Abstract: Soluble amphiphilic macrocycle analogues having lipophilic groups attached to one side of the units making up the macrocycle and hydrophilic groups attached to the other side. These amphiphilic macrocyclic derivatives have the ability to self-assemble in aqueous solvent forming micelles or vesicles and can be used as hosts for the solubilisation and/or stabilisation of various compounds. Embodiments of the present invention utilise macrocyclic oligosaccharides and preferably cyclodextrin as the macrocyclic derivatives to be modified.

Abstract: The present invention relates, in general, to lipid A 4′ kinase and, in particular, to a nucleic acid encoding lipid A 4′ kinase and to a method of producing lipid A 4′ kinase recombinantly using same. The invention further relates to methods of producing 4′ phosphorylated lipid A analogs using the recombinantly produced lipid A 4′ kinase.

Abstract: The present invention provides a method of biasing the immune response of a mammal toward a desired epitope of a chosen antigen, particularly a functionally-relevant epitope. In preferred embodiments, the epitope-biasing method leads to fully-human antibodies of defined specificity with affinities of 10 nM to 50 pM. The invention further provides antibody libraries biased to tissues and to cell types, for use in generating epitope expression profiles useful for characterizing unknown genes. When all aspects of the present invention are combined, they result in an integrated system for defining critical epitopes on newly discovered gene products and rapidly devloping therapeutic grade antibodies to those critical epitopes.

Abstract: Oligosaccharides including those usable as anti-inflammatory agent or anti-allergy agent, represented by the following general formula (3): wherein R10 and R11 each independently represent a hydrogen atom or —SO3M where M represents a proton or a monovalent cation, Ac represents an acetyl group, R12 represents a hydrogen atom or an anomeric substituent (a 6-O-sulfated N-acetylglucosamine residue, an alkyl group, a glycerol residue, an O-alkylglycerol residue, a cholesterol residue, a cholestanyl group, a ceramide residue, a phospholipid residue, a biotin residue, or a peptide residue), and Z represents an oxygen atom or —NHCO—.

Abstract: A sialyltransferase having the following physico-chemical properties;

Abstract: A biologically active conjugate is disclosed comprising a biopolymer and a therapeutic agent joined by a disulfide bond. The conjugate, when formulated in a pharmaceutical composition with a suitable carrier, has improved in vivo stability and activity, and can be targeted to a variety of cells, tissues and organs.

Abstract: The present invention provides bioconjugates comprising substances which provide increased safety and bioavailability of nucleic acids when used in gene therapy applications. The dihydrazide derivatized hyaluronic acid/nucleic acid compositions of the present invention include hyaluronic acid which has been derivatized with a dihydrazide, preferably adipic dihydrazide, which is crosslinked to a nucleic acid. These compositions may be included in microsphere, film, wafer, matrix, hydrogel, gel and sol formulations. These bioconjugates are useful in gene therapy applications for the treatment of a variety of medical conditions including dry eye syndrome or other medical conditions wherein an increase in the production of hyaluronic acid in the eye would be therapeutic. Further, there may be other medical conditions which could benefit from increased production of hyaluronan, such as osteoarthritis of the articular joints.

Abstract: The invention relates to the use of the disaccharide derivatives 3′-aminosucrose, sucrose-C6-acid and palatinose-C6′-acid and/or of an amide or alkyl ester thereof for the prevention or treatment of hyperglycemias.

Abstract: The invention relates to the use of the disaccharide derivatives 3′-aminosucrose, sucrose-C6-acid and palatinose-C6′-acid and/or of an amide or alkyl ester thereof for the prevention or treatment of hyperglycemias.

Abstract: An outer layer having an entanglement comprising an intermingling of cloaked hydrophilic guest and a hydrophobic polymer host, wherein molecules of the guest have been crosslinked with each other. Under certain circumstances, using complexes of the guest may be desirable or even necessary. The intermingling of the guest and host includes a physical tangling, whether it also comprises crosslinking by primary bonding (e.g., chemical/covalent bonding) there-between. Also a method of producing an outer layer having such an entanglement, including the steps of: temporarily cloaking at least a portion of the hydrophilic groups of the guest; intermingling at least a portion of the cloaked groups with a porous polymeric structure by diffusing the guest with cloaked groups into at least a portion of the structure's pores; within the pores, crosslinking at least a portion of the molecules of the guest with the guest; and removing the cloaking. Cloaking may be performed by silylation or acylation.

