Abstract: A method for pharmacological treatment of cancer and other diseases is presented which includes the novel combination of a statin (Hmg-CoA reductase inhibitor, such as lovastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, pravastatin, or newer agents), with an interferon (such as interferon alfa-2b or others) or an angiogenesis inhibitor (a very similar and often overlapping group of drugs which inhibit blood vessel growth and maintenance, such as thalidomide, angiostatin, endostatin, or other agents), and also including concurrent administration of selenium and calcium. The method disclosed in this invention is useful because it can prove more effective than previously known therapies for certain diseases and because its use may be more tolerable, less disfiguring, and less expensive than other methods. The method here disclosed can be readily reproduced by any person skilled in the art of treating disease.

Abstract: D-Ribose and methods for using D-Ribose are provided for enhancing the immune response in mammals. Those with a less than optimal immune response will benefit from oral or parenteral administration of D-Ribose. Methods are also provided for the enhancement of the immune response in isolated leukocytes. Leukocytes are cultured ex vivo in the presence of D-Ribose and transfused into a patient in need of leukocyte augmentation.

Abstract: Modified fusion proteins of transferrin and therapeutic proteins or peptides including soluble toxin receptors, with increased serum half-life or serum stability are disclosed. Preferred fusion proteins include those modified so that the transferrin moiety exhibits no or reduced glycosylation, binding to iron and/or binding to the transferrin receptor.

Abstract: The present invention relates to a composition for inhibiting tumor growth, which comprises a tumor growth inhibiting enzymatic moiety in association with at least one protective carrier. The present invention further relates to the methods of inhibiting tumor growth using this composition.

Abstract: A process for producing parenterally administrable microparticles, in which an at least 20% by weight aqueous solution of purified amylopectin-based starch of reduced molecular weight is prepared, the solution is combined with biologically active substance, an emulsion of starch droplets is formed in an outer phase of polymer solution, the starch droplets are made to gel, and the gelled starch particles are dried. A release-controlling shell is optionally also applied to the particles.

Abstract: The subject invention concerns an effective therapy for asthma, including allergic disease, using cytokine gene expression therapy. The subject invention further pertains to the use of adenovirus-medicated IFN-&ggr;(Ad-IFN-&ggr;)gene transfer to prevent or treat allergic disease and asthma, including associated conditions such as allergen-induced airway inflammation and airway hyperresponsiveness. The subject invention includes a method for effectively attenuating allergen-induced airway inflammation and airway hyperresponsiveness by administering to the respiratory tract Ad-IFN-&ggr;, to affect IL-12 and Stat-4 levels. The subject invention also provides compositions for gene therapy for asthma by the transfer of IFN-&ggr;.

Abstract: The present invention can be used in pharmacology specifically in the preparation of interferon-containing compositions, which are capable of conserving their biological activity and can be administrated intranasally, e.g. in the preparation of nasal drops. This invention essentially refers to an antiviral agent in the form of nasal drops that contains a genetically engineered alpha, beta or gamma interferon with a viscosity of (1.1-30.0)* 10 Pascal ·second, a biocompatible polymer and a buffer mixture. The agent may further include an antioxidant, and the ingredients are contained in the following amounts per ml buffer mixture: 1,000 to 5,000 IU of genetically engineered interferon; 0.005 to 0.714 g of biocompatible polymer; and 0.0001 to 0.0008 g of an antioxidant. TRILON B® (disodium salt of EDTA) is used as the antioxidant, whereas polyvinylpyrrolidone and/or polyethylene oxide is (are) used as the biocompatible polymer(s) at polyvinylpyrrolidone/polyethylene oxide ratio of 1:1-50.

Abstract: Interferons represent an important class of biopharmaceutical products, which have a proven track record in the treatment of a variety of medical conditions, including the treatment of certain autoimmune diseases, the treatment of particular cancers, and the enhancement of the immune response against infectious agents. To date, five types of interferons have been found in humans: interferon-&agr;, interferon-&bgr;, interferon-&ggr;, interferon-&ohgr;, and interferon-&egr;. The present invention provides a new form of human interferon, “Zinf2,” which has applications in diagnosis and therapy.

Abstract: Antisense oligonucleotides are provided which are complementary to and hybridizable with at least a portion of HCV RNA and which are capable of inhibiting the function of the HCV RNA. These oligonucleotides can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus, and for diagnosis and detection of HCV and HCV-associated diseases. Methods of using these compounds are also disclosed.

