Abstract: A method of inducing either a TH1 polarized immune response, a TH2 polarized immune response or a combined TH1 and TH2 response to an antigen and associated vaccine formulations are disclosed. A method is provided for inducing a polarized TH1 response by parenteral administration of microparticles sized such that at least 50% of the microparticles are less than 5 ?m. The microparticles containing antigen entrapped or encapsulated by a biodegradable polymer. Additionally, a method is provided for inducing a polarized TH2 response by parenteral administration of nanoparticles sized such that at least 50% of the nanoparticles are less than 600 nm, the nanoparticles containing antigen entrapped or encapsulated by a biodegradable polymer. Vaccine formulations containing the B. pertussis antigens PTd, FHA or a combination of PTd and FHA are provided.

Abstract: Dendrimers comprising a dentritic polypeptide with one dendron having terminal cationic groups and a lipidic anchor, preferably comprising C6-24-alkyl group containing ?-amino acyl groups, preferably joined to the focal group, are used to assist transfection of cells in vitro and in vivo by DNA. The complex of dendrimer and DNA may be used in gene therapy, for instance to delivery clotting factor genes to cells.

Abstract: The invention is drawn to silane copolymers prepared from the reaction of one or more polyisocyanates with one or more lubricious polymers having at least two functional groups, which may be the same or different, that are reactive with an isocyanate functional group and with one or more organo-functional silanes having at least two functional groups, which may be the same or different, that are reactive with an isocyanate functional group and at least one functional group reactive with a silicone rubber substrate. The silane copolymers of the invention can be used as coatings that are elastic when dry, lubricious when wet, and resist wet abrasion. These copolymers are useful as coatings for polysiloxane (rubber) and other difficult to coat substrates, especially for medical devices, such as catheters. These silane copolymers can contain active agents such as antimicrobials, pharmaceuticals, herbicides, insecticides, algaecides, antifoulants, and antifogging agents.

Abstract: This invention provides a vaccine for stimulating or enhancing in a subject to which the vaccine is administered, production of an antibody which recognizes a ganglioside, comprising an amount of ganglioside or oligosaccharide portion thereof conjugated to an immunogenic protein effective to stimulate or enhance antibody production in the subject, an effective amount of adjuvant and a pharmaceutically acceptable vehicle.

Abstract: This invention provides a vaccine for stimulating or enhancing in a subject to which the vaccine is administered, production of an antibody which recognizes a ganglioside, comprising an amount of ganglioside or oligosaccharide portion thereof conjugated to an immunogenic protein effective to stimulate or enhance antibody production in the subject, an effective amount of adjuvant and a pharmaceutically acceptable vehicle.

Abstract: A composition exhibiting reverse thermal gellation properties comprises a block polymer having the structure: {[An(BCB)An]}m wherein A is a polyester unit, B is a poly(ethylene oxide) unit, C is a poly(propylene oxide) unit, E is a chain extender unit, n=0-20, and m is greater than 2. The ethylene oxide:propylene oxide ratio ranges from about 0.2:1 to about 40:1. The composition has a final viscosity at a final temperature of more than twice the initial viscosity at an initial temperature wherein the final temperature is at least 10° C. higher than the initial temperature. The composition is combined with either a cellular material for tissue engineering, a cellular material for effecting repair or healing in a patient, or a bioactive agent.

Abstract: The present invention comprises novel polyoxyethylene/polyoxypropylene block copolymer compositions and compounds. The compositions comprise block copolymers that are high molecular weight molecules, and are useful in gene therapy methods.

Abstract: A vaccine for protecting a horse against diseases associated with EHV-1 and/or EHV-4 is provided. The vaccine commonly includes inactivated EHV-1 (e.g., chemically inactivated EHV-1 KyA virus) and an adjuvant. The adjuvant can include a cross-linked olefinically unsaturated carboxylic acid polymer which may have bioadhesive properties. The vaccine may also include antigens against other equine pathogens such as inactivated EHV-4 and inactivated A1 and/or A2 strains of equine influenza virus. Methods for protecting horses against diseases associated with EHV-1 and/or EHV-4 and methods of producing the equine herpesvirus vaccine are also provided.

Abstract: The present invention provides novel processes for regulating immune responses in mammalian subjects, e.g., humans, afflicted with diseases such as cancers, infections, e.g., viral infections, bacterial infections, or immune dysfunctions, especially auto-immune disorders, e.g., diabetes, Crohn's disease, rheumatoid arthritis, arteriosclerosis and ulcerative colitis. More particularly, this invention relates to generating elevated levels of an intermediary metabolite, e.g., lipids or conjugated biomolecules, e.g., glycolipids, lipoproteins and glycoproteins other than antibodies, cytokines or hormones. Treatment can be carried by introduction of the intermediary metabolite into the afflicted subject or by a reagent that when administered leads to elevated levels. The treatment regimen can be in vivo or ex vivo.

