Abstract: Disclosed are chimeric proteins having a cytokine fused to an enzymatically inactive polypeptide which increases the circulating half-life of the cytokine. The chimeric proteins are useful for treating, inhibiting, or preventing a variety of conditions, including septic shock, granulomatous disorders, Type I diabetes, and various cancers (e.g., multiple myeloma) in a patient.

Abstract: The present invention relates to interferon-immunoglobulin Fc fusion proteins (referred to as “IFN-Fc hybrids”) and their use in treating tumors. The IFN-Fc hybrids preferably (but not necessarily) include linkers between the IFN and the Fc portion, and the IFN portion can be an IFN variant. These linkers are preferably composed of a T cell inert sequence, or any non-immunogenic sequence, including Gly-Ser repeat units. The preferred Fe fragment is a human immunoglobulin Fc fragment, preferably the &ggr;4 chain.

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: Oligonucleotides containing unthylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response in a subject are disclosed. Also disclosed are therapies for treating diseases associated with immune system activation that are initiated by unthylated CpG dinucleotides in a subject comprising administering to the subject oligonucleotides that do not contain unmethylated CpG sequences (i.e. methylated CpG sequences or no CpG sequence) to outcompete unmethylated CpG nucleic acids for binding. Further disclosed are methylated CpG containing dinucleotides for use antisense therapies or as in vivo hybridization probes, and inmmunoinhibitory oligonucleotides for use as antiviral therapeutics.

Abstract: The invention relates to a method of modulating neutralizing antibodies formation against an heterologous protein. The invention also relates to the use of such method to induce a tolerisation of the immune system towards said protein, such tolerisation being useful to allow long-term gene therapy or transgene expression. The invention also relates to the use of a method of the invention to provide an animal with a reproducible functional inactivation phenotype of an endogenous protein of the animal.

Abstract: The present invention deals with gene therapy for treating chronic heart failure and other cardiac disease states which are accompanied by a reduced number or functioning of myocardial beta-adrenergic receptors (&bgr;-AR). &bgr;-AR receptor function is augmented in transgenic animals by delivery and expression of a beta-2-adrenergic receptor gene or a gene encoding a beta adrenergic receptor kinase inhibitor, resulting in increased in vivo left ventricular function. The present invention includes recombinant plasmid vectors, alternative beta-adrenergic receptor gene delivery strategies, and transgenic mice carrying a &bgr;-AR transgene, a &bgr;-ARK transgene, or a &bgr;-ARK inhibitor transgene.

Abstract: The present invention is directed to bacteriophage therapy, using methods that enable the bacteriophage to delay inactivation by any and all parts of the host defense system (HDS) against foreign objects that would tend to reduce the numbers of bacteriophage and/or the efficiency of those phage at killing the host bacteria in an infection. Disclosed is a method of producing bacteriophage modified for anti-HDS purposes, one method being selection by serial passaging, and the other method being genetic engineering of a bacteriophage, so that the modified bacteriophage will remain active in the body for longer periods of time than the wild-type phage.

Abstract: Disclosed are a composition of chemically defined components having elevated levels of simple sugars which support the enhanced in vitro chondrogenesis of mesenchymal progenitor cells, a method for in vitro chondrogenic induction of such progenitor cells and a method of forming human chondrocytes in vitro from such progenitor cells.

Abstract: Described are medical devices which are or can be used to form tubular medical devices, and related methods. Preferred devices include tubular grafts of biomaterial having lumen walls which present no seam edge that traverses the entire length of the lumen, illustratively including devices having lumen walls which have a discontinuous seam presenting multiple seam edges. Such a device may include a tubular structure formed by inserting a plurality of extensions of a biomaterial sheet through a plurality of corresponding apertures of the sheet.

Abstract: Pieces of extracellular matrix (ECM), including ECM harvested from tissue donors, are used to preserve the unique characteristics of cultured cells. Using this method, cells cultured from the annulus fibrosis are more likely to retain the unique features of fibrocytes, and cells of the annulus fibrosis, if portions of annulus fibrosis ECM are included in the culture media for culturing annulus fibrosis cells. The technique is extendable to other types of cell and tissue cultures, including chondrocytes, nucleus pulposis cells, and so forth. Additional therapeutic substances may be added cell/matrix culture In addition, although the cultured cells are well suited to annulus fibrosis augmentation and/or transplantation, the invention is not limited to treatment of the intervertebral disc. For example, the invention could also be used to treat other tissues of the body such as the meniscus of the knee.