Abstract: Vaccine conjugates are described comprising a capsular polysaccharide antigen conjugated to a carrier molecule, which carrier molecule is a protein associated with iron uptake by pathogenic microorganisms. The vaccine conjugate may comprise second or additional antigens also conjugated to the carrier. In a preferred embodiment, the carrier is a transferrin binding protein, in particular TbpA or TbpB. Also described are methods for conjugating the antigen/s to the carrier molecule, and to the use of transferrin binding protein in the manufacture of a carrier-antigen conjugate for vaccination. Affinity matrices comprising immobilised ligand for an iron uptake protein, and the use thereof for purifying a vaccine conjugate according to the present invention are also described.

Abstract: The present invention provides novel &agr;-O-linked glycoconjugates such as &agr;-O-linked glycopeptides, as well convergent methods for synthesis thereof. The general preparative approach is exemplified by the synthesis of the mucin motif commonly found on epithelial tumor cell surfaces. The present invention further provides compositions and methods of treating cancer using the &agr;-O-linked glycoconjugates.

Abstract: The present invention relates to methodology for polymer grafting by a polysaccharide synthase and, more particularly, polymer grafting using the hyaluronate synthase from Pasteurella multocida. The present invention also relates to coatings for biomaterials wherein the coatings provide protective properties to the biomaterial and/or act as a bioadhesive. Such coatings could be applied to electrical devices, sensors, catheters and any device which may be contemplated for use within a mammal. The present invention further relates to drug delivery matrices which are biocompatible and may comprise combinations of a biomaterial or a bioadhesive and a medicament or a medicament-containing liposome. The biomaterial and/or bioadhesive is a hyaluronic acid polymer produced by a hyaluronate synthase from Pasteurella multocida.

Abstract: Chimeric human antibody expression vectors are constructed by inserting the antibody heavy chain variable region-encoding cDNA and antibody light chain variable region-encoding cDNA isolated from hybridomas producing a mouse or rat monoclonal antibody reacting with the ganglioside GM2 respectively into an expression vector for use in animal cells which contains the human antibody heavy chain constant region- or human antibody light chain constant region-encoding cDNA. The expression vectors are introduced into animal cells and the transformant thus obtained is cultured for the production of a chimeric human antibody reacting with the ganglioside GM2.

Abstract: Crosslinked compounds of hyaluronic acid and the derivatives thereof, prepared by the technique of precipitation induced by supercritical antisolvent (SAS), can be used to advantage for the preparation of biomaterials for use in the field of medicine and surgery and in tissue engineering for medical and surgical purposes.

Abstract: A processes for preparing crystalline clindamycin free base is provided.

Abstract: The antibiotic drug clindamycin is provided as a crystalline free base. Three polymorphic/pseudopolymorphic forms of crystalline clindamycin free base are disclosed. Also provided are pharmaceutical compositions comprising crystalline clindamycin free base. Processes for preparing crystalline clindamycin free base and compositions thereof are also provided along with methods for treating medical conditions with the pharmaceutical compositions.

Abstract: The present invention is directed to N-acetyl-D-glucosamine obtained from microbial biomass, and to methods of obtaining N-acetyl-D-glucosamine from microbial biomass. In particular, the present invention is directed to the use of fungal biomass to create N-acetyl-D-glucosamine. The N-acetyl-D-glucosamine is efficiently obtained at high purity by degrading chitin in the fungal biomass to create N-acetyl-D-glucosamine.

Abstract: A processes for preparing crystalline clindamycin free base is provided.

Abstract: The invention provides methods and compositions useful for making synthetic peptide conjugates.

Abstract: The present invention describes a combined vaccine that offers broad protection against meningococcal disease caused by the pathogenic bacteria Neisseria meningitidis. The vaccine is comprised of four distinct polysaccharide-protein conjugates that are formulated as a single dose of vaccine. Purified capsular polysaccharides from Neisseria meningitidis serogroups A, C, W-135, and Y are chemically activated and selectively attached to a carrier protein by means of a covalent chemical bond, forming polysaccharide-protein conjugates capable of eliciting long-lasting immunity to a variety of N. meningitidis strains in children as well as adults.

Abstract: Reagents and methods for the detection of Staphylococcus aureus are provided. The reagents contain an antibody that binds to a capsular polysaccharide of type 5 of Staphylococcus aureus, and can be used in methods for detection of oxacillin resistant Staphylococcus aureus that escapes detection by agglutination in the presence of fibrinogen and antibodies directed against protein A of Staphylococcus.