Abstract: The present invention relates to nucleic acid molecules that modulate Hepatitis B virus (HBV) gene expression and HBV replication, and methods thereof. Specifically, the present invention relates to nucleic acid decoy molecules and aptamers that bind to HBV reverse transcriptase and/or HBV reverse transcriptase primer sequences and methods for their use alone or in combination with other therapies. The present invention also relates to nucleic acid molecules that specifically bind the Enhancer I region of HBV DNA and methods for their use.

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 invention relates to interferon compositions, such as pharmaceutical interferon compositions and methods of their preparation. In particular it relates to stabilized compositions comprising an interferon molecule and a sulfoalkyl ether cyclodextrin derivative.

Abstract: The present invention relates to a process for ameliorating or preventing diseases that are caused, in part, by an increased level of, and/or an abnormal responsivity to, interferon. Alzheimer's disease, HIV infection, Down syndrome, transplant rejection, autoimmune disease, and infant encephalitis are examples of such diseases. Specifically, the invention provides a method for treating subjects suffering from, or at risk for, such diseases by the administration of a pharmacological preparation of interferon binding proteins of mammalian and/or viral origin that antagonize interferon's action. This invention comprises compositions of interferon binding proteins that can inhibit the activity of interferon gamma plus interferon alpha such compositions along with their method of production and modification being described herein.

Abstract: An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Methods and uses for the antibodies, optionally in combination with various therapeutic agents, are detailed, including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

Abstract: The volume of an intracranial glioma tumor is decreased by contacting the tumor with both LPS and IFN&ggr;. This protocol resulted in the eradication of detectable tumors in animal subjects.

Abstract: When interferon gamma (IFNG) is produced in mammalian cell lines a heterogenous population of IFNG polypeptides is obtained due to C-terminal processing of the IFNG polypeptide. Clearly, this constitutes a severe problem in that valuable polypeptide material is lost and, further, it is necessary to carry out time-consuming and cumbersome purification in order to obtain a homogenous population of active IFNG polypeptides having the desired length. It has now been found that an IFNG fragment containing 132 amino acid residues (truncated at the nucleotide level by introducing a stop-codon after the codon encoding amino acid residue no. 132) does not undergo C-terminal truncation or, at least, is not significantly C-terminally truncated. Furthermore, as the IFNG fragment containing 132 amino acid residues is active, this opens up the possibility of producing a homogenous active IFNG polypeptide in eukaryotic host cells, such as CHO cells.

Abstract: Human cytokine mixtures produced by cytokine regulatory factor-overexpressing cells and methods of production are disclosed. The mixtures are prepared by culturing human cytokine-producing cells under conditions of cytokine regulatory factor overexpression, treating the cells to induce cytokine production, and isolating the mixtures of cytokines produced by the cells. Preferred compositions, for use in treating viral infection or cancer, include a mixture of human interferon &ggr; and either human interferon &agr; or human interferon &bgr;, in a mole ratio of between 2:1 to 1:100 interferon &ggr; to interferon &agr; or human interferon &bgr;.

Abstract: Subjects at risk for developing cancer may be identified by obtaining samples of diagnostic cells from the subjects and determining a measure of cytotoxicity of the cells, the measure of cytotoxicity correlating negatively with the risk of developing cancer. The development of cancer may be prevented in subjects determined to be at risk for developing cancer by administering priming and activating agents to the subject, by increasing the expression of A1 adenosine receptors in cells of the subject, and increasing the affinity of cells of the subject for A1 adenosine receptor ligands. The preventative and diagnostic methods of the present invention may be carried out with kits and pharmaceutical liposomal formulations.

Abstract: Vaccine formulations for FIV related disease comprising a FIPV polynucleotide comprising a dysfunctional pol gene, FIPV polynucleotide fragments, and uses therefor in the prophylaxis and/or treatment of FIV-related diseases.

Abstract: The invention relates to macrophages which have at least one of the following properties: their cytotoxic activity without IFN-&ggr; is increased by about 20 to 30% with respect to standard macrophages, and is preferably of about 70%; their cytotoxic activity with IFN-&ggr; is increased by about 20 to 40% with respect to standard macrophages, and is preferably of about 93%; the extension of the deactivation of the cytotoxic activity in reply to an activation of IFN-&ggr; is in a ratio such that after 60 h of activation with IFN-&ggr;, the cytotoxic activity is higher than or equal to 30%, preferably of about 55%, compared to the maximum cytotoxic activity presented by the macrophages due to IFN-&ggr; activation, with said cytotoxic activity being measured as the percentage of inhibition of 3-H thymidine incorporation by target tumoral cells, particularly U 937 cells.

