Abstract: A vaccine composition is provided which comprises inverted microsomes or fragments thereof from an animal cell in association with an externally disposed peptide antigen and a protein of the MHC.

Abstract: Disclosed are compositions comprising embryonic stem cells. In some embodiments, the compositions include a plurality of pluripotent cells and one or more pharmaceutically acceptable carriers or excipients. Also disclosed are methods for pro-phylaxis and/or treatment of subjects using the disclosed compositions, and methods for identifying an antigen shared by a pluripotent cell and a neoplastic or pre-neoplastic cell.

Abstract: This invention provides a method for preventing or treating Severe Acute Respiratory Syndrome in a subject comprising administering to the subject an effective amount of recombinant super-compound interferon or a functional equivalent thereof. This invention provides a method for inhibiting the causative agent of Severe Acute Respiratory Syndrome comprising contacting the agent with an effective amount of super-compound interferon or its equivalent.

Abstract: The present invention provides improved methods of imaging, targeted therapy and detection and diagnostics using modified glycoprotein hormones having increased activity over wild-type hormones.

Abstract: The invention provides an eye-drop vaccine for therapeutic immunization of a mammal comprising Copolymer 1, a Copolymer 1-related peptide, or a Copolymer 1-related polypeptide, for treating neuronal degeneration caused by an injury or disease, disorder or condition in the central nervous system (CNS) or peripheral nervous system (PNS), for preventing or inhibiting neuronal secondary degeneration which may otherwise follow primary injury in the CNS, for promoting nerve regeneration in the CNS or in the PNS after an injury, disease, disorder or condition or for protecting CNS and PNS cells from glutamate toxicity.

Abstract: The invention relates to an inhibitor of endogenous human interferon-gamma (hIFN-ϝ) in autoimmune diseases, especially in multiple sclerosis. More precisely, the invention relates to inactivated protein derivatives of the hIFN-ϝ with preserved affinity to the hIFN-ϝ receptor. The derivatives represent genetically modified variants of hIFN-ϝ where the C-terminal part of the molecule is either deleted or replaced with a polypeptide sequence of another human protein and a recombinant hIFN-ϝ inactivated by physical or chemical methods.

Abstract: The invention provides a method for the improved processing efficiency of T cell tumor antigen epitopes using bioinformatic means. The proteolytic sites in the generation of 47 experimentally identified HLA-A2.1-restricted immunodominant tumor antigen epitopes was compared to those of 52 documented HLA-A2.1-restricted immunodominant viral antigen epitopes. The amino acid frequencies in the C-terminal cleavage sites of the tumor antigen epitopes, as well as several positions within the 10 amino acid (aa) flanking regions, were significantly different from those of the viral antigen epitopes. These two groups of epitopes may be cleaved by distinct sets of proteasomes and peptidases or similar enzymes with lower efficiencies for tumor epitopes, targeted activation of the immunoproteasomes and peptidases can be achieved that mediate the cleavage of viral epitopes in order to more effectively generate tumor antigen epitopes thus enhancing antigen-specific tumor immunotherapy.

Abstract: High pressure to treat aggregated interferons, particularly recombinant human interferon-?, to reduce the aggregate content of interferon material. Highly pure, soluble monomeric recombinant interferon-? is prepared in representative embodiments. Multiple strategies may be used in combination that make nonglycosylated IFN-? more amenable to high pressure treatment. It has been found that refolding yields of high pressure treatment can be significantly improved by use of a combination of strategies, including, or example a pre-treatment of the IFN-? that involves solubilizing and then precipitating the protein. This pre-treatment is particularly effective with respect to recombinant IFN-? inclusion bodies recovered from host cells such as E. coli cells. According to another strategy, refolding under high pressure is much more effective when the refolding reagent incorporating the IFN-? incorporates a zwitterionic surfactant and/or a cholate salt.

Abstract: The present invention relates to detection, immobilization, and production of proteolytic antibodies using halogen phosphonate monoester probes, immobilizing reagents, and antigen conjugates.