Abstract: The invention concerns a pharmaceutical preparation which improves penetration of active substances through the tissue membrane or barrier of the target organ.

Abstract: The present invention provides dihydropyrazolopyridine compounds represented by the formula (I): 1

Abstract: Compositions comprising non-ionic block copolymers are useful for the treatment of autoimmune, inflammatory and proliferative diseases and for reducing graft/implantation rejection. The present invention also relates to methods of treating animals having various autoimmune, inflammatory and proliferative diseases. The present invention also relates to methods of reducing inflammation in an animal comprising administering the compositions of the invention. Also, the present invention relates to methods of reducing autoimmune responses and to methods of reducing graft/implantation rejection comprising administering the compositions of the inventions. A typical embodiment is a mixture of Pluronics F127 and L61.

Abstract: A kit useful for immunization is described. The kit contains an antigenic substance from a Mycobacterium and an adjuvant combination of dimethyl dioctadecyl ammonium bromide and monophosphoryl lipid A.

Abstract: Mucosal adjuvants for vaccines contain water-soluble polyanionic polymers which have anionic constitutional units obtained from acids such as acrylic acid, methacrylic acid, maleic acid, fumaric acid, ethylsulphonic acid, vinylsulphuric acid, vinylsulphonic acid, styrenesulphonic acid, vinylphenylsulphuric acid, 2-methacryloyloxyethane sulphonic acid, 3-methacryloyloxy-2-hydroxypropanesulphonic acid, 3-methacryl amido-3-methylbutanoic acid, acrylamidomethylpropanesulphonic acid, vinylphosphoric acid, 4-vinylbenzoic acid, 3-vinyl oxypropane-1-sulphonic acid, N-vinylsuccinimidic acid, and salts of the foregoing. The polyanionic polymers may further have hydrophobic constitutional repeating units, such as alkylesters, cycloalkylesters, hydroxyalkylesters, ethers, glycols, aromatic groups and salts thereof. The adjuvants containing the polyanionic polymers are used in vaccines for the induction or enhancement of mucosal immune responses.

Abstract: An immunological response potentiation process is disclosed for synthetic or genetically engineered antigens having low immunogenicity. The antigen is embedded into biodegradable microparticles, and the antigen-loaded microparticles are dispersed in a biodegradable medium. When parenterally administered, the antigen-loaded microparticles trigger a potentiated antibody, TH-lymphocyte and Tc-lymphocyte response, as compared to an aqueous antigen solution. The extent of immunological potentiation is at least comparable with that attained by Incomplete Freund's adjuvant compositions. Linear B-TH-cell epitopes, linear Tc-cell epitopes, dimers and multimers of those epitopes, and mixtures thereof, are used as low immunogenicity antigens. The microparticles are based on biodegradable biopolymers such as polyester, polyanhydride, and polyorthoester.

Abstract: The invention is drawn to silane copolymers prepared from the reaction of one or more polyisocyanates with one or more lubricious polymers having at least two functional groups, which may be the same or different, that are reactive with an isocyanate functional group and with one or more organo-functional silanes having at least two functional groups, which may be the same or different, that are reactive with an isocyanate functional group and at least one functional group reactive with a silicone rubber substrate. The silane copolymers of the invention can be used as coatings that are elastic when dry, lubricious when wet, and resist wet abrasion. These copolymers are useful as coatings for polysiloxane (rubber) and other difficult to coat substrates, especially for medical devices, such as catheters. These silane copolymers can contain active agents such as antimicrobials, pharmaceuticals, herbicides, insecticides, algaecides, antifoulants, and antifogging agents.

Abstract: The present invention relates to a chemically modified polypeptide in which at least one of hydroxyl groups in the polypeptide molecule is modified with a polyalkylene glycol derivative; a method for producing the modified polypeptide; a method of treatment using the modified polypeptide; use of the modified polypeptide; a pharmaceutical preparation comprising the modified polypeptide; and a composition for treatment comprising the modified polypeptide.

Abstract: One aspect of the present invention relates to methods and compositions for attenuating xenograft rejection by administering, to an animal receiving the xenograft, an amount of a polymer-derivatized xenoantigen (hereinafter “xenopolymer”) effective for inhibiting or lessening the severity of hyperacute rejection response (HAR), or other immunological response to the graft, that is dependent on the presence of the xenoantigen on the grafted tissues or cells. In certain embodiments, the xenopolymer is administered in an amount sufficient to neutralize host antibodies (“xenoreactive antibodies” or “XNA”) immunoreactive with the xenoantigen. The xenopolymer may additionally, or alternatively, be used as a tolerogen (or anergen) for the xenoantigen, e.g., able to suppress, to some degree, the production/secretion of XNAs by the immune system of the host.