Abstract: Interferon composition for oromucosal contact to stimulate host defense mechanisms or an immune response in a mammal with a stimulating amount of the interferon which exceeds parenterally administered amounts of interferon, methods of treatment with such compositions and uses of interferon in the preparation of such oromucosal compositions.

Abstract: Novel antiviral combinations for the treatment or prevention of viral infections, in particular, HIV, are disclosed. This new antiviral therapy employs either DP-178 or DP-107, viral fusion inhibitors, in combination with at least one other antiviral therapeutic agent. The combinations of the invention are better than single therapies alone, and in certain cases are synergistic. The use of DP-178 or DP-107 is an ideal therapy to combine with another antiviral, given both the novel mechanism which this therapeutic blocks HIV transmission and the non-toxicity of the therapeutic.

Abstract: The present invention provides compositions comprising recombinant avian IFN-&ggr; polypeptides and methods using said recombinant avian IFN-&ggr; polypeptides and compositions to enhance the immune responses of birds, and to enhance growth and/or prevent weight loss in birds. The present invention is particularly useful in the prophylactic and therapeutic treatment of birds against coccidiosis and the causative agent thereof.

Abstract: Provided herein are methods and compositions relating to the attachment of water soluble polymers to proteins. Provided are novel methods for N-terminally modifying proteins or analogs thereof, and resultant compositions, including novel chemically modified G-CSF compositions and related methods of preparation.

Abstract: The invention concerns a method for the prevention or treatment of inflammatory bowel disease by administering an interferon-&ggr; inhibitor. The invention further concerns pharmaceutical compositions and bispecific molecules useful in such method.

Abstract: In one embodiment, a therapeutic composition containing a pentavalent antimonial is provided. The pentavalent antimonial can be sodium stibogluconate, levamisole, ketoconazole, and pentamidine and biological equivalents of said compounds. Additionally, pentavalent antimonials that can be used in accordance with the present invention may be any such compounds which are anti-leishmaniasis agents. The therapeutic composition of this embodiment contains an effective amount of pentavalent antimonial that can be used in treating infectious diseases. The types of diseases that can be treated with the present invention include, but are not limited to, the following: diseases associated with PTPase activity, immune deficiency, cancer, infections (such as viral infections), hepatitis B, and hepatitis C. The types of cancers that the present embodiment can be used to treat include those such as lymphoma, multiple myeloma, leukemia, melanoma, prostate cancer, breast cancer, renal cancer, bladder cancer.

Abstract: This invention provides method for sustained release delivery of structurally delicate agents such as proteins and peptides. Using a unique emulsion system (Stable polymer aqueous-aqueous emulsion), proteins and peptides can be microencapsulated in polysacchride glassy particles under a condition free of any chemical or physical hazard such as organic solvents, strong interfacial tension, strong shears, elevated temperature, large amount of surfactants, and cross-linking agents. Proteins loaded in these glassy particles showed strong resistance to organic solvents, prolonged activity in hydrated state, and an excellent sustained release profile with minimal burst and incomplete release when being further loaded in degradable polymer microspheres. This invention provides a simple yet effective approach to address all the technical challenges raised in sustained release delivery of proteins.

Abstract: A method of treating an inflammation in a subject in need thereof is disclosed. The method comprises locally or systemically administering to the subject IFN-&ggr; in an amount so as to achieve an IFN-&ggr; bulk tissue concentration at a site of inflammation of 1-8,000 units per kilogram body weight, thereby ameliorating the inflammation.

Abstract: The present invention relates to compositions and methods for the treatment of tumor and/or malignant and/or cancerous cells. The present invention provides VSV vectors comprising nucleic acid encoding a cytokine, such as interleukin or interferon, or a suicide gene, such as thymidine kinase, or other biological protein, such as heat shock protein gp96, or endostatin or angiostatin, wherein said VSV vectors exhibit greater oncolytic activity against the tumor and/or malignant and/or cancerous cell than a wild-type VSV vector. The present invention also provides methods of making such vectors, host cells, expression systems, and compositions comprising such VSV vectors, and viral particles comprising such VSV vectors. The present invention also provides methods for producing oncolytic activity in a tumor and/or malignant and/or cancerous cell comprising contacting said cell with a VSV vector of the present invention.