Abstract: Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula I, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

Abstract: The present invention provides a novel liquid composition suitable for in-situ formation of a depot system to deliver a protein or peptide in a controlled manner. The composition of the present invention comprises: (a) a hydrophobic non-polymeric carrier material; (b) a water miscible biocompatible organic solvent that dissolves the hydrophobic non-polymeric material; (c) a protein or peptide covalently conjugated with one or more formulation performance-enhancing compounds. The present invention also provides a method of manufacturing and use of the composition thereof.

Abstract: The present invention provides methods of treating hepatitis virus infection. The methods generally involve administering a composition comprising an antiviral agent in a dosing regimen that achieves a multiphasic serum concentration profile of the antiviral agent. The dosing regimen includes dosing events that are less frequent than with currently available hepatitis therapies. The multiphasic antiviral agent serum concentration profile that is achieved using the methods of the invention effects an initial rapid drop in viral titer, followed by a further decrease in viral titer over time, to achieve a sustained viral response.

Abstract: A method of immunotherapy to treat cancer or a synergistic anti-cancer treatment by administering an effective amount of a natural cytokine mixture (NCM), an effective amount of cyclophosphamide (CY), or an effective amount of indomethacin (INDO), wherein the NCM, CY, or INDO are administered singly or in communications thereof. An anti-metastatic treatment method by promoting differentiation and maturation of immature dendritic cells in a lymph node; allowing presentation thereof; and preventing development of metastasis. A method of using an NCM as a diagnostic skin test for predicting treatment outcome. A method of pre-treating dendritic cells (DC) and a method of treating monocyte defects characterized by sinus histiocytosis or a negative NCM skin test. Compositions and methods for eliciting an immune response to endogenous or exogenous tumor antigens.

Abstract: The present invention relates generally to the fields of proteins, diagnostics, therapeutics and nutrition. More particularly, the present invention provides an isolated protein molecule that comprises a dimeric 4-helix bundle, such as IFN-a2B, IFN-b1, IFN-g, IL-10 or its receptor, such as IFNAR2, IL-10Ra or chimeric molecules thereof comprising at least a portion of the protein molecule, such as IFN-a2B-Fc, IFN-b1-Fc, IFN-g-Fc, IFNAR2-Fc, IL-IO-Fc, IL-10Ra-Fc; wherein the protein or chimeric molecule thereof has a profile of measurable physiochemical parameters, wherein the profile is indicative of, associated with or forms the basis of one or more pharmacological traits. The present invention further contemplates the use of the isolated protein or chimeric molecule thereof in a range of diagnostic, prophylactic, therapeutic, nutritional and/or research applications.

Abstract: A method for protecting a peptide from peptidase activity in vivo, the peptide being composed of between 2 and 50 amino acids and having a C-terminus and an N-terminus and a C-terminus amino acid and an N-terminus amino acid is described. In the first step of the method, the peptide is modified by attaching a reactive group to the C-terminus amino acid, to the N-terminus amino acid, or to an amino acid located between the N-terminus and the C-terminus, such that the modified peptide is capable of forming a covalent bond in vivo with a reactive functionality on a blood component. In the next step, a covalent bond is formed between the reactive group and a reactive functionality on a blood component to form a peptide-blood component conjugate, thereby protecting said peptide from peptidase activity. The final step of the method involves the analyzing of the stability of the peptide-blood component conjugate to assess the protection of the peptide from peptidase activity.

Abstract: Described herein are novel enzyme inhibitors. In some embodiments, the enzyme inhibitors are reverse transcriptase inhibitors, particularly HIV reverse transcriptase inhibitors. Also described herein are compositions containing them and methods of using them. Thus, the compounds and compositions described herein are useful for the in vitro and in vivo inhibition of HIV reverse transcriptase as a method of treating or preventing HIV, AIDS or related disorders.

Abstract: Methods, compositions and articles of manufacture for contributing to the treatment of cancers, including solid tumors, are disclosed. The methods, compositions and articles of manufacture can utilize an endothelin B agonist (ETB) to enhance the delivery and resulting efficacy of a chemotherapeutic agent.

Abstract: This invention is directed to the targeting of proteins or peptides of interest to an autophagosome, for their presentation on a major histocompatibility complex (MHC) class II molecule and methods of use thereof. Nucleic acids, vectors comprising the same, and compositions for targeting proteins or peptides of interest to an autophagosome, for their presentation on a major histocompatibility complex (MHC) class II molecule are disclosed as are methods of use thereof for stimulating or enhancing immune responses in a subject.

