Abstract: The present invention relates generally to hydrolyzable drug-oligomer conjugates, pharmaceutical compositions comprising such conjugates, and to methods for making and using such conjugates and pharmaceutical compositions. For example, a conjugate of insulin, PEG, and oleic acid can be orally administered.

Abstract: This invention pertains to solid-phase oligosynthesis, and more particularly to universal solid supports for solid-phase oligonucleotide synthesis, methods for their preparation, and methods for their use. One aspect of the invention pertains to a method for the preparation of a universal solid support suitable for use in solid-phase oligosynthesis, which method comprises the steps of: (a) reacting a pendant functional group (e.g., —NH2) of a solid support (e.g., CPG) with a linker reagent (e g., oxalyl chloride), thereby forming a pendant linker group (e.g., —C(═O)Cl); (b) removing at least a portion of excess unreacted linker reagent by evaporation (e.g., using a rotavapor apparatus); and, (c) reacting said pendant linker group with a cyclic reagent (e.g., protected inosine), thereby forming a pendant cyclic group.

Abstract: A method and device for sequencing at least a fragment of a linear polymer. The device comprises a well for placement of a rotaxane comprising the combination of a cyclic molecule and a linear polymer threaded through said cyclic molecule; a probe having the ability to move the linear polymer relative to the cyclic molecule while producing a signal resulting from the interaction of the cyclic molecule and a unit attached to the polymer; and means for reading said signal. The process comprises formation of the rotaxane, attachment of the probe, movement of the cyclic molecule relative to the linear polymer and the reading of signals. The device and method are especially useful for the sequencing of DNA.

Abstract: Method and reagent composition for covalent attachment of target molecules, such as nucleic acids, onto the surface of a substrate. The reagent composition includes epoxide groups capable of covalently binding to the target molecule. Optionally, the composition can contain photoreactive groups for use in attaching the reagent composition to the surface. The reagent composition can be used to provide activated slides for use in preparing microarrays of nucleic acids.

Abstract: The invention concerns an electroactive complex, consisting of an electroactive homopolymer or copolymer polymer of at least two monomers, and anti-ligand and a ligand having specifically interacted with said antiligand, and further at least an electron donor group, and an electroactive probe, consisting of said polymer said antiligand capable of interacting specifically with said ligand and at least an electron donor group.

Abstract: Cellulosic polymers, copolymers and grafts, are disclosed that adhere to fibers and surfaces during an aqueous treatment process. The cellulosic polymers having grafts and/or co-blocks are prepared using living-type free radical polymerization techniques, which provides control over the degree of substitution and graft/co-block composition and structure. These cellulosic polymers allow for the modification of fibers and surfaces to provide a desired effect.

Abstract: The invention concerns a polymer derived from a polysaccharide copolymer consisting of a main chain comprising several similar or different anhydrohexose units, and branches comprising at least a neutral or anionic anhydropentose and/or anhydrohexose unit; said polymer derivative comprising one or several units bearing an oxime function at least on position C2. Furthermore, the polymer is obtainable by carrying out the following steps: a) contacting a polysaccharide with an aqueous solution comprising at least an oxidising agent for oxidising at least the hydroxyl radical borne by the carbon C2 of one or several units, into a ketone function; b) contacting the resulting polymer with hydroxylamine or a derivative to transform the ketone function into an oxime function. The invention also concerns a polymer obtainable by carrying out a step c) which consists in contacting the polymer having at least an oxime function at least on position C2 of said unit, with an agent reducing the oxime function.

Abstract: We describe pH-sensitive endosomolytic polymers, delivery particles containing pH-sensitive endosomolytic polymers. The described particles are capable of delivering polynucleotides to cells from the peripheral circulation with subsequent release from endosomes. The endosomolytic polymers are inactive outside the cell but disrupt membranes upon exposure to an acidified endosomal compartment.

Abstract: This invention discloses a method for preparing a complex comprised of a VEGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound by identifying a VEGF Nucleic Acid Ligand by SELEX methodology and associating the VEGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further discloses Complexes comprising one or more VEGF Nucleic Acid Ligands in association with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further includes a Lipid construct comprising a VEGF Nucleic Acid Ligand or Complex and methods for making the same.

Abstract: The present invention relates to polymerizable monomers for applications in medicine and biotechnology and synthesis thereof. The polymerizable ligands containing NAcetyl Glucosamine bind more strongly to lysozyme than NAG itself. The binding is further enhanced when a spacer arm, for example 6-Amino Caproic Acid (6-ACA) is introduced in the structure.