Abstract: This invention provides a method of treating cancer by administering a replication competent adenoviral vector comprising a therapeutic gene and a disease specific gene regulatory region operationally linked to at least one replication gene. The replication competent targeted adenoviral vector preferentially replicates in the tumor cells following activation of the tumor specific gene regulatory region thereby amplifying the effect of the therapeutic gene carried by the replication competent adenoviral vector. This invention enables for the first time the targeting of a therapeutic gene for treating cancer using small amounts of viral vectors which selectively replicate to deliver therapeutic dosages of the therapeutic gene.

Abstract: The present invention relates to preventive, therapeutic, and diagnostic compositions and methods employing lymphocytes having T-cell receptors and chimeric receptors. In particular, the invention relates to pre-selected dual-specificity lymphocytes having endogenous T-cell receptors and chimeric T-cell receptors that recognize a strong antigen and tumor associated antigens where the pre-selected population of adoptively transferred lymphocytes is activated by in vivo immunization, thereby increasing the effectiveness of adoptive immunotherapy.

Abstract: The present invention provides improved conditionally replicating vectors that have improved safety against the generation of replication competent vectors or virus. Also disclosed are methods of making, propagating and selectively packaging, modifying, and using such vectors. Included are improved helper constructs, host cells, for use with the improved vectors as well as pharmaceutical compositions and host cells comprising the vectors, the use of vector containing host cells to screen drugs, and methods of using the vectors to determine gene function. The methods also include the prophylactic and therapeutic treatment of disease, especially viral infection, and HIV infection in particular.

Abstract: Replication-competent adenovirus vectors specific for cells expressing carcinoembryonic antigen (CEA), and methods of use of such viruses are provided. These viruses comprise an adenoviral gene under control of a CEA transcriptional regulatory element (CEA-TRE). The gene can be, for example, a gene required for viral replication or the adenovirus death protein gene (ADP). The viruses can also comprise at least one other adenoviral gene under control of another transcriptional regulatory element specific to cells capable of which allow a CEA-TRE to function, such as a variant of a CEA-TRE. By providing for transcriptional initiating regulation dependent upon CEA expression, virus replication can be restricted to target cells which allow a CEA-TRE to function, such as cells expressing CEA, particularly carcinoma cells capable of expressing CEA. An adenovirus of the present invention can further comprise a heterologous gene such as a reporter gene under transcriptional control of a CEA-TRE.

Abstract: This invention provides HIF-3&agr; nucleic acid and sequences. Also provided are methods for using HIF-3&agr; nucleic acids, proteins, fragments, antibodies, probes, and cells, to characterize HIF-3&agr;, modulate HIF-3&agr; cellular levels, induce angiogenesis, improve muscular function, and treat coronary and cardiac diseases in mammals.

Abstract: A method of treating skin conditions by providing compositions containing enzymes to selectively remove specific layers of skin. The depth of skin removed (that is, vertical surface treated) is regulated by the type and concentration of enzyme or enzymes in the composition. The surface area of skin removed (that is, radial surface treated) is regulated by the area of topical application. Conditions treatable by the method include, but are not limited to, age-related conditions such as lines and wrinkles, infections, pigmentary disorders, follicular disorders such as acne, and hyperkeratotic disorders such as warts. The inventive method and composition thus achieves the specificity and efficacy of more invasive methods such as surgery, while providing a composition that may be topically applied and is easy to use.

Abstract: Compositions and methods for controlling insects by co-expressing an amino acid oxidase and a second enzyme that provides insecticidal activity when present in a mixture with the amino acid oxidase are disclosed. Also disclosed are DNA and protein sequences, and transformed microorganisms and plants useful for achieving such insect control.

Abstract: The present invention provides for a method for treating a subject suffering from a condition associated with an extracellular zinc sphingomyelinase activity which comprises administering to the subject an amount of a zinc sphingomyelinase inhibitor effective to decrease extracellular zinc sphingomyelinase activity in the subject and thereby treat the subject.

Abstract: The invention provides synergistic combinations of fungicides and enzymes breaking down cell walls of yeasts and filamentous fungi. The fungicides are polyene macrolides, preferably nystatin and/or natamycin. The cell wall degrading enzymes are preferably used in combinations. They include cellulases, chitinases, mannanases, proteases and the like. The use of compositions according to the invention in the field of crop protection, especially for protection of flower bulbs, is also disclosed.