Abstract: The embodiments provide compounds of the general Formula I, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

Abstract: The present invention relates in general to methods and products for initiating an immune response against an antigen, and in particular relates to transepithelial delivery of antigens to provoke tolerance and immunity. The present invention further relates to methods and products for the transepithelial delivery of therapeutics. In particular, the invention relates to methods and compositions for the delivery of therapeutics conjugated to a FcRn binding partner to intestinal epithelium, mucosal epithelium and epithelium of the lung. The present invention further relates to the synthesis, preparation and use of the FcRn binding partner conjugates as, or in, pharmaceutical compositions for oral systemic delivery of drugs and vaccines.

Abstract: The present invention relates, in part, to methods and compositions for needleless delivery of macromolecules to a subject. In one aspect, the methods and compositions involve administering to the subject a delivery construct comprising a carrier construct non-covalently bound to a binding partner, wherein the carrier construct comprises a receptor-binding domain, a transcytosis domain, and a macromolecule to which the binding partner non-covalently binds, wherein the binding partner binds to the macromolecule with a Ka that is at least about 104 M?1.

Abstract: The embodiments provide compounds of the general Formulae (I) through general Formula (VIII), as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

Abstract: The invention relates to compositions and methods related to Toll-like receptor (TLR) polypeptides. In some embodiments, the invention relates to managing TLR3 related diseases. In further embodiments, the invention relates to methods of preventing and treating inflammation. In some embodiments, the invention relates to antagonists of TLR3, to amino acid sequences that act as dominant negative molecules, and to nucleic acid sequences that encode said amino acid sequences. In additional embodiments, the invention relates to the manipulation of biological materials to evaluate TLR3 activity.

Abstract: The present invention relates to a novel pharmaceutical composition of compounds having the biological activity of interferon gamma (IFN-?) or pirfenidone in combination with a diagnostic array of candidate polynucleotides for the improved treatment of all forms of interstitial lung disease, in particular of idiopathic pulmonary fibrosis (IPF).

Abstract: The present invention provides compositions and methods for the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases, for stimulating an immune response in a subject, and for use as an alternative to interleukin-12 (IL-12) treatment. In particular, the present invention provides Apicomplexa-related proteins (ARPs) that have immune stimulatory activity and thus have uses in the treatment and prevention of cancer and infectious diseases and in immune modulation. Compositions comprising an ARP are provided. Methods of use of an ARP for the prevention and/or treatment of cancer and/or infectious diseases, for use as an alternative to interleukin-12 (IL-12) treatment, and for eliciting an immune response in a subject, are also provided.

Abstract: The present invention relates to tetracyclic indole derivatives of formula (I); wherein Ar, D1, D2, D3, D4, W, X, Y and Z are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them, and their use for the treatment or prevention of infection by hepatitis C virus.

Abstract: The present invention provides a population of connective tissue derived cells that respond to interferon-gamma (IFN-?) by expressing indolamine-2,3-dioxygenase (IDO) for use in preventing, treating or ameliorating one or more symptoms associated with disorders in which modulation of a subject's immune system is beneficial, including, but not limited to, autoimmune diseases, inflammatory disorders, and immunologically mediated diseases including rejection of transplanted organs and tissues.

Abstract: Method of treating autoimmune conditions are disclosed comprising administering to a mammalian subject IL-12 or an IL-12 antagonist. In certain preferred embodiments the autoimmune condition is one which is promoted by an increase in levels of IFN-? or TNF-?. Suitable conditions for treatment include multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes melitis and autoimmune inflammatory eye disease.

Abstract: The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

Abstract: A method of treating idiophathic pulmonary fibrosis (IPF), comprising administering aerosolized interferon-? in a therapeutically effective amount to achieve improved or ameliorated symptoms of IPF.