Abstract: A series of long chain, unbranched polylactosamine glycosphingolipids with terminally sialylated, internally polyfucosylated structures binds selectins.

Abstract: A novel medicine capable of inducing osteogenesis at lower dosage is provided. The osteogenesis inducing medicine contains a lipid-bound glycosaminoglycan, composed of a glycosaminoglycan conjugated with a lipid, or a pharmacologycally accepted salt of the lipid-bound glycosaminoglycan as the effective ingredient of the medicine.

Abstract: A solid lipophilic microparticle having an average particle size ranging from 0.1 to 200 &mgr;m, comprising a lipophilic substance, hyaluronic acid or an inorganic salt thereof and an active ingredient selected from the group consisting of a protein or peptide drug, retains the full activity of the active ingredient, and when formulated in the form of an oil dispersion or oil-in-water emulsion, it releases in an in vivo environment the active ingredient in a controlled manner over a long period.

Abstract: A method for decreasing or shortening the length of time required to complete a surgical procedure by the application of hyaluronic acid to the surgical site, and for wound management by topical application of hyaluronic acid to a wound by syringe through a thin film dressing. The method of wound management results in accelerated wound healing time. The solution of hyaluronic acid may include an effective amount of a polysulfated glycosaminoglycan for stimulating macrophage activity at the surgical wound site.

Abstract: The present invention discloses improved lysophospholipids composition having water-solubility in order to solve a conventional problem accompanying only the use of LPE as an anti-aging lysophospholipid caused by water-insoluble property thereof, comprising subsidiary lysophospholipid components, that is, LPI and LPC other than LPE to inhibit aging processional lysophospholipids, thereby forming an enhanced water-soluble lysophospholipids composition conveniently useable in plants and/or animals applications.

Abstract: Disclosed are derivatives of glycopeptide compounds having at least one substituent of the formula:

Abstract: This invention describes a method for preparing water-insoluble biocompatible gels, films and sponges by reacting hyaluronic acid, or a salt thereof, with a carbodiimide in the absence of a nucleophile or a polyanionic polysaccharide. The water-insoluble gels, films and sponges of this invention may be used as surgical aids to prevent adhesions of body tissues and as drug delivery vehicles.

Abstract: The structure and specificity of a recombinant &agr;2,3-sialyltransferase from Campylobacter spp., is disclosed. Also provided are methods for using the &agr;2,3-sialyltransferase in the production of desired carbohydrate structures and nucleic acids that encode the sialyltransferase.

Abstract: The present invention comprises a method for detecting antiglycolipid autoantibodies in a subject who has or who may develop an autoimmune neuropathy. The present invention comprises a method for detecting antiganglioside autoantibodies in a subject. The present invention also provides methods for detecting multiple antiganglioside autoantibodies in a subject, simultaneously or consecutively. The present invention also provides methods for quantitating ganglioside autoantibodies in a subject. The present invention also provides a method of diagnosing autoimmune neuropathy in subjects with peripheral neuropathies. The present invention also provides a method of diagnosing autoimmune neuropathy in celiac disease in a subject.

Abstract: Disclosed is a method for preparing a malto-oligosaccharide derived glycoside. Generally, the method comprises providing a malto-oligosaccharide and glycosylating the malto-oligosaccharide with an alcohol or a thiol under conditions suitable to form a malto-oligosaccharide derived glycoside. Also disclosed is a method for preparing a mixture of malto-oligosaccharide derived glycosides by providing a mixture of malto-oligosaccharides and glycosylating the malto-oligosaccharides with an alcohol or a thiol under substantially anhydrous conditions to form a mixture of malto-oligosaccharide derived glycosides.

Abstract: Modified polysaccharides (such as starches, gums, chitosans, celluloses, alginates, sugars, etc.), which are commonly used in the paper industry as strengthening agents, surface sizes, coating binders, emulsifiers and adhesives, can be combined into a single molecule with amphiphilic hydrocarbons (e.g. surface active agents) which are commonly utilized in the paper industry to control absorbency, improve softness, enhance surface feel and function as dispersants. The resulting molecule is a modified polysaccharide having surface active moieties which can provide several potential benefits, depending on the specific combination employed, including: (a) strength aids that do not impart stiffness; (b) softeners that do not reduce strength; (c) wet strength with improved wet/dry strength ratio; (d) debonders with reduced Tinting and sloughing; (e) strength aids with controlled absorbency; and (f) surface sizing agents with improved tactile properties.