Abstract: Methods of thrombolysis that allow the use of a fibrinolytic composition comprising reversibly inactivated acidified plasmin and the localized delivery of the plasmin to a vascular thrombotic occlusion are disclosed. Further disclosed is a method for administering a therapeutic dose of a fibrinolytic composition substantially free of plasminogen activator to a human or animal having a vascular thrombotic occlusion. The fibrinolytic composition includes a reversibly inactivated acidified plasmin substantially free of plasminogen activator. Intravascular catheter delivery of the fibrinolytic composition directly into or in the immediate vicinity of the thrombus is disclosed to minimize the systemic degradation of fibrin while retaining the maximum plasmin activity against the thrombus.

Abstract: Methods and compositions are disclosed that are useful for the prevention and/or treatment of cardiovascular and cardiac diseases and disorders, or damage resulting from surgical or medical procedures that may cause ischemic or ischemic/reperfusion damage in humans; and cardiovascular trauma. The beneficial effects of the compositions and methods are achieved through the use of pharmaceutical compositions that include agents that interfere with the production and/or biological activities of sphingolipids and their metabolites, particularly sphingosine (SPH) and sphingosine-1-phosphate (S-1-P). Also disclosed are methods for identifying and isolating therapeutic agents.

Abstract: The invention concerns novel DNA and amino acid sequences of monoclonal antibodies (mAbs) raised against lymphoblastoid cells and peptides to which the mAbs bind to. The invention also concerns diagnostic assays using said antibodies or peptides for detecting individuals with a high probability of having a malignant disease and, at times, for detecting an individual having a specific malignant disease. The invention further concerns pharmaceutical compositions comprising the mAbs or peptides of the invention for use in the treatment of various malignant diseases as well as methods for the treatment of malignant diseases using the mAbs or peptides of the invention.

Abstract: The invention relates to methods and products for treating cancer. In particular the invention relates to combinations of nucleic acids and antibodies for the treatment and prevention of cancer. The invention also relates to diagnostic methods for screening cancer cells.

Abstract: Methods are provided for inhibiting or suppressing viral replication in an infected host cell. More specifically, methods are provided for inhibiting or suppressing viral replication in an infected host cell by administering compounds that interfere with the binding of C-X-C chemokines to C-X-C chemokine receptors. Such methods are advantageous for treating viral infections such as human immunodefeciency virus infections.

Abstract: Use of an agent capable of inhibiting the interaction between SIRP1&agr; and CD47, in the preparation of a composition for the inhibition of macrophage involvement in autoimmune disease. The invention further relates to a method for the treatment of an autoimmune disease with macrophage involvement, comprising administering to a mammal an effective amount of an agent which inhibits the interaction between CD47 and SIRP1&agr;. The invention also relates to a method for identifying an agent capable of inhibiting the interaction between CD47 and SIRP1&agr;, comprising the steps of exposing one or more test compounds to CD47 and/or SIRP1&agr;, and monitoring the ability of the test compound to inhibit their interaction.

Abstract: New combined therapeutic regimens for treatment of B-cell lymphomas are disclosed which comprise in particular administration of anti-CD20 antibodies to patients having low-, intermediate- or high-grade non-Hodgkins lymphomas.

Abstract: There is disclosed antibody molecules containing at least one CDR derived from a mouse monoclonal antibody having specificity for human TNF&agr;. There is also disclosed a CDR grafted antibody wherein at least one of the CDRs is a hybrid CDR. Further disclosed are DNA sequences encoding the chains of the antibody molecules, vectors, transformed host cells and uses of the antibody molecules in the treatment of diseases mediated by TNF&agr;.

Abstract: The invention concerns methods of treating IL-1-mediated disease by administering a selective IL-1 binding agents that form an antagonist complex with the IL-1 ligand. The antagonist complex can bind to the IL-1 receptor without activating the receptor. The selective binding agents contemplated by this invention thus have the properties of free ligand absorption (through binding of the selective binding agent to free IL-1&agr; or &bgr;) and receptor activation inhibition (through binding of the antagonist complex to the receptor and preventing its activation).

Abstract: The invention is directed to improved immunopotentiating systems for preparation of immunogenic materials. More particularly, the invention is directed to immunogenic compositions containing a protein, polypeptide, or peptide, a hydrophobic anchor, and a proteosome. The immunogenic compositions are suitable for use as therapeutic agents and vaccines.

