Abstract: A nanoparticle including a polysiloxane base having an exterior surface and having a photosensitizer at least partly exposed at its exterior surface, said photosensitizer being secured to the exterior surface by loading the photosensitizer onto the surface after formation of the polysiloxane base of the nanoparticle. The nanoparticle may have tumor targeting moieties and may be post loaded with cyanine dye. The nanoparticle preferably includes post loaded moieties providing at least two of tumor specificity, photodynamic properties and imaging capabilities and the photosensitizer is tagged with a radioisotope. A method for preparation of the nanoparticle is also provided.

Abstract: A composition for delivering an agent to a cell, comprising a bispecific affinity reagent and a pH-responsive, membrane destabilizing polymer. The bispecific affinity reagent may include a first affinity reagent covalently linked to a second affinity reagent, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target.

Abstract: The present invention provides materials and methods for the utilization of the specific interaction of replication termination sequences with their binding proteins in molecular biology applications.

Abstract: The invention relates to an amphiphilic polymer (A) comprising repeat units of the general formulae (I), (II) and (III): or salts thereof, wherein the repeat unit of general formula (I) is comprised in the amphiphilic polymer with a number of m units, the repeat unit of general formula (II) is comprised in the amphiphilic polymer with a number of o units and repeat unit of general formula (III) is comprised in the amphiphilic polymer with a number of p units, wherein each of m, o and p is an independently selected integer from about 3 to about 400 and wherein the sum of m+o+p is selected in the range from about 10 to about 10000, R1 in repeat units (I)-(III) is H or methyl, R2 in repeat unit (II) is an aliphatic moiety with a main chain of about 3 to about 30 carbon atoms and 0 to about 3 heteroatoms selected from the group N, O, S, Se and Si, and, R3 in repeat unit (III) is one of (i) an alicyclic moiety with a main chain of about 5 to about 80 carbon atoms and 0 to about 30 heteroatoms selected from the gro

Abstract: Methods of attaching a ligand to a surface are described that include contacting a surface with a substrate containing an amphiphilic comb polymer. The substrate is configured to provide a pattern of the amphiphilic comb polymer on a selected region of the surface. The substrate can be separated from the surface leaving the amphiphilic comb polymer on the selected region of the surface, thus providing a selected region of the surface having amphiphilic comb polymer on it. A ligand can then be deposited on the surface such that the selected region of the surface having the amphiphilic comb polymer is substantially free of the ligand.

Abstract: The present invention relates to a method for producing a mature von Willebrand Factor (VWF) from von Willebrand Factor pro-peptide comprising the steps: immobilizing VWF pro-peptide on an ion exchange resin, incubating the immobilized VWF pro-peptide with furin to obtain immobilized mature VWF, and isolating mature VWF from the ion exchange resin by elution.

Abstract: An initiator for the terminal group of the polymer product of an atom or group radical transfer polymerisation has an activated carboxyl or an amine group which is reacted with an amine or carboxyl (respectively) group containing biologically active compound. The initiator is preferably 4-(3-(2-bromo, 2-methyl-propionate)phenyl)-propionic acid N-hydroxysuccinimide ester or 2-bromo, 2-methyl-propionic acid N-hydroxysuccinimide ester. The monomers preferably comprise a zwitterionic monomer such as 2-methacryloxyethyl-2?-trimethyl ammoniumethyl phosphate inner salt.

Abstract: The invention relates to a method for producing a biocompatible crosslinked gel consisting in crosslinking a determined quantity of at least one type of liquid biocompatible polymer by adding a quantity of crosslinking agent, in carrying out a crosslinking reaction, in adding an additional quantity of liquid polymer whose molecular mass is greater than 500,000 Da, in solving the reaction mixture in such a way that the total concentration of the liquid polymer is reduced, in crosslinking and in stopping the crosslinking reaction by removing the crosslinking agent. The inventive gel and the use thereof are also disclosed.

Abstract: An object to be solved by the present invention is to provide a highly reliable hazardous substance removing material capable of efficiently capturing and quickly inactivating hazardous substances of microbe origin such as viruses and bacteria, so as to minimize influences on the human body, such material being unlikely to be influenced by, for example, dimensional changes derived from dynamical and physical properties or a use environment (particularly humidity). The present invention provides a hazardous substance removing material which comprises a support having antibodies supported thereon, wherein a support is composed of a fiber which comprises at least one polymer having a carbonyl group and/or an ether group and has a volume swelling degree of not less than 1.1% to less than 10% in a water at 20° C.

Abstract: Water soluble polymers having formula I: Y-(L1)ni-(C(O))n2—(R1)n3—R2 are claimed. The polymers may contain multiple water soluble, immunogenicity reducing moieties and multiple active moieties. The polymers may be linked to a protein, or a peptide having up to twelve amino acids.