Abstract: The present invention provides positively chargeable biodegradable copolymers composed of a low molecular weight polycationic copolymer polyethylenimine linked by cyclodextrin, a method for the copolymer synthesis and the method of using the copolymers for intracellular delivery of nucleic acid molecules. The copolymers comprise ester bonds for hydrolysis and positively charged amines for forming complexes with negatively charged nucleic acids. The copolymers of the invention are useful as delivery systems of therapeutic genetic materials for gene therapy.

Abstract: The present invention provides amphiphilic prodrugs comprising a therapeutic compound conjugated to an PEG-oligomer/polymer and methods for using said prodrugs to enable oral drug delivery and/or delivery of drugs across the blood brain barrier into the central nervous system.

Abstract: Cationic starch graft copolymer composed of the monomers a) to d)

Abstract: A modified solid carrier composed of a solid carrier and a group of compounds having a vinylsulfonyl group which are fixed to the solid carrier with non-covalent bonding is favorably employed for preparing a device for detection of oligonucleotide or polynucleotide.

Abstract: PEG-chitosan conjugates comprising chitosan and polyethylene glycol moieties or derivatives thereof which are bonded together and their use in medicine is described. In one embodiment, the conjugate comprises a chitosan moiety or a derivative thereof and a polyethylene glycol moiety or a derivative thereof which are bonded together via the amino function on the chitosan by the use of an activated chitosan species. In another embodiment, the conjugate comprises a chitosan moiety or a derivative thereof and a polyethylene glycol moiety or a derivative thereof which are bonded together, the chitosan portion of the conjugate having a molecular weight in the range of from 10 kilodaltons to 1000 kilodaltons.

Abstract: The invention provides a multi-arm block copolymer for use in delivering a variety of bioactive agents. The copolymer of the invention contains a central core from which extend multiple (3 or more) copolymer arms. Each copolymer arm possesses an inner polypeptide segment and an outer hydrophilic polymer segment. Thus, the overall structure of the copolymer comprises an inner core region that includes the central core and the inner polypeptide segment, while the outer core region is hydrophilic in nature. The multi-arm copolymer of the invention is particularly useful for delivery of biologically active agents that can be entrapped within the inner core region.

Abstract: The present invention relates to a nucleic acid binding polymer which has affinity for nucleic acid molecules such as DNA, RNA, or hybrids thereof. The polymer is comprised of a nucleic acid binding backbone linked to a nucleic acid binding agent, preferably by a linking moiety. The polymer can be used to isolate and purify nucleic acid molecules from a variety of sample types including but not limited to clinical and environmental.

Abstract: The invention relates to absorbent polymers based on optionally partially neutralised, monoethylenically unsaturated, acid group-carrying monomers. The surfaces of said polymers are re-cross-linked. The inventive polymers also have cyclodextrines and/or cyclodextrine derivatives which are covalently and/or ionically bonded and/or included therein.

Abstract: High molecular weight derivatives of activated poly(ethylene glycol) and the like polymers are prepared in high purity by conjugating a large PEG molecule to a small PEG molecule. Most of the reaction steps can be accomplished on the more readily purified small molecule to avoid laborious purification of the high molecular weight derivatives.

Abstract: The present invention relates to compositions and methods involving biocompatible dendrimers. In particular, the present invention provides dendrimeric copolymers with poly(propyleneimine) (POPAM) interiors and poly(amidoamine) (PAMAM) exteriors for use in transfection and imaging applications.

Abstract: A dihydroxyphenyl cross-linked macromolecular network is provided that is useful in artificial tissue and tissue engineering applications, such as artificial or synthetic cartilage. The network is made by first providing a polyamine or polycarboxylate macromolecule (having a plurality of amine or carboxylic acid groups respectively attached along the length of the molecule), reacting this macromolecule with a hydroxyphenyl compound having a free carboxylic acid group in the case of a polyamine or a free primary amine group in the case of a polycarboxylate, and substituting the hydroxyphenyl compound onto the macromolecule via a carbodiimide-mediated reaction pathway to provide a hydroxyphenyl-substituted macromolecule. This macromolecule is then linked to other such macromolecules via an enzyme catalyzed dimerization reaction between two hydroxyphenyl groups attached respectively to different macromolecules under metabolic conditions of temperature and pH.

Abstract: A biodegradable cationic lipopolymer comprising a polyethylenimine (PEI), a lipid, and a biocompatible hydrophilic polymer, wherein 1) the lipid and the biocompatible hydrophilic polymer are directly linked to the PEI backbone or 2) the lipid is linked to the PEI backbone through the biocompatible hydrophilic polymer. The cationic lipopolymers of the present invention can be used for delivery of a nucleic acid or any anionic bioactive agent to various organs and tissues after local or systemic administration.