Abstract: A process for increasing the concentration of HDL cholesterol in the blood of a mammal whose blood contains cholesterol ester transfer protein (CETP) is contemplated. That process comprises the steps of: (a) immunizing the mammal with an inoculum containing a CETP immunogen that is an immunogenic polypeptide having a CETP amino acid residue sequence that is covalently bonded to an exogenous antigenic carrier polypeptide and is dissolved or dispersed in a vehicle; and (b) maintaining the immunized mammal for a time period sufficient for said immunogenic polypeptide to induce the production of antibodies that bind to CETP and lessen the transfer of cholesteryl esters from HDL. Immunogens, inocula and DNA segments useful for carrying out the invention are also disclosed.

Abstract: Methods and compositions for the treatment of microbial infection, and in particular meningococcal disease, comprise a commensal Neisseria or an extract of a commensal Neisseria. Further methods and compositions comprise commensal Neisseria which express genes from virulent strains of Neisseria and/or heterologous gene products from non-neisserial sources. Such compositions are used in vaccine preparations for the treatment of microbial infection.

Abstract: Novel isolated enzymes exhibiting rhamnogalacturonan hydrolase activity and belonging to a glycosyl hydrolase family other than family 28 are obtained and cloned from bacterial strains, for example, Bacillus licheniformis, Bacillus subtilis, Bacillus halodurans, Bacillus agaradhaerens, Caldicellulosiruptor, Streptomyces and Sorangium.

Abstract: The present invention discloses an anti-obesity agent comprising:

Abstract: Methods for treating obesity are disclosed which comprise administration of a therapeutically effective amount of an amylin or an amylin agonist alone or in conjunction with another obesity relief agent.

Abstract: The present invention relates to a stable compacted, compressed or hard tableted injectable composition, including a vaccine composition comprising at least one freeze dried antigenic component and a dissolution aid. A package containing the above injectable composition and method to facilitate immunizing a subject against a disease comprising the steps of first dissolving the compacted, compressed or hard tableted vaccine composition in a package with a diluent to form a vaccine solution, and administering the resulting vaccine solution in an amount effective for immunizing is also provided.

Abstract: Disclosed herein is a vaccine which provides immunity to mammals from infection and/or disease caused by a lentivirus, such as equine infectious anemia virus, human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV) or simian immunodeficiency virus (SIV) said composition comprising a deletion in a gene that blocks replication of the virus in vivo. Said composition allows differentiation between vaccinated and non-vaccinated, but exposed, mammals and provides safety and immunity when administered as a vaccine to mammals. Preferably said composition encompasses at least one deletion in a lentivirus which allows mammals to be safely vaccinated and provides protection from exposure to wild-type lentiviruses. It also encompasses a marker vaccine in which a foreign gene is inserted into the gene-deleted region, said inserted gene providing a diagnostic tool for use in vaccinated mammals and, potentially, protection from infection from a foreign disease.

Abstract: The present invention relates to cosmetic compositions having improved application benefits to keratinous tissue and keratinous fibers wherein said compositions have improved application benefits, while avoiding the negatives associated with compositions currently known in the art. The cosmetic compositions comprise a phospholipid, a PVP copolymer and a water insoluble latex and provide hair fiber thickening, separation, detangling combined with long wear. Applicants have also found that the compositions disclosed herein are also useful for other cosmetic applications that relate to keratinous tissues like skin, e.g., lipsticks, foundations, mascaras, eyeliners, lipliners, eyeshadows, rouges, etc., where it is desirable to provide a smooth application of a long wearing, film-forming cosmetic product.

Abstract: The present invention relates to cosmetic compositions having improved application benefits to keratinous tissue and keratinous fibers wherein said compositions have improved application benefits, while avoiding the negatives associated with compositions currently known in the art. The cosmetic compositions exhibit a turning point stress of from about 650 Pa to about 1500 Pa and a high shear rate slope of less than about 0.5 Pa-s. Applicants have also found that the compositions disclosed herein are also useful for other cosmetic applications that relate to keratinous tissues like skin, e.g., lipsticks, foundations, eyeliners, lipliners, eyeshadows, rouges, etc., where it is desirable to provide a smooth application of a long wearing, film-forming cosmetic product.