Abstract: A compound of the general formula X-[Q-W—(CH?CH)n—(CH2)2-L]m (I) in which X represents a polymer; Q represents a linking group; W represents an electron-withdrawing group; n represents 0 or an integer of from 1 to 4; L represents a leaving group; and m represent an integer of from 1 to 8. The compounds find use in the conjugation of biological molecules.

Abstract: The present invention relates to a seed-conjugated polymer support. In particular, the present invention is directed to a seed-conjugated polymer support for aggregating biomolecules, a method for preparing the same, and a method for removing ?-2-microglobulin.

Abstract: Disclosed are human relaxin-Fc fusion proteins having an increased serum half-life, polynucleotides encoding the same, and intermediates formed during the fusion protein biosynthesis. The fusion proteins may include a linker portion or other sections as well. Suitable fusion proteins are also those predicted to have the same effect as human relaxin in vivo, based, for example, on structural modeling. The fusion protein is useful in the treatment of a number of diseases and conditions, including heart disease, vascular disease, wound healing, fibrosis, fibromyalgia, and promoting angiogenesis.

Abstract: The invention relates to synthetic platelet compositions and methods useful in diminishing bleeding and blood loss. The synthetic platelets of the invention can comprise a biocompatible, biodegradable polymer, including, for example, a poly(lactic-co-glycolic acid)-poly-L-lysine (PLGA-PLL) block copolymer, having conjugated PEG arms terminating with RGD motif containing peptides. The invention further comprises compositions and methods useful in the delivery of therapeutic agents.

Abstract: The invention provides RGD-containing cyclic peptidomimetics; conjugates of said peptidomimetics and a moiety of a payload selected from fluorescent probes, photosensitizers, chelating agents, or cytotoxic agents; and pharmaceutical compositions comprising these conjugates. The conjugates of the invention are useful both for diagnostic purposes and treatment of various diseases, disorders and conditions. More specifically, conjugates comprising fluorescent probes can be used for diagnostic purposes, e.g., visualization of organs and tissues, and diagnosis of tumors; conjugates comprising photosensitizers can be used for photodynamic therapy of both tumors and nonneoplastic tissues; conjugates comprising chelating agents can be used in radio imaging or radiotherapy; and conjugates comprising cytotoxic agents can be used for in targeted chemotherapy.

Abstract: The present invention provides branched polymers which can be used as lubricants or shock absorbers in vivo. For example, the inventive polymers can be used as viscosupplements, viscoelastics, tissue space fillers, and/or anti-adhesive agents. Also provided are pharmaceutical compositions comprising the inventive polymers and methods of using them including, for example, in the treatment of arthritic and sport-injured knee joints; in reconstruction or cosmetic procedures, intervertebral disc repair, treatment of vocal cord problems, treatment of urinary incontinence, and prevention of adhesion formation following abdominal or gynecological surgery.

Abstract: The present invention relates to truncated IL-29 mutant molecules and methods of using same. The truncated IL-29 molecules can be used to treat viral infections, such as hepatitis C, autoimmune disorders and various types of cancer.

Abstract: A polynucleotide delivery vehicle comprising a modified polymer is provided herein, the modified polymer having the following formula: in which W1, W2, W3, W4, W5, W6, Z1, Z2, Z3, Z4, Z5, Z9, R1, R2, R3, R4, R5, n1, n2, n3, n4, n5, and n6 are defined herein. Also disclosed are methods of delivering a polynucleotide to the cytoplasm of a selected tissue type or cell type and methods of reducing expression of a gene in a cell or a subject in need thereof with the modified polymer.

Abstract: The present invention relates to Y-shape branched PEG derivatives of formulae (I) to (IV). The present invention also relates to conjugates of these Y-shape derivatives and drug molecules, pharmaceutical compositions comprising those conjugates.

Abstract: A composition includes at least one biologically active agent covalently attached to a first polymerizing molecule that is adapted to undergo a free radical polymerization. The first polymerizing molecule retains the ability to undergo free radical polymerization after attachment of the bioactive agent thereto. The first polymerizing molecule is preferably biocompatible. The polymerizing molecule can, for example. be dihydroxyphenyl-L-alanine (DOPA) or tyrosine. The composition can also include a second component synthesized by reacting at least one core molecule having a plurality of reactive hydrogen groups with at least one multi-isocyanate functional molecule to create a conjugate including terminal isocyanate groups. The conjugate molecule is reacted with a second polymerizing molecule that is adapted to undergo a free radical polymerization. The second polymerizing molecule includes a reactive hydrogen to react with the isocyanate groups of the conjugate.