Abstract: The invention provides methods for purifying carbohydrates, including oligosaccharides, nucleotide sugars, and related compounds, by use of ultrafiltration, nanofiltration and/or reverse osmosis. The carbohydrates are purified away from undesired contaminants such as compounds present in reaction mixtures following enzymatic synthesis or degradation of oligosaccharides.

Abstract: Herein is disclosed a method for producing lipopolysaccharide (LPS), comprising: (a) growing a culture of a deep rough mutant bacterial strain in a medium; (b) maintaining the culture in stationary phase for at least about 5 hr; (c) harvesting cells from the culture; and (d) extracting LPS from the cells. The method allows for the production of an LPS which can be used to produce a 3-O-deacylated monophosphoryl lipid A (3D-MLA) having at least about 20 mol % of the hexaacyl congener group.

Abstract: A process is described for preparing a substrate for the transglycosylase enzymes of bacterial cell wall biosynthesis. The chemical synthesis makes available a sustainable and substantially pure source of supply of lipid II, including analogs thereof, that may be used in the identification of new therapeutic agents capable of disrupting steps in bacterial cell wall biosynthesis.

Abstract: A compound of formula (I) below, which exhibits excellent macrophage activity inhibitory action, is useful for the treatment or prophylaxis of inflammatory disorders, autoimmune diseases or septicemia. In a preferred embodiment, R1 and R3 each represents a C1-C20 alkanoyl group which may optionally be substituted with one or more substituent groups selected from substituent group A, R2 and R4 each represents a C1-C20 alkyl group which may optionally be substituted with one or more substituent groups selected from substituent group A, R5 is a hydrogen atom, a halogen atom, a hydroxy group, or a C1-C6 alkoxy group, and substituent group A is a halogen atom, a hydroxy group, an oxo group, a C1-C20 alkoxy group, or a C1-C20 alkanoyloxy group.

Abstract: The present invention is drawn to a pharmaceutical composition, comprising a pharmaceutically effective amount of an acidic polysaccharide and/or a derivative thereof, a gaseous vehicle, and a pharmaceutically acceptable carrier or excipient. Said acidic polysaccharide or derivative thereof can be hyaluronic acid, a pharmaceutically acceptable salt of hyaluronic acid, a partial or total ester of hyaluronic acid with an alcohol, a partial or total intermolecular ester of hyaluronic acid, a partial or total intramolecular ester of hyaluronic acid, a cross-linked ester of hyaluronic acid, an alginic acid ester, an ester of carboxymethylcellulose, an ester of carboxymethylchitin, an ester of carboxymethyl starch, a gellan ester, a cross-linked gellan ester, a pectic acid ester, and a pectinic acid ester. The composition can contain one or more topical drugs, and can be in the form of an aerosol or liquid spray, a foam, or a dry spray.

Abstract: Libraries are synthesized with oligomeric carbopeptoids and carbonucleotoids. Carbopeptoids are oligosaccharides having carbohydrate subunits linked to one another by amide bonds. Carbonucleotoids are oligosaccharides having carbohydrate subunits linked to one another by phosphodiester bonds. Carbopeptoid libraries may be fabricated using automated polypeptide synthesizers. Carbonucleotoid libraries may be fabricated using automated polynucleotide synthesizers.

Abstract: Reagents and methods are provided for crosslinking and immobilizing biomolecules, drugs and synthetic polymers. The reagents possess (i) a thiol or amino reactive group; and (ii) a hydrazino or oxyamino moiety. Conjugates and immobilized biomolecules are also provided.

Abstract: The invention provides methods for inhibiting immune responses by inhibiting the biosynthesis of the sialyl galactosides that are involved in immune responses. In particular, B lymphocyte-mediated immune responses are mediated by interfering with synthesis of &agr;2,6 sialylgalactosides, while T lymphocyte-mediated immune responses are inhibited by blocking synthesis of &agr;2,3 sialylgalactosides. The inhibition is accomplished by, for example, inhibiting the activity of a glycosyltransferase involved in synthesis of the respective sialyl galactoside.

Abstract: The invention provides a composition containing particulate composite of a polymer and a therapeutic agent. The composition also contains a complexing agent. The polymer interacts with the complexing agent in a host-guest or a guest-host interaction to form an inclusion complex. A therapeutic composition of the invention may be used to deliver the therapeutic agent and to treat various disorders. Both the polymer of the particulate composite and the complexing agent may be used to introduce functionality into the therapeutic composition. The invention also relates to a method of preparing a composition. The method combines a therapeutic agent, a polymer having host or guest functionality, and a complexing agent having guest or host functionality to form the therapeutic composition. The complexing agent forms an inclusion complex with the polymer. The invention also relates to a method of delivering a therapeutic agent.