Abstract: This invention relates to compositions and methods useful for activating LT-? receptor signaling, which in turn elicits potent anti-proliferative effects on tumor cells. More particularly, this invention relates to lymphotoxin heteromeric complexes formed between lymphotoxin-a and multiple subunits of lymphotoxin-?, which induce cytotoxic effects on tumor cells in the presence of lymphotoxin-? receptor activating agents. Also within the scope of this invention are antibodies directed against the lymphotoxin-? receptor which act as lymphotoxin-? receptor activating agents alone or in combination with other lymphotoxin-? receptor activating agents either in the presence or absence of lymphotoxin-a/? complexes. A screening method for selecting such antibodies is provided. This invention also relates to compositions and methods using cross-linked anti-lymphotoxin-? receptor antibodies either alone or in the presence of other lymphotoxin-? receptor activating agents to potentiate tumor cell cytotoxicity.

Abstract: The present invention provides improved treatment methods by the administration of the non-physiologic D-isomer of an IDO inhibitor.

Abstract: The present invention relates to immunotherapy and more specifically concerns the use of immunostimulatory BAT monoclonal antibodies for treatment of a variety of immunodeficiency related diseases and disorders and malfunction or incompetence of the immune system.

Abstract: The present invention concerns compositions comprising and methods of identification and use of targeting peptides for placenta or adipose tissue. In certain embodiments, the targeting peptides comprise part or all of SEQ ID NO:5-11, SEQ ID NO:13-22 or SEQ ID NO:144. The peptides may be attached to various therapeutic agents for targeted delivery. Adipose-targeting peptides may be used in methods for weight control, inducing weight loss and treating lipodystrophy syndrome. Adipose-targeting may also be accomplished using other binding moieties selectively targeted to adipose receptors, such as a prohibitin receptor protein complex. Placenta-targeting peptides may be used to interfere with pregnancy, induce labor and/or for targeted delivery of therapeutic agents to placenta and/or fetus. In other embodiments, receptors identified by binding to placenta-targeting peptides may be used to screen compounds for potential teratogenicity.

Abstract: The present invention relates to the field of epidermal repair. More particularly, the invention concerns the use of a molecule able to activate a heteromeric receptor comprising OSMR? as a subunit, for the preparation of a composition for activating in vitro and/or in vivo keratinocyte migration and/or the expression of anti-microbial peptides by the keratinocytes. In particular, the invention concerns the use of OSM and/or IL-17 and/or TNF? and/or IL-31, or agonists thereof, for the preparation of cosmetic or dermatologic compositions.

Abstract: The present invention relates to tetraaza phenalen-3-one compounds which inhibit poly (ADP-ribose) polymerase (PARP) and are useful in the chemosensitization of cancer therapeutics. The induction of peripheral neuropathy is a common side-effect of many of the conventional and newer chemotherapies. The present invention further provides means to reliably prevent or cure chemotherapy-induced neuropathy. The invention also relates to the use of the disclosed PARP inhibitor compounds in enhancing the efficacy of chemotherapeutic agents such as temozolomide. The invention also relates to the use of the disclosed PARP inhibitor compounds to radiosensitize tumor cells to ionizing radiation. The invention also relates to the use of the disclosed PARP inhibitor compounds for treatment of cancers with DNA repair defects.

Abstract: The present invention relates to biologically active polypeptides linked to one or more accessory polypeptides. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: Disclosed are novel methods for combating diseases characterized by deposition of amyloid. The methods generally rely on immunization against amyloidogenic proteins (proteins contributing to formation of amyloid) such as beta amyloid (A?). Immunization is preferably effected by administration of analogues of autologous amyloidogenic polypeptides, said analogues being capable of inducing antibody production against the autologous amyloidogenic polypeptides. Especially preferred as an immunogen is autologous A? which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the majority of A?'s B-cell epitopes. Also disclosed are nucleic acid vaccination against amyloidogenic polypeptides and vaccination using live vaccines as well as methods and means useful for the vaccination.