Abstract: Disclosed herein are compositions comprising cross-linkers for cross-linking a retention vehicle polymer. The compositions are particularly useful for local administration of a bioactive agent, wherein prolonged or extended availability of the bioactive agent at the site of administration is desired. Also disclosed are methods of delivering the compositions to a subject.

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: An antibody-fragment-immobilizing substrate includes a substrate and at least one set of antibody fragments, wherein the antibody fragments of each set includes at least two types of separate antibody fragments that are capable of recognizing one type of antigen and that are independently immobilized on the substrate in a positional relationship that allows each of the antibody fragments in one set to bind to the same antigen.

Abstract: A non-enzymatically self cleaving dipeptide element is provided that can be linked to known medicinal agents via an amide bond. The dipeptide will spontaneously be cleaved from the medicinal agent under physiological conditions through a reaction driven by chemical instability. Accordingly, the dipeptide element provides a means of linking various compounds to known medicinal agents wherein the compounds are subsequently released from the medicinal agent after a predetermined time of exposure to physiological conditions. For example, the dipeptide can be linked to an active site of a drug to form a prodrug and/or the dipeptide may comprise a depot polymer to sequester an injectable composition comprising the complex at the point of administration.

Abstract: Compositions and methods of making a modified polyhydroxylated polymer comprising a polyhydroxylated polymer having reversibly modified hydroxyl groups, whereby the hydroxyl groups are modified by an acid-catalyzed reaction between a polydroxylated polymer and a reagent such as acetals, aldehydes, vinyl ethers and ketones such that the modified polyhydroxylated polymers become insoluble in water but freely soluble in common organic solvents allowing for the facile preparation of acid-sensitive materials. Materials made from these polymers can be made to degrade in a pH-dependent manner. Both hydrophobic and hydrophilic cargoes were successfully loaded into particles made from the present polymers using single and double emulsion techniques, respectively. Due to its ease of preparation, processability, pH-sensitivity, and biocompatibility, of the present modified polyhydroxylated polymers should find use in numerous drug delivery applications.

Abstract: There is provided a novel target recognition molecule. The target recognition molecule has a specific reactivity, and can be densely self-assembled and immobilized reversibly or irreversibly at a predetermined site in a microfluidic device. And The target recognition molecule including: (1) a target recognition peptide segment having an amino acid sequence which specifically interacts with a target substance capable of causing an immune reaction; and (2) an electrostatically-charged segment which is provided with three or more electrostatically-charged functional groups capable of being electrically charged to the same polarity in the same solution.

Abstract: Provided herein are polymeric ?-hydroxy aldehyde or ?-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the ?-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

Abstract: A dihydroxyphenyl cross-linked macromolecular network is provided that is useful in artificial tissue and tissue engineering applications, particularly to provide a synthetic macromolecular network for a wide variety of tissue types. In particular, artificial or synthetic cartilage, vocal cord material, vitreous material, soft tissue material and mitral valve material are described. In an embodiment, the network is composed of tyramine-substituted and cross-linked hyaluronan molecules, wherein cross-linking is achieved via peroxidase-mediated dityramine-linkages that can be performed in vivo. The dityramine bonds provide a stable, coherent hyaluronan-based hydrogel with desired physical properties.

Abstract: A method and article to immobilize a protein, including, for example, combining the protein and a mixture comprised of an activated spacer compound having a maleimide group in a buffer solution, to form a maleimide-modified protein; and contacting the maleimide-linker-modified protein and a buffer swollen, thiol-modified, surface bound polymer to immobilize the maleimide-linker-modified protein on the polymer surface of the article. Also disclosed are articles having an immobilized protein thereon, and to methods of using the articles having an immobilized protein, as defined herein.

Abstract: The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase (“hybrid”) approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to one of the fragments. The fragments are then coupled together in the solid solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to other fragments. The present invention is very useful for forming insulinotropic peptides such as GLP-1(7-36) and its natural and non-natural counterparts.

Abstract: A structured drug system that is useful for delivering a drug payload to a specific tissue or cell type is disclosed. The system is based on purified polymalic acid. This polymer isolated from natural sources is biocompatible, biodegradable and of very low toxicity. The polymer is extremely water soluble and contains a large number of free carboxyl groups which can used to attach a number of different active molecules. In the examples disclosed N-hydroxysuccinimide esters of the carboxyl groups are used to attach such molecules. The active molecules include monoclonal antibodies to promote specific cellular uptake and specific pro-drugs such as antisense nucleic acids designed to modify the cellular metabolism of a target cell. The pro-drugs are advantageously linked by a somewhat labile bond so that they will be released under specific conditions. In addition, the system contains amide-linked valine to encourage membrane disruption under lysosomal conditions.