Abstract: Orthomolecular Vitamin E derivative compounds, compositions, and their uses for effecting aging and longevity, nerve activity, hematopoiesis and maintenance of blood cells, hepatic activity, nephritic activity, heart and cardiovascular function, pulmonary function, muscular function, cartilage, bone, and joint health, gastrointestinal function, reproductive system function, vision, immune function, cell membrane integrity, and pain and inflammation; preventing or treating diseases or conditions; treating cancers or obesity; and reducing the risk of Sudden Infant Death Syndrome in an animal.

Abstract: A method for treatment of a diabetic condition, wherein a therapeutically effective amount of at least one isoform of sulfatide is administered to a patient, wherein said at least one isoform of sulfatide upon administration to the patient affects the sulfatide metabolism in such a way that it results in an increased amount of sulfatide.

Abstract: A method for the laboratory determination of prosthetic infections is described. This method, performed on biological fluids isolated from patients, is based on the detection of antibodies specific for the polysaccharides produced by bacteria colonizing prosthetic devices.

Abstract: Randomly generated glycopeptide combinatorial libraries are generated by randomly glycosylating a peptide having at least one glycosylation site with at least one glycosyl donor, optionally blocking unreacted glycosylation sites on the glycopeptides and optionally selectively removing one or more protecting groups on the carbohydrate groups introduced at the first level; whereby a first level library of glycopeptides is created; and then optionally randomly glycosylating said first level library of glycopeptides, or a combination of first level libraries of glycopeptides, with at least one glycosyl donor, and optionally selectively removing one or more designated protecting groups on the carbohydrate groups introduced at the second level; whereby a second level library of glycopeptides is created. Further iterations of the process result in higher level libraries of increased diversity. The glycopeptide libraries including, e.g.

Abstract: Fluorescent biosensor molecules, fluorescent biosensors and systems, as well as methods of making and using these biosensor molecules and systems are described. Embodiments of these biosensor molecules exhibit fluorescence emission at wavelengths greater than about 650 nm. Typical biosensor molecules include a fluorophore that includes an iminium ion, a linker moiety that includes a group that is an anilinic type of relationship to the fluorophore and a boronate substrate recognition/binding moiety, which binds glucose. The fluorescence molecules modulated by the presence or absence of polyhydroxylated analytes such as glucose. This property of these molecules of the invention, as well as their ability to emit fluorescent light at greater than about 650 nm, renders these biosensor molecules particularly well-suited for detecting and measuring in-vivo glucose concentrations.

Abstract: The invention relates to the formulation of pharmaceutical compounds. More particularly, the invention provides stable, pharmaceutically acceptable compositions prepared from boronic acid compounds and methods for preparing the compositions. The invention also provides novel boronate ester compounds. The invention further provides boronic acid anhydride compounds useful in the methods of the invention.

Abstract: A process for purifying high molecular weight hyaluronic acid from a biological source, including the steps of adjusting the pH of an aqueous solution containing high molecular weight hyaluronic acid from a biological source to a pH in the range from 1.7 to 3.3 and then diafiltering said aqueous solution at the same pH using a filter having a pore size in the range from 100,000 Daltons nominal molecular cut-off to 0.45 m, and of removing cells from the aqueous solution containing high molecular weight hyaluronic acid from biological source.

Abstract: The present invention has determined that exogenously added glycosylceramide (GlcCer) and other neutral glycolipids such as the homologous Glc-containing globotriaosylceramide (Gb3Cer), dose-dependently prolonged clotting times of normal plasma in the presence but not absence of APC:protein S, indicating GlcCer or Gb3Cer can enhance protein C pathway anticoagulant activity. In studies using purified proteins, inactivation of factor Va by APC:protein S was enhanced by GlcCer alone and by GlcCer, globotriaosylceramide, lactosylceramide, and galactosylceramide in multicomponent vesicles containing phosphatidylserine and phosphatidylcholine. Thus, the present invention provides neutral glycolipids such as GlcCer and Gb3Cer, as anticoagulant cofactors that contribute to the antithrombotic activity of the protein C pathway. The present invention has also determined that a deficiency of plasma GlcCer is a risk factor for thrombosis.