Abstract: Cosmetic and pharmaceutical compositions for topical application which include a liquid carrier, a magnetic metalloprotein and magnetic particles.

Abstract: The present invention relates to a composition for external application, a humectant and a skin barrier function reinforcing agent, each containing a diamide derivative represented by the following formula (1): 1

Abstract: A cream, comprising about 5 to 60% of a non-swelling clay, a swelling clay, a natural or synthetic gum, a surfactant, a hydrophilic and/or hydrophobic solvent, wherein, after application to a surface, dries to a uniform, visible, substantive, abrasion-resistant powder. The cream/powder composition is useful for a protective skin covering for preventing conditions such as bed sores, diaper rash, poison ivy or soothing uncomfortable feet, or as a delivery vehicle for a therapeutically-active dermatological agent, such as acne or fungal treatments, or as the delivery vehicle for treating other types of conditions, such a sore muscles, sore joints or microbial infections. Methods of making and using the cream also are included.

Abstract: Use of a cosmetic and/or dermatological and/or hygiene composition containing an effective quantity of at least one ion chelating agent for increasing the tolerance threshold of sensitive or intolerant skin

Abstract: The present invention refers to a solid, preferably transparent cosmetic product. In one embodiment the solid cosmetic product comprises: from 0.5% to 30% of at least one alkyl ether from polysaccharides; from 0.1% to 55% of at least one dibutyl lauroyl glutamide or derivatives; and from 1% to 95% of non-polar organic liquids.

Abstract: The present invention relates to compositions and methods for administering compositions in solutions for killing adult lice and the ova comprising water, PVM/MA Decadiene crosspolymers, propylene glycol, a mixture of cetyl and stearyl alcohols, Ceteareth-20; stearalkonium chloride; benzyl alcohol; hexylene glycol; pentylene glycol, isopropyl alcohol; a mixture of spinosyn A and spinosyn D in a weight ratio of 80:20, BHT; and sodium hydroxide.

Abstract: An insect repellent composition containing citronella oil, D-limonene, 2 or more synergists, and 3 or more essential oils as the active ingredients. The preferred essential oils are geranium oil, rosemary oil and peppermint oil, but other essential oils may be used. In the preferred embodiment the synergists are aldehyde C-14 and aldehyde C-18. As desired, vanillin may be used as a stabilizer, and fragrances, fragrance enhancers and surfactants may be utilized.

Abstract: A covering for soft furnishing is impregnated with an insecticide, such as permethrin. The concentration of permethrin is sufficient to kill house dust mites and deter larger insects such as fleas and ticks. The insecticide is released from the covering over an operational period so as to encourage the absorption of the insecticide into surrounding soft furnishings. The covering is manufactured from machined fabric, such as knitted voile, having interstices sufficiently small to reduce the rate of insecticide release over the operational period.

Abstract: A method of making a coating for deterring woodpeckers from damaging wood using Isophorone and the composition made therefrom. The Isophorone is combined with heated wax and combined with a thickener, such as a clay thickener and a silica thickener, and mixed with an acrylic resin. The composition is cooled and blending with ceramic pellets under a vacuum and dried. The dried pellets are then added to a polymer resin, such as an epoxy resin to form a coating material that will deter woodpeckers.

Abstract: A sugar-free composition comprising a mixture of at least two polyols present in an amount from about 15 to 80% by weight, an emulsifier system present in an amount from about 1.0 to 30% by weight, an active agent in an amount from about 0.1 to 70% by weight and water in an amount from 0 to 15% by weight with optional components comprising colors, flavors and binders totalling 100%. Also, a method of preparing a sugar-free composition comprising the steps of mixing from about 15 to 80% by weight of at least two polyols with about 0 to 15% by weight water, heating the mixture to about 200-260° F. for about 5 to 10 minutes, cooling the mixture to about 175-240° F., adding to the mixture about 1.0 to 30% by weight an emulsifier system to form a further mixture, cooling the further mixture to about 100-110° F., and adding to the cooled further mixture about 0.1 to 70% by weight of an active ingredient to form the sugar-free composition.

Abstract: The present invention includes additives that are used for making novelty edible comestibles and/or scented products. The additives are specifically geared towards men and women, so as to provide for a final product that is exciting to utilize and one that will produce favorable results. The additives added have medically been proven to significantly increase penile blood flow in men and increase vaginal blood flow. This increase in blood flow in both men and women is an indication of sexual arousal.