Abstract: An isomer, enantiomer, diastereoisomer or tautomer of a compound, represented by formula I: wherein: A is O, S, NR1, or CR1, wherein R1 is defined herein; represents either a single or a double bond; R2 is selected from: H, halogen, R21, OR21, SR21, COOR21, SO2N(R22)2, N(R22)2, CON(R22)2, NR22C(O)R22 or NR22C(O)NR22 wherein R21 and each R22 is defined herein; B is NR3 or CR3, with the proviso that one of A or B is either CR1 or CR3, wherein R3 is defined herein; K is N or CR4, wherein R4 is defined herein; L is N or CR5, wherein R5 has the same definition as R4; M is N or CR7, wherein R7 has the same definition as R4; Y1 is O or S; Z is N(R6a)R6 or OR6, wherein R6a is H or alkyl or NR61R62 wherein R61 and R62 are defined herein; and R6 is H, alkyl, cycloalkyl, alkenyl, Het, alkyl-aryl, alkyl-Het; or R6 is wherein R7 and R8 and Q are as defined herein; Y2 is O or S; R9 is H, (C1-6 alkyl), (C3-7)cycloalkyl or (C1-6)alkyl-(C3-7)cycloalkyl, aryl, Het, (C1-6)alkyl-aryl or (C1-6)alkyl-Het, al

Abstract: The subject invention relates to viruses that are able to replicate and thereby kill neoplastic cells with a deficiency in the IFN-mediated antiviral response, and their use in treating neoplastic disease including cancer and large tumors. RNA and DNA viruses are useful in this regard. The invention also relates to methods for the selection, design, purification and use of such viruses for cancer therapy.

Abstract: The present invention provides methods and compositions for stimulating an immune response or modulating cell signal transduction in a host by administering to said host a composition comprising at least three biomodulatory molecules connected by at least one cross-linking agent forming a chain or matrix wherein the chain or matrix functions as an immuno-stimulatory adjuvant to activate an immune accessory cell. The composition may comprise one or more types of biomodulatory molecules selected from the group consisting of cytokines, bacterial molecules, receptor ligands, antigen binding fragments of antibodies, heat shock proteins, and integrins. The composition may further comprise one or more disease-specific antigens to stimulate an immune response. The disease-specific antigens may be selected from the group consisting of tumor-associated antigens, infectious disease-associated antigens, autoimmune-associated antigens, parasitic antigens, bacterial antigens, and viral antigens.

Abstract: The present invention provides improved treatment methods by the administration of both an inhibitor of indoleamine-2,3-dioxygenase in addition to the administration of an additional therapeutic agent.

Abstract: Provided herein are phosphadiazine polymerase inhibitor, for example, of any of Formulas IV, IV?, I?, II?, or IVa, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

Abstract: Disclosed are compositions and methods for modulating Epstein-Barr virus (EBV) infection in a patient. The compositions may include peptides or peptidomimetics that are related to gp42 and function to inhibit EBV-mediated membrane fusion.

Abstract: Erythropoietin obtained from eggs laid by transgenic avians having avian N-linked and O-linked glycosylation patterns.

Abstract: Specific cytokines may be used as agents for the treatment and/or prevention of bacterial infection, by binding to components of the bacterial cell membrane and directly killing the bacteria. This finding has a number of applications in screening methods, vaccine production and clearance of bacterial components.

Abstract: The invention relates to a method of treating tumor cells within a patient wherein immature dendritic cells developed from the patient's monocyte cells and a lymphocyte cultured medium (LCM) adjuvant are introduced into the patient directly into the patient's tumor cells. The immature dendritic cells and LCM adjuvant combine with the antigens in the tumor cells to form a cancer vaccine, thereby immediately treating the tumor cells of the patient. The invention also provides a precursor treatment step of treating the patient with radiation therapy or a chemotherapy regimen.

Abstract: A peptide which selectively inhibits ?v?3 integrin which comprises the deamidation product of a peptide comprising the NGR motif.

Abstract: The present invention provides methods of treating a coronavirus infection, and methods of reducing viral load, or reducing the time to viral clearance, or reducing morbidity or mortality in the clinical outcomes, in patients suffering from a coronavirus infection. The present invention further provides methods of reducing the risk that an individual will develop a pathological coronavirus infection, that has clinical sequelae. The present invention further provides methods of reducing the risk that an individual will develop SARS. The present invention further provides methods of treating SARS. The methods generally involve administering a therapeutically effective amount of a Type I or Type III interferon receptor agonist and/or a Type II interferon receptor agonist for the treatment of a coronavirus infection.

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 administered 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 10?3 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 5,000 500,000 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.