Abstract: Art adjuvant composition for stimulating an effective immune resposne to an antigenic substance when co-administered to an animal with said antigenic substance, comprising: (a) a saponin with immune stimulating activity; (b) a polycationic polyelectrolyte with immune stimulating activity; and (c) an immunoadjuvant oil.

Abstract: A method and structure for forming a viral-physiological structure. A naked virus having a capsid is provided. A linker molecule having a covalently attached polymer is covalently bonded to the capsid to form a polymer-protected virus. An immunogenicity of the polymer-protected virus with respect to an animal exceeds an immunogenicity of the naked virus with respect to the animal.

Abstract: A formulation for depositing a film on a substrate comprising 5 to79.9 wt. % of an alkylene trialkoxy terminated polysiloxane; 0.01 to 5 wt. % of a catalyst; 20 to 94.99 to wt % of a volatile diluent, and, optionally, 0.01 to 5 wt. % of an alkoxysilane and 0.1 to 25 wt % of a filler. The formulations are especially valuable for forming films to be used in personal care or healthcare applications.

Abstract: The present invention includes novel polyoxyethylene/polyoxypropylene block copolymers as well as methods for making the block copolymers. The block copolymers are high molecular weight molecules and are useful as general surfactants and display enhanced biological efficacy as vaccine adjuvants.

Abstract: The present invention relates to novel therapeutic and diagnostic arrays. More particularly, the present invention is directed to dendrimer based multifunctional compositions and systems for use in disease diagnosis and therapy (e.g., cancer diagnosis and therapy). The compositions and systems generally comprise two or more separate components for targeting, imaging, sensing, and/or triggering release of a therapeutic or diagnostic material and monitoring the response to therapy of a cell or tissue (e.g., a tumor).

Abstract: Polymers and polymer conjugates comprising crosslinked Staphylococcal protein A, or crosslinked protein A-superantigen, or crosslinked functional derivatives thereof ranging in size from 12kDa to 1O,OOOkDa are useful in the treatment of autoimmune diseases, such as rheumatoid arthritis and ITP as well as neoplastic diseases. Compositions and pharmaceutical composition comprising chemically crosslinked polymers of protein A alone or protein A and bacterial enterotoxins, optionally further complexed with immunoglobulins and complement components, are disclosed, as are methods for making and using these compositions in the treatment of diseases. Plasma perfusates of protein A immunadsorbent columns in clinical use are shown to act through the leaching of polymers of protein A and protein A-Staphylococcal enterotoxin B having a broad range of molecular masses.

Abstract: The present invention includes novel polyoxyethylene/polyoxypropylene block copolymers as well as methods for making the block copolymers. The block copolymers are high molecular weight molecules and are useful as general surfactants and display enhanced biological efficacy as vaccine adjuvants.

Abstract: The invention features a non-immunogenic construct for reducing a non-primary antibody response to an epitope of a T-dependent antigen. The construct is free of high molecular weight immunostimulatory molecules and contains copies of the epitope which bind to a B cell membrane immunoglobulin receptor specific for the epitope but fail to form an imnunon.

Abstract: Multispecific molecules which target immune cells are disclosed. The molecules are “multispecific” because they bind to multiple (two or more), distinct targets, one of which is a molecule on the surface of an immune cell. Multispecific molecules of the invention include molecules comprised of at least one portion which binds to a molecule on an effector cell, such as an Fc receptor, and at least one portion (e.g., two, three, four or more portions) which binds to a different target, such as an antigen on a tumor cell or a pathogen. Multispecific molecules of the invention also include antigen “multimer complexes” comprised of multiple (i.e., two or more) portions which bind to a molecule on an antigen presenting cell (APC), such as an Fc receptor, linked to one or more antigens. These multimer complexes target antigens, such as self-antigens, to APCs to induce and/or enhance internalization (endocytosis), processing and/or presentation of the antigen by the APC.

Abstract: Compositions are provided which include biodegradable microparticles with entrapped or adsorbed antigens, in combination with submicron oil-in-water emulsions. Also provided are methods of immunization which comprise administering to a vertebrate subject (a) a submicron oil-in-water emulsion, and (b) a therapeutically effective amount of a selected antigen entrapped in a microparticle.

Abstract: A method of making a non-immunogenic construct for reducing a non-primary antibody response to an epitope of a T-dependent antigen by coupling two or more copies of the epitope to a nonimmunogenic soluble carrier to yield a conjugate preparation and removing high molecular weight immunostimulatory molecules.

