Abstract: The present invention provides an anticoagulant agent including a first element capable of inhibiting coagulation and a second element capable of targeting an activated platelet wherein upon administration of the agent to a subject the second element directs the first element to the activated platelet. Also provided is a probe for detecting a blood vessel abnormality including (a) a binding element capable of targeting an activated platelet and (b) a label. Applicant has shown that agents and probes directed to activated platelets are useful in the diagnosis and therapy of coagulation disorders.

Abstract: The invention provides for preparing a polymer-active agent conjugate, the method comprising the steps of reacting an amino acid derivative with a biologically active agent under conditions to form a polymer-active agent conjugate.

Abstract: This invention pertains to methods for producing homogeneous recombinant proteins that contain polymer initiators at defined sites. The unnatural amino acid, 4-(2?-bromoisobutyramido)phenylalanine of formula 1, was designed and synthesized as a molecule comprising a functional group further comprising an initiator for an atom-transfer radical polymerization (‘ATRP”) that additionally would provide a stable linkage between the protein and growing polymer. We evolved a Methanococcus jannaschii (Mj) tyrosyl-tRNA synthetase/tRNACUA pair to genetically encode this unnatural amino acid in response to an amber codon. To demonstrate the utility of this functional amino acid, we produced Green Fluorescent Protein with the unnatural amino acid initiator of formula 1 site-specifically incorporated on its surface (GFP-1).

Abstract: Water soluble polymers having formula I: Y-(L1)n1-(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 method for improving the retention between the surfaces of medical devices. The method includes coating a surface of one medical device such as a stent with a coating that includes a functional group and coating a surface of another medical device such as a balloon with a coating that includes an identical or different functional group. The method further includes interacting the coated surfaces to produce a plurality of bonds between the surfaces, thereby improving retention.

Abstract: Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof.

Abstract: The present invention relates to water-soluble high-molecular-weight polymer drug carriers and their conjugates with drugs, derived from dendrimers of the amidoamine and 2,2-bis(hydroxymethyl)propanoic types, the amino and hydroxy end groups of which are attached to semitelechelic copolymers of N-(2 hydroxypropyl)methacrylamide (HPMA) through biodegradable spacers. The polymer carriers and conjugates enable targeted transport notably of anticancer drugs into solid tumors in which biodegradation, the associated controlled drug release and subsequent elimination of polymer carrier from the organism are provided. The polymer carrier conjugated with a cancerostatic for use in targeted therapy of human tumors.

Abstract: The present invention discloses latent thioester functionalities attached to the C-terminus of a first polypeptide, or a first fragment thereof having a Cys residue at its N-terminus, and a process using this functionality for the preparation of polypeptide thioesters, in particular of ubiquitin thioesters, this process comprising preparing a polypeptide or a fragment thereof, being attached to a latent thioester functionality, which can then be ligated with a second polypeptide fragment, followed by selective activation of the latent thioester functionality group, to provide the requested polypeptide thioester. There are also provided the polypeptides obtained by this method, specific unnatural amino acids useful to be incorporated within the polypeptide thioesters, and kits for preparing them.

Abstract: Provided is a method for immobilizing a macromolecule to a solid support material using poly(ethylene glycol), and a device obtained from the method. The macromolecule can be a polypeptide, such as an antibody.

Abstract: Disclosed are hydrogel compositions formed by the mixture of a tetramethylmethane substituted with one or more polyethylene glycols, and wherein each polyethylene glycol substituent is independently further substituted with one or more electrophilic groups, and a tetramethylmethane substituted with one or more polyethylene glycols, and wherein each polyethylene glycol substituent is independently further substituted with one or more nucleophilic groups. Disclosed are also methods of preparing the above hydrogels. The hydrogel compositions can further comprise pharmaceuticals, such as analgesics or local anesthetics. Disclosed are also methods of sealing a wound, preventing post-surgical adhesion, and reducing post-surgical pain using the disclosed hydrogels.

Abstract: A sensor system, and a method of detecting a target analyte, comprises a chemically functionalized block copolymer, and a target analyte. The block copolymer exhibits a color change in the visible spectrum upon exposure to the target analyte.

Abstract: Provided is a filler for affinity chromatography which is useful for protein purification and contains porous particles that have a high dynamic binding capacity for proteins and excellent pressure characteristics. The filler for affinity chromatography of the present invention is characterized in that it includes a porous particle consisting of a polymer of vinyl monomer including a cross-linkable vinyl monomer that contains hydroxyl group but does not contain epoxy group and an epoxy group-containing non-cross-linkable vinyl monomer, or a cross-linkable vinyl monomer that contains hydroxyl group and epoxy group, ligands bound to the porous particle, and ring-opened epoxy groups.

Abstract: Novel implantable tissue fixation methods and compositions are disclosed. Methods and compositions of tissue, fixed using polymeric and/or variable length crosslinks, and di- or polymercapto compounds are described. Also described are the methods and compositions wherein the tissue is fixed using biodegradable crosslinkers. Methods and compositions for making radio-opaque tissue are also described. Methods and compositions to obtain a degradable implantable tissue-synthetic biodegradable polymer composite are also described. Compositions and methods of incorporating substantially water-insoluble bioactive compounds in the implantable tissue are also disclosed. The use of membrane-like implantable tissue to make an implantable drug delivery patch are also disclosed. Also described are the compositions and methods to obtain a coated implantable tissue. Medical applications implantable tissue such as heart valve bioprosthesis, vascular grafts, meniscus implant, drug delivery patch are also disclosed.

Abstract: An object of the present invention is to provide a method of immobilizing the biologically active substance which has an excellent capability of immobilizing a target biologically active substance, and exhibits low nonspecific adsorption of the biologically active substance to provide a high S/N ratio, without using a functional group for fixing the biologically active substance and without having a process of inactivating the functional group