Abstract: The invention relates to a system, which can be used for measuring membrane permeation in substances. Said system comprises, essentially, porous particles with an inner surface formed within the pores, and another outer surface. Essentially, only the outer surface is fully covered by a lipid layer, said lipid layer extending over the openings of the pores on the outer surface. Preferably, an intermediate layer is arranged between the outer surface and the lipid layer. Said intermediate layer is embodied, more particularly, in the form a polymer network.

Abstract: Anionic, hydrophobic polysaccharides useful as soil release agents in detergent compositions are graft copolymers of a polysaccharide having anionic substituents with an ethylenically unsaturated monomer, the copolymer having a polysaccharide backbone carrying grafted hydrophobic vinyl polymeric groups derived from the ethylenically unsaturated monomer, and anionic substituents. The polymers exhibit enhanced release of both oily and particulate soil from both polyester and cotton.

Abstract: Methods of preparing vancomycin-polymer conjugates are disclosed. In preferred aspects, polymer residues which are preferably releasable, are selectively attached to the sugar amino and/or N-methyl amino groups of vancomycin and related compounds. Vancomycin-polymer conjugates made by the methods and methods of treatment using the conjugates are also disclosed.

Abstract: Methods of preparing peptide linked oligomeric compounds are provided. The method is useful for preparing larger scale amounts of peptide linked oligomeric compounds. More particularly, the synthesis of peptide linked oligomeric compounds is performed without the problems of aggregation associated with electrostatic interactions. The present method describes using equimolar amounts of oligomeric compounds and peptide reagents providing for an increase in overall efficiency.

Abstract: Novel dendritic polymers are employed to clinically seal or repair wounds and treat traumatized or degenerative tissue. Novel crosslinkable biopolymers such as dendritic macromolecules are used in vitro, in vivo and in situ to treat ophthalmological, orthopaedic, cardiovascular, plastic surgery, pulmonary or urinary wounds or injuries. The crosslinkable dendritic macromolecules can be fabricated into cell scaffold/gel/matrix of specified shapes and sizes using one-photon and multi-photon spectroscopic techniques. The crosslinked polymers can be seeded with cells and used to repair or replace organs, tissues or bones. Alternatively, the polymers and cells can be mixed and injected into the in vivo site and crosslinked in situ for organ, tissue or bone repair or replacement.

Abstract: A method for the separation of polysaccharides. The method comprises conjugating a ligand to a thermo-sensitive polymer to form a conjugate, wherein the ligand specifically recognizes a polysaccharide, and the thermo-sensitive polymer features a lower critical solution temperature (LCST), contacting a mixture containing a desired polysaccharide with the conjugate at an environmental temperature lower than the LCST to form a polysaccharide-conjugate complex, collecting the polysaccharide-conjugate complex at an environmental temperature higher than the LCST, and releasing the polysaccharide from the polysaccharide-conjugate complex to obtain the desired polysaccharide.

Abstract: The present invention provides a process for the production of hyaluronic acid (HA) derivatives cross-linked with another polymer, in particular multiple e.g. double cross-linked hyaluronic acid derivatives. The invention also provides novel cross-linked derivatives, products containing them and their uses in cosmetic, medical and pharmaceutical applications.

Abstract: The present invention involves a series of articles, compositions, methods, and kits. Some aspects of the invention include articles such as particles, sols, blends, dispersions, films, or microarrays that comprise luminescent polymers, as well as methods for making and using such articles. In some cases, the luminescent polymer may be characterized in part by having a delocalized &pgr;-orbital structure, which can allow the polymer to have a high degree of luminosity. The polymers of this invention may also have, in some embodiments, bulky substituents to prevent intermolecular &pgr;-&pgr; interactions that can decrease luminosity. Some articles may include more than one luminescent polymer, for example, a first polymer that absorbs energy and directs the energy to a second polymer that releases the energy.

Abstract: The present invention relates to compositions and methods involving biocompatible dendrimers. In particular, the present invention provides dendrimeric copolymers with poly(propyleneimine) (POPAM) interiors and poly(amidoamine) (PAMAM) exteriors for use in transfection and imaging applications.

Abstract: The present invention relates to activated biocompatible non-antigenic copolymers formed by copolymerizing polyethyleneimine with biocompatible polymer other than polyethyleneimine, biologically active non-antigenic conjugates formed by binding said copolymers to biologically active materials such as drugs or proteins. A biologically active non-antigenic conjugate of the present invention has a characteristic feature in that its constitutive copolymer essentially consists of hydrophilic polymer, which plays a role to provide high stability and long in vivo half-life of the hydrophobic drugs or proteins, and positively charged polymer which functions to increase the cellular uptake of the drugs or proteins.