Abstract: The invention provides CD-NP peptides that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the peptide not attached to the water soluble oligomer.

Abstract: The present invention relates to Y-shape branched PEG derivatives of formulae (I) to (IV). The present invention also relates to conjugates of these Y-shape derivatives and drug molecules, pharmaceutical compositions comprising those conjugates.

Abstract: Disclosed is a water-soluble high-molecular weight conjugate of physiologically active substances which enable medicament to release without depending on the enzymes in a living body and which is expected to have a useful therapeutic effect. A high-molecular weight conjugate of a physiologically active substance has a substituent group represented by a general formula (1) bonded to a side-chain carboxy group of a block copolymer which has a polyethylene glycol moiety and either a polyaspartic acid moiety or a polyglutamic acid moiety.

Abstract: Cationic polymers hydrolyzable to zwitterionic polymers, monomers for making the cationic polymers, surfaces that include the polymers, and methods for making and using the cationic polymers and surfaces. The cationic polymers include counterions and/or hydrolyzable groups that release active agents.

Abstract: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: A complex comprising at least one target protein and at least one binding molecule having a binding affinity for said target protein, wherein said molecule having a binding affinity is covalently or non-covalently bound to at least one water-soluble polymer

Abstract: A new method of preparing a tertiary alkyl ester of a polyalkylene oxide is provided. The new method employs milder conditions that avoid the back reaction to the starting polyalkylene oxide. The tertiary alkyl ester of a polyalkylene oxide is then reacted with a suitable acid to produce a polyalkylene oxide acid.

Abstract: Methods, compositions and articles of manufacture involving conformationally flexible conjugated polymers are provided. A structure is provided comprising the conformationally flexible conjugated polymer bound to or associated with at least one member of a binding pair comprising a sensor molecule and a target molecule or the complex they form. The conformationally flexible conjugated polymer comprises at least one angled linker having bonds to its two adjacent polymeric units which form an angle of less than about 155° with respect to one another. Methods of use of such structures and solutions comprising them are also provided.

Abstract: Amphiphilic copolymer, containing at least a hydrophilic chain segment (A) and a hydrophobic chain segment (B), wherein the hydrophilic chain segment (A) contains peptides and wherein the hydrophobic chain segment (B) contains acetal groups or orthoester groups. The hydrophilic chain segment (A) preferably contains glutamine/glutamic acid units or asparagines/aspartic acid units, making a biodegradable copolymer which can form a thermogel.

Abstract: Modified human apolipoprotein A-I polypeptides and uses thereof are provided.

Abstract: The present invention is directed to antibodies having specificity for a heavy chain class at the same time as having specificity for a first light chain. Such antibodies can be used in a method of detecting or monitoring a malignant plasma cell disease comprising determining in a sample the ratio between the relative amounts of immunoglobulins having: (i) a heavy chain class bound to ? light chains; and (ii) immunoglobulins having the same heavy chain class but bound to ? light chains.

Abstract: Modifying agents, e.g., a poly(sulfonyl) azide, are attached to a substrate surface, e.g., the surface of a polyolefin particle, by a process comprising the steps of: A. Contacting in an open contact zone and under a flow of inert gas a substrate with a modifying agent, binding agent, e.g., a phenolic-based antioxidant, and a liquid mixing agent, e.g., methylene chloride, to form a substrate mixture; B. Closing the contact zone and stopping the flow of inert gas to the contact zone; C. Agitating the substrate mixture under the inert gas in the closed contact zone to commence evaporation of the liquid mixing agent; D. Reducing the temperature and pressure of the closed contact zone while continuing to agitate the substrate mixture; and E. Completing the substantial evaporation of the mixing agent from the substrate mixture by opening the contact zone and initiating an inert gas flow while continuing agitation of the substrate mixture and maintaining a reduced pressure.

Abstract: Methods for preparing polymer-drug conjugates are provided. The disclosed methods involve polymeric reagents comprising a moiety of atoms arranged in a specific order, wherein the moiety is positioned between a water-soluble polymer and a reactive group. Related methods, compositions, preparations, and so forth are also provided.

Abstract: The invention provides peptides that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the peptide not attached to the water soluble oligomer.

Abstract: The invention provides protegrin that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention has enhanced half-life and/or reduced clearance.

Abstract: The invention provides peptides that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the peptide not attached to the water soluble oligomer.

Abstract: The invention provides peptides that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the peptide not attached to the water soluble oligomer.

Abstract: The invention provides osteocalcin that is chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the peptide not attached to the water-soluble oligomer.

Abstract: The invention provides peptides that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the peptide not attached to the water soluble oligomer.