Abstract: The present invention relates to a method for facilitating activation of T-cells in a patient, comprising: identifying a patient in need of enhanced T-cell activity, administering an effective amount of a T-cell activating composition to the patient, and administering an effective amount of a compound that inhibits the production or release of intercellular reactive oxygen metabolites (ROM) to the patient. The present invention further relates to the use of H2-receptor agonists to augment the effectiveness of vaccines.

Abstract: The objects of the present invention are to reveal a specific combination of human interferon-&agr; subtypes that remarkably enhances the expression of protein synthesis inhibitory genes, and to provide an expression enhancer comprising as effective ingredients interferon-&agr; subtypes in such a combination and uses thereof. The above objects are solved by providing an expression enhancer for protein synthesis inhibitory genes which comprises as effective ingredients interferon-&agr;2 and interferon-&agr;8 subtypes of human interferon-&agr;, and uses thereof including pharmaceuticals.

Abstract: This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer. The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation stabilized-interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.

Abstract: The invention provides a composition containing two or more ADCC targeting molecules, each selective for different antigens on the surface of a target cell, and in a pharmaceutically acceptable medium. The composition can contain more than two binding species. The composition also can be a pentameric binding molecule. Also provided is a composition containing effector cells and two or more ADCC targeting molecule species in a pharmaceutically acceptable medium. The invention further provides a method of inducing antibody-dependent cell cytotoxicity (ADCC) against a target cell. The method consists of contacting the target cell in the presence of effector cells with two or more ADCC targeting molecule species each selective for different antigens on the surface of the target cell. A method of treating a pathological condition characterized by aberrant cell growth is also provided.

Abstract: The present invention provides compositions and methods for altering mitochondrial ATP metabolism, including compositions having fusion proteins comprising IF1 polypeptide-derived sequences, as well as binding and functional assays exploiting IF1 interactions with ATP synthase. Also disclosed are methods for identifying an agent capable of reducing mitochondrial ATP hydrolysis and/or increasing mitochondrial ATP synthesis, including pharmaceutical compositions identified by such methods. The invention also provides methods for treating diabetes, and in particular, type 2 DM, using an agent identified according to the disclosed methods.

Abstract: A method of making nanoparticles of interferon gamma for use in pharmaceutical formulations, and the treatment of various ailments by inhalation of these formulations are described. The interferon gamma is made into nanoparticle size using supercritical fluids technology.

Abstract: The present invention relates to a process for ameliorating or preventing neurological diseases that are caused, in part, by an increased and/or abnormal responsivity to interferon. Specifically, the invention provides a method for treating subjects suffering from or at risk for such diseases by the administration of a pharmacological preparation that antagonizes interferons' action.

Abstract: Disclosed is a DNA sequence encoding fusion protein comprising human IFN-beta and human TM-alpha1. Such fusion proteins have the valuable biological activity of both constituents and the characteristics of being unique to viral, neoplastic, multiple sclerosis and immunodeficiency diseases. These proteins are thus useful for therapeutic purposes.

Abstract: The present invention provides an ameliorant for enhancing the therapeutic effect of IFN-&agr; on hepatitis C; a therapeutic composition for the treatment of hepatitis C which comprises IFN-&agr; and IFN-&ggr; as active ingredients and further contains a pharmaceutically acceptable carrier; a kit for the treatment of hepatitis C which comprises an IFN-60 preparation and an IFN-&ggr; preparation; and a therapeutic method for the treatment of hepatitis C which comprises administering IFN-&agr; and IFN-&ggr; to a subject at the same time or administering IFN-&ggr; before the administration of IFN-&agr;. The present invention is capable of making the patient continuously HCV-RNA negative and is extremely useful in the treatment of chronic hepatitis C which is intractable with IFN-&agr; and conventionally difficult to remedy.

Abstract: Methods for the treatment of interferon-response disorders by administration of an interferon alone or in combination with adjunctive therapy are described. The invention encompasses providing to a patient both a formulation of an interferon that is suitable for short-term administration and a formulation of an interferon associated with a sustained release delivery system that is suitable for long-term administration. A principal advantage of the method is that responsiveness to treatment can be ascertained with short-term dosimetric techniques using one formulation of an interferon, which permits the appropriate selection of a dose that is both effective and safe for long-term administration using the second formulation.

Abstract: Antigen-expressing, activated dendritic cells are disclosed. Such dendritic cells are used to present tumor, viral or bacterial antigens to T cells, and can be useful in vaccination protocols. Other cytokines can be used in separate, sequential or simultaneous combination with the activated, antigen-pulsed dendritic cells. Also disclosed are methods for stimulating an immune response using the antigen-expressing, activated dendritic cells.

Abstract: The present invention relates to novel, stable recombinant gamma interferons exhibiting in greater or less degree the antiviral and antiproliferative activity in humans and pH 2 labile properties characteristic of native human gamma interferon. The amino acid sequence of such an interferon comprises, from the N-terminus: X-Y-Asp . . . Thr   1   2       126 wherein X is a methionine residue or hydrogen and Y is a glutamine residue, or, where X is hydrogen, Y is either a glutamine or a pyroglutamate residue.

Abstract: The invention relates to a novel complex for oral delivery of drugs, therapeutic protein/peptides and vaccines which are loaded in a Vitamin B2 (VB12) coupled particulate carrier system with spacers in between, the carrier system with spacers having a formula VB12-R′/R″-N wherein, R′ or R″ is spacer and/or agents for derivatization of VB12 to provide either NH2 or COOH or SH groups, and N is the micro or nano particle carriers for the delivery of injectable drugs, therapeutic protein/peptides and vaccines.

Abstract: The present invention relates to novel interferon gamma polypeptide variants having interferon gamma (IFNG) activity, methods for their preparation, pharmaceutical compositions comprising the polypeptide variants and their use in the treatment of diseases, in particular for the treatment of interstitial pulmonary diseases, such as idiopathic pulmonary fibrosis.

Abstract: The present invention is directed to compositions and methods involving the combined use of an angiogenesis inhibitor and an inducer of endogenous E-selectin. Improved methods for treating patients by inhibiting blood vessel growth are described.

Abstract: The present invention relates to a novel KDI protein which is a member of the interferon family. In particular, isolated nucleic acid molecules are provided encoding a human interferon polypeptide, called “KDI”. KDI 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 KDI activity. Also provided are therapeutic methods for treating immune system-related disorders.

Abstract: The invention concerns a novel human interferon-&egr;, originally designated PRO655, and its variants and derivatives. The novel interferon is related to but distinct from members of the IFN-&agr; family and from IFNs-&bgr; and -&ggr;. Nucleic acid encoding the novel polypeptide, and methods and means for their recombinant production are also included.

Abstract: The present invention relates to a method of increasing the sensitivity of neoplastic cells to chemotherapeutic agents by using a virus, a method of treating proliferative disorders with a virus and chemotherapeutic agents, and a method for preventing a neoplasm from developing drug resistance to chemotherapeutic agents. The virus is preferably a reovirus.

Abstract: According to a first embodiment, there is provided a sustained-release preparation comprising a water-insoluble or slightly water-soluble polyvalent metal salt of a water-soluble physiologically active substance which is not an endothelin antagonist, and a biodegradable polymer. The sustained-release preparation of the first embodiment is highly efficient in incorporating the water-soluble physiologically active substance and suppresses the initial burst of the water-soluble physiologically active substance. The sustained-release preparation of the present invention is capable of releasing the water-soluble physiologically active substance while retaining its bioactivity after administration in vivo. Furthermore, the water-soluble physiologically active substance in the sustained-release preparation is kept stable for a long period of time, with little loss of bioactivity.

Abstract: Methods for modulating the hypocretin system, as well as methods for identifying compounds that act as hypocretin-system modulators are provided. In modulating the hypocretin system, the method comprises administering a therapeutically effective amount of a preprohypocretin-expression modulator to an individual, wherein the preprohypocretin-expression modulator alters preprohypocretin expression in preprohypocretin-expressing cells. The method for identifying compounds comprises contacting a test compound to cells equipped with the 5′ flanking promoter of the preprohypocretin gene operably linked to a nucleic acid sequence and determining whether the test compound alters transcription of the nucleic acid sequence in the cell, wherein the test compound's ability to alter transcription is indicative of a compound that modulates the hypocretin system.

Abstract: The present invention relates to methods of causing MHC-class II or CD40 mediated immunomodulation, immunosuppression and anti-inflammatory action, in a subject suffering from or susceptible of suffering from a condition involving inappropriate immune response, which comprises administering to the subject at least one statin, or a functionally or structurally equivalent molecule, in an amount effective to modulate MHC class II or CD40 expression in the subject.