Abstract: New compounds, compositions and methods which find application in solid phase synthesis including the preparation of high-density arrays of diverse polymer sequences such as diverse peptides and oligonucleotides as well as in preparation of arrays of small ligand molecules. The compounds of the present invention are those which are typically referred to as linking groups, linkers or spacers and include unsymmetrical disulfide linking groups, and 1,3-diol derivatives capable of providing a triggered release of an attached compound from a solid support under mild conditions. Additional new compounds are labels which can be incorporated into either the 3′ or 5′ terminus of a DNA oligomer.

Abstract: This invention pertains to solubility enhanced polymers and methods, kits and compositions which enhance the aqueous solubility of said polymers. One set of preferred methods, kits and compositions embody or utilize phosphorous containing synthons and are most useful for modulating the solubility of synthetic nucleic acids and synthetic nucleic acid analogs. A second set of preferred methods, kits and compositions are most useful for modulating the aqueous solubility of peptides, other polyamides and most preferably peptide nucleic acid (PNA) polymers.

Abstract: An antiviral compound comprises a linear non-carbohydrate polymer having a plurality of side chain groups, wherein at least one of the side chain groups has an anionic- or cationic-containing moiety bonded or linked thereto.

Abstract: The invention provides compositions comprising formula 1 steroids, e.g., 16&agr;-bromo-3&bgr;-hydroxy-5&agr;-androstan-17-one hemihydrate and one or more excipients, typically wherein the composition comprises less than about 3% water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16&agr;-bromo-3&bgr;-hydroxy-5&agr;-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen (viral) replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using certain steroids and steroid analogs. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

Abstract: The present invention relates to improved methods for reducing pain and organ dysfunction using bioadhesive, bioresorbable, anti-adhesion compositions made of intermacromolecular complexes of carboxyl-containing polysaccharides, polyethers, polyacids, polyalkylene oxides, multivalent cations and/or polycations. The polymers are associated with each other, and are then either dried into membranes or sponges, or are used as gels, fluids or microspheres. Compositions are useful in surgery to prevent the formation and reformation of post-surgical adhesions. The compositions are designed to breakdown in-vivo, and thus be removed from the body. Membranes are inserted during surgery either dry or optionally after conditioning in aqueous solutions.

Abstract: The invention concerns a biocompatible polymer having a mole weight more than 50000 g/mole, preferably 90000 g/mole for fixing biological ligands comprising at least a first linear segment consisting of a hydrophobic homopolymer derived from polymerisation of a hydrophobic monomer A; a second linear segment consisting of a hydrophilic polymer derived from copolymerisation of a monomer B bearing a reactive function X and a hydrophilic monomer C not bearing any reactive function, said second segment being covalently bound to one end of the first segment. The invention also concerns a biological polymer-ligand-conjugate, a device for capturing a target molecule comprising a solid support whereon is immobilised a biological polymer-ligand conjugate and methods for preparing said polymer. The invention is mainly applicable in the field of diagnosis.

Abstract: A polymer having a plurality of 5-6 membered unsaturated rings which may be the same or different, linked together by way of linker chains to form a backbone, at least some of said 5-6 membered unsaturated rings carrying a ligand. Polymers of this nature can act as DNA mimics and as supports for use in oligonucleotide production.

Abstract: A nucleic acid complex for delivering a nucleic acid or a derivative thereof to a cell comprises the components: A. a nucleic acid or a derivative thereof; B. a cationic polymer; and C. a preformed polyethylene glycol-cationic polymer copolymer. The complex has a conformation in which the nucleic acid or derivative thereof is condensed and wherein component C is bound to component A such that the poylethylene glycol groups of component C are located at the surface of the complex. The complexes which are stable to aggregation are useful for the delivery of nucleic acids or derivatives thereof to cells in biological systems.

Abstract: This application discloses compositions of carbohydrate-modified polymers, such as polyethylenimine modified with cyclodextrin moieties, for carrying drugs and other active agents, such as nucleic acids. Compositions are also disclosed of carbohydrate-modified polymer carriers that release such agents under controlled conditions. The invention also discloses compositions of carbohydrate-modified polymer carriers that are coupled to biorecognition molecules for targeting the delivery of drugs to their site of action.

Abstract: Disclosed are methods of conjugating biologically active substances, particularly, alpha-interferon, with a hyaluronan or a mixture of a hyaluronan with at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone. Also disclosed are stable intermediates formed by partially reacting a hyaluronan with divinyl sulfone and stopping the reaction before completion to leave free, or reactive vinyl groups on the hyaluronan molecule available for conjugation with the biologically active substance.