Abstract: The present invention relates to therapeutic methods and compositions employing superantigens. Methods and compositions employing superantigens and immunotherapeutic proteins in combination with one another have been found to provide more effective treatment than either component used alone. Superantigens, in conjunction with one or more additional immunotherapeutic antigens, may be used to either induce a therapeutic immune response directed against a target or to inhibit a disease causing immune response. Specific combinations of superantigens and immunotherapeutic antigens are used to treat specific diseases. The induction (or augmentation) of a desired immune against a target may be used, for example, to kill cancer cells or kill the cells or an infectious agent. The inhibition of an immune response, e.g., through the induction of T cell anergy, may be used to reduce the symptoms of an autoimmune disease.

Abstract: Vaccine adjuvants comprising a liquid medium contain polymers with anionic constitutive repeating units and hydrophobic constitutive repeating units. Advantageously, the adjuvants are aqueous solutions of partially esterified polyacrylic acids. The novel adjuvants are highly stable, effective and have a relatively low level of local toxicity. Further, vaccines comprising such adjuvants and a process for producing them are described.

Abstract: A method for producing a conjugate vaccine includes mixing a uronium salt reagent with a first moiety (e.g., a polysaccharide). According to the invention, the uronium salt reagent has a chemical structure corresponding to formula I: wherein R1 is defined as wherein R6 represents the carbon, hydrogen, and optionally one or more heteroatoms which, together with the nitrogen atom to which they are attached, constitute a 5 to 10 membered heterocyclic ring, which may be substituted or unsubstituted. R2, R3, R4, and R5, each independently represents a hydrogen atom, a substituted or unsubstituted alkyl having 1 to 6 carbon atoms, a substituted or unsubstituted alkenyl having 2 to 6 carbon atoms, or an alkynyl having 2 to 6 carbon atoms. Alternatively, R2 and R3, when taken together, can represent the carbon, hydrogen, sulfur, nitrogen, or oxygen atoms necessary to complete a 5 to 7 membered heterocyclic ring with the nitrogen atom to which they are attached.

Abstract: Method of eliciting in a mammalian host a protective immune response to Helicobacter infection and treatment of Helicobacter infection by administering to the host an immunogenically effective amount of a Helicobacter urease or urease subunits as antigen. Vaccine compositions are also provided.

Abstract: A method for determining the susceptibility of a patient to cancer comprising the steps (i) obtaining a sample containing nucleic acid derived from the patient; and (ii) contacting the said nucleic acid with a nucleic acid capable of selectively hybridising to the region of human chromosome 10 which region is bounded by DNA defined by the markers D10S541 and D10S215. A nucleic acid capable of selectively hybridising to the region of human chromosome 10 which region is bounded by DNA defined by the markers D10S541 and D10S215 provided that the nucleic acid is not any one of certain YACs, BACs, PACs or ESTs defined herein. Preferably the said nucleic acid is a prostate tumour suppressor gene.

Abstract: A therapeutic composition comprising (i) at least one antigen or at least one in vivo generator of a compound comprising an amino acid sequence and (ii) at least one adjuvant comprising at least one pharmaceutically acceptable and water-soluble salt of an organic anion and a metal cation.

Abstract: Stabilized dried pharmaceutical compositions dispersible in aqueous liquid or injection comprise (i) virus e.g. for use as a vaccine or vector, preferably a herpesvirus, e.g. attenuated or genetically disabled infectious herpes simplex virus or varicella zoster virus, (ii) polysaccharide, e.g. dextran, and/or a source of mixed aminoacids of vegetable or bacterial origin, (iii) a buffer, and (iv) a mono- or oligo-saccharide or derivative thereof.

Abstract: Methods and compositions are provided for tolerizing shed antigen-specific B cells involved in an immune complex-mediated disease progression. The composition comprises a substantially non-immunogenic carrier molecule to which is linked carbohydrate chains containing a suppressive amount of a repeated, antigenic carbohydrate determinant derived from a shed antigen of interest. In a method of tolerizing shed antigen-specific B cells involved in an immune complex-mediated disease progression, administered to an individual is a therapeutically effective amount of the composition which, when contacting the shed antigen-specific B cells, induces tolerization of the shed antigen-specific B cells.

Abstract: Novel homodimers that include cysteine-containing peptides having 4-15 amino acid residues can be administered to modulate the immune response in an animal.

Abstract: aPL analogs that (a) bind specifically to B cells to which an aPL epitope binds and are disclosed. Optimized analogs lack T cell epitope(s) are useful as conjugates for treating aPL antibody-mediated diseases. Methods of preparing and identifying said analogs, methods of treatment using said analogs, methods and compositions for preparing conjugates of said analogs and diagnostic immunoassays for aPL antibodies are disclosed.

Abstract: A soluble polyphosphazene polyelectrolyte immunoadjuvant is disclosed. In one embodiment, the polymeric adjuvant is poly[di(carboxylatrophenoxy)phosphazene] which is in the form of a microsphere and which is adsorbed with antigen after formation of the microsphere. The immunoadjuvant can be administered intranasally.