provides chitin-binding fragments of human chitinase, fragment analogs, purified and isolated polynucleotide sequences encoding such fragments and analogs, and materials and methods for the recombinant production of human chitinase fragment products which are expected to be useful as in products for detecting chitin, binding chitin, and treating fungal infections or for development of products useful for treating the same.

Abstract: Preparations of conjugates of a receptor-binding internalized ligand and a cytocide-encoding agent and compositions containing such preparations are provided. The conjugates contain a polypeptide that is reactive with an FGF receptor, such as bFGF, or another heparin-binding growth factor, cytokine, or growth factor coupled to a nucleic acid binding domain. One or more linkers may be used in the conjugation. The linker is selected to increase the specificity, toxicity, solubility, serum stability, or intracellular availability, and promote nucleic acid condensation of the targeted moiety. The conjugates are complexed with a cytocide-encoding agent, such as DNA encoding saporin. Conjugates of a receptor-binding internalized ligand to a nucleic acid molecule are also provided.

Abstract: The present invention relates to polynucleotide and polypeptide molecules for PAR4, a novel member of the protease-activated receptor family. The polypeptides, and polynucleotides encoding them, mediate biological responses and/or cellular signaling in response to proteases. Protease cleavage of PAR4 exposes a PAR4 extracellular amino terminal portion that serves as a ligand for the PAR4 receptor. PAR4 may be used as a target in drug screening, and further used to identify proteinaceous or non-proteinaceous PAR4 agonists and antagonists. The present invention also includes antibodies to the PAR4 polypeptides.

Abstract: Provided herein are type I transmembrane serine protease 25 (MTSP25) polypeptides. Activated forms of these polypeptides and single and two chain forms of the protease domain are also provided. Methods using the polypeptides for therapeutic and diagnostic purposes are provided.

Abstract: Novel polypeptides are provided, together with methods for making and using them, and nucleic acids encoding them. These polypeptides are useful as cell surface adhesion molecules and ligands, and are useful in therapeutic or diagnostic compositions and methods.

Abstract: A method of preparing a vaccine formulation comprising at least one antigen and at least one adjuvant is described, which method is characterized in that at least one antigen is mixed with at least one adjuvant and the mixture subsequently is heat-treated at a temperature of at least 80° C. for a period of time of at least 5 minutes.

Abstract: A method for producing IgG from plasma for medical applications, comprising at least: (i′) removal of albumin resulting in an IgG fraction, (ii′) purifying IgG from an IgG fraction, which is derived from the IgG fraction obtained in step (i′), by adsorbing IgG to a cation exchanger and collecting the adsorbed IgG fraction, and (iii′) virus inactivation in an IgG fraction derived from the IgG fraction collected in step (ii′). The method is characterized in; (I) concentrating the IgG fraction obtained in step (i′), (II) adjusting pH to 4±0.1 in the IgG fraction released from the cation exchanger in step (ii′), and preferably maintaining the pH below 6.0 during the remaining steps of the method; and (III) carrying out the virus inactivation (step iii′) by using chemicals at a temperature of 30° C.±2° C. for at least 4 hours. Anticomplementary activity is typically below 1 CH50/mg immunoglobulin.

Abstract: Complement is recognized as an important, humoral defense system involved in the innate (nonspecific) recognition and elimination of microbial invaders, other foreign particles or molecules, and antigen-antibody complexes from the body. The present invention makes use of the surprising notion that the handling of lipids by the body, rather than its antimicrobial activity, is the primary and most ancient function of the complement system. Consequently, atherosclerosis as observed in disorders associated with disturbed lipid metabolism (familial combined hyperlipemia (FCHL), postprandial hyperlipidemia, hypertriglyceridemia with low levels of HDL cholesterol, and insulin resistance associated with type-II diabetes and obesity), is ascribed to either genetic or acquired defects in ancient (activatory and/or regulatory) complement components. Based on this new insight, novel preventive measures and treatment modalities of disturbed lipid metabolism are introduced.

Abstract: The present invention provides antibodies that specifically bind with a high degree of binding affinity to a native ungulate PrPC and/or a denatured ungulate PrPSc, but not to a native ungulate PrPSc. Preferred antibodies find native bovine PrPC and treated PrPSc but not native bovine PrPSc and can be used in an assay to determine if a sample is infected with infectious prions, i.e. PrPSc.

Abstract: The invention concerns anti-tissue factor (anti-TF) antibodies with enhanced anticoagulant potency, and methods and means for identifying, producing and using such antibodies. The anti-TF antibodies of the present invention are designed to bind to an epitope comprising the C-terminal macromolecular substrate binding region of TF. The invention also concerns methods of treating TF-VIIa related diseases or disorders comprising administering anti-TF antibodies alone or in combination with at least one additional anticoagulant and/or anti-platelet agent.

Abstract: Various human monoclonal antibodies that bind to human LOX-1 and inhibit the binding of in-vivo LOX-1 ligands to LOX-1, and the LOX-1-mediated incorporation of the ligands into cells, were obtained by immunizing human antibody-producing transgenic mice (created by genetic engineering) with soluble human oxidized LDL receptor (LOX-1). Furthermore, the human monoclonal antibodies were found to be effective in preventing and treating a variety of diseases.

Abstract: Human Immune Cell Cytokine-like Hormone polypeptide and DNA (RNA) encoding such polypeptide in a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for stimulating the proliferation and differentiation of stem cells of the immune system. Antagonists against such polypeptides are also disclosed. The antagonists include antibodies which may be employed as a therapeutic to treat leukemia and lymphoblastoma, may also be used as imaging agents and diagnostic agents for detecting expression levels of the protein. Also disclosed are diagnostic assays for detecting diseases related to mutations in the nucleic acid sequences and altered concentrations of the polypeptides.

Abstract: The present invention relates to the identification of MHC-I and MHC-II hTRT restricted epitopes and the use of these identified epitopes to elicit an immune response against the epitope. More particularly, the identified epitopes are administered to a subject to treat hyperproliferative diseases.

Abstract: Recombinant antibody proteins are provided that specifically bind fibroblast activation protein alpha (FAP&agr;) and comprise framework modifications resulting in the improved producibility in host cells. The invention also relates to the use of said antibodies for diagnostic and therapeutic purposes and methods of producing said antibodies.

Abstract: The invention relates to compositions and methods for treating or preventing inflammation, including rheumatoid arthritis (RA). The method comprises administering to mammals in need thereof an effective amount of a composition containing an agent that inhibits IL-1/18 combination with a TNF inhibitor.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of pain disorders. The invention further provides methods for identifying a compound capable of treating a pain disorder. In addition, the invention provides a method for treating a subject having a pain disorder characterized by aberrant 57749 polypeptide activity or aberrant 57749 nucleic acid expression.

Abstract: The present invention, based on the discovery of a new biological phenomena, provides methods and compositions for use in identifying agents that modulate the phosphorylation of survivin, the interaction between survivin and p34cdc2-cyclin B1 kinase complex, and the interaction between survivin and caspase-9. Related methods and compositions can be used to modulate survivin regulated apoptosis.

Abstract: The present invention provides vectors for expressing genomic streptavidin fusion cassettes. In the various embodiments, fusion proteins produced from these vectors are provided. In particular embodiments, fusion proteins comprising a single chain antibody and genomic streptavidin are provided as are vectors encoding the same. Also provided, are methods of using the fusion proteins of the present invention, in the absence and presence of a radiation-sensitizing agent, and in particular, the use of scFvSA fusion proteins as diagnostic markers or as a cell specific targeting agents.

Abstract: The present invention is based on the discovery of a composition that provides targeted anti-microbial effect. Specifically the composition contains a targeting moiety which recognizes a target microbial organism and an anti-microbial peptide moiety which has anti-microbial activity. In addition, the present invention provides methods of treating a microbial infection, e.g., on mucosal surfaces by using the compositions provided by the present invention.

Abstract: The present invention describes novel compounds of the formula:

Abstract: The present invention relates to novel forms and configurations of intercellular adhesion molecule (ICAM) including multimeric configurations that effectively bind to human rhinovirus and can effectively reduce HRV infectivity. When in a multimeric configuration, preferably as dimers, these proteins display enhanced binding of HRV and are able to reduce HRV infectivity as well as the infectivity of other viruses known to bind to the “major” group human rhinovirus receptor (HRR). The multimerized proteins may also be used to block tICAM interaction with lymphocyte function-associated antigen-1 (LFA-1).

Abstract: A method for preventing or for treating cancer in a mammal, where the cancer cells express at least a part of an alpha fetoprotein molecule at the cell surface. The method comprises creating an immune response in the mammal to at least part of the amino acid sequence of an alpha fetoprotein molecule, where the immune response comprises activating alpha fetoprotein peptide specific T lymphocytes against the cancer cells, and where the part of the alpha fetoprotein molecule is selected from the group consisting of residues 137-145 of SEQ ID NO:2, and residues 325-334 of SEQ ID NO:2 and a combination of the preceeding.

Abstract: Vaccine compositions useful in inducing immune protection in a host against arthritogenic peptides involved in the pathogenesis of rheumatoid arthritis are disclosed. Each vaccine composition provides antigenic dnaJp1 peptide (by including the peptide or a polynucleotide which encodes the peptide) and, optionally, other peptide fragments of the microbial dnaJ protein and/or human homologs thereof. Methods for identifying persons who are predisposed to develop rheumatoid arthritis and methods for use of the inventive vaccines are also disclosed.

Abstract: The invention relates to a hypoallergenic immunogenic molecule derived from the Phl p 6 allergen, wherein the Phl p 6 molecule has an N-terminal and/or C-terminal deletion which makes the molecule at least substantially lack IgE binding capacity. The invention also relates to a hypoallergenic immunogenic combination of molecules derived from the Phl p 6 allergen, comprising (i) a Phl p 6 molecule having an N-terminal deletion which makes the molecule at least substantially lack IgE binding capacity, and (ii) a Phl p 6 molecule having a C-terminal deletion which makes the molecule at least substantially lack IgE binding capacity, which two molecules together encompass the complete sequence of Phl p 6. The invention further relates to the use of the hypoallergenic immunogenic molecule or molecule mixture in hyposensitization and diagnosis.

Abstract: The present invention relates to chemically modified prostase derivatives, fragments and homologues thereof. Such antigens may be formulated to provide vaccines for the treatment of prostate tumours. Methods for purifying prostase protein and homologues are also provided.

Abstract: Antigen and antibody vaccine composition effective in preventing hepatitis E virus (HEV) infection are disclosed. The antigen composition includes a peptide corresponding to a carboxyl terminal end region of the capsid protein encoded by the second open reading frame 2 of the HEV genome. The composition is effective in preventing HEV infection after vaccination. The antibody composition contains an antibody effective to block HEV infection of human primary hepatocytes in culture.