Abstract: PEG-chitosan conjugates comprising chitosan and polyethylene glycol moieties or derivatives thereof which are bonded together and their use in medicine is described. In one embodiment, the conjugate comprises a chitosan moiety or a derivative thereof and a polyethylene glycol moiety or a derivative thereof which are bonded together via the amino function on the chitosan by the use of an activated chitosan species. In another embodiment, the conjugate comprises a chitosan moiety or a derivative thereof and a polyethylene glycol moiety or a derivative thereof which are bonded together, the chitosan portion of the conjugate having a molecular weight in the range of from 10 kilodaltons to 1000 kilodaltons.

Abstract: A compound of formula A—B—D—X—D′—E or formula A—B—D—E—D′—X wherein A is the residue of a solid support, originating from standard materials applied in solid phase and solution phase organic chemistry, B is a linker residue having a group which allows cleavage of a compound of a formula II or a compound of formula III to liberate an D—X—D′—E, or D—E—D′—X fragment, respectively, D and D′ independently of each other are a bond or a spacer residue, E is the residue of a molecule to be investigated produced via combinatorial chemistry, and X is the residue of a fluorescent dye, which is characterized in that a compound of A—B—D—X—D′—E or of formula A—B—D—E—D′—X is tagged by at least one tag residue, and the use of such compounds in the decoding step of a screening process.

Abstract: This invention relates to hydrolytically degradable gels of crosslinked poly(ethylene) glycol (PEG) structures. Addition of water causes these crosslinked structures to swell and become hydrogels. The hydrogels can be prepared by reacting two different PEG derivatives containing functional moietes at the chain ends that react with each other to form new covalent linkages between polymer chains. The PEG derivatives are chosen to provide covalent linkages within the crosslinked structure that are hydrolytically degradable. Hydrolytic degradation can provide for dissolution of the gel components and for controlled release of trapped molecules, including drugs. Reageants other than PEG can be avoided. The hydrolysis rates can be controlled by varying atoms adjacent to the hydrolytically degradable functional groups to provide substantially precise control for drug delivery in vivo.

Abstract: The present invention relates to novel compositions of therapeutic cyclodextrin containing polymeric compounds designed as a carrier for small molecule therapeutics delivery and pharmaceutical compositions thereof. These cyclodextrin-containing polymers improve drug stability and solubility, and reduce toxicity of the small molecule therapeutic when used in vivo. Furthermore, by selecting from a variety of linker groups and targeting ligands the polymers present methods for controlled delivery of the therapeutic agents. The invention also relates to methods of treating subjects with the therapeutic compositions described herein. The invention further relates to methods for conducting pharmaceutical business comprising manufacturing, licensing, or distributing kits containing or relating to the polymeric compounds described herein.

Abstract: The invention provides a system for solid-phase synthesis of oligosaccharides, based on the discovery that a 2-substituted-1,3-dioxocycloalkyl linker group of general formula (I) can be used to couple saccharide groups of both the O-glycoside and N-glycoside type to a polymer support. The invention provides reagents, reagent kits and methods for solid-phase oligosaccharide synthesis.

Abstract: Polyamide conjugates comprising either (a) a xenoantigenic group; or (b) a biologically active group and a macromolecular, macro- or microscopic entity; bound to a polyamide backbone, processes for their preparation and the use of these conjugates in therapeutic compositions.

Abstract: This invention provides methods for purifying nucleic acids, in particular primer extension products such as those obtained in nucleic acid sequencing reactions. The methods involve the use of a primer to which is attached a string of arylboronic acid moieties. After extension of the primer using a polymerase, the primer extension-products are complexed with a solid support to which is attached an arylboronic acid complexing moiety. The resulting complex is separated from the reaction mixture, washed, and the primer extension products are dissociated from the solid support. The primer extension products are obtained in a form particularly suitable for loading directly on a capillary electrophoresis apparatus.

Abstract: A method of grafting galactomannan-type polysaccharide polymers, preferably guar, to a functional group by irradiation with high energy electron beams in the presence of an unsaturated monomer-compressing the described functional group. The method may include the depolymerization of the grafted polymer to a pre-selected low molecular weight. The preferred galactomannans for treatment according to this method are guar gum, guar splits and hydroxypropyl guar. In a preferred embodiment the guar gum is also depolymerized, preferably to a molecular weight of below about 700,000 Daltons, and most preferably to a molecular weight of between about 100,000 Daltons to about 250,000 Daltons. The depolymerized guar most preferably has a polydispersity of less than about 3.0 and is useful in oil well fracturing to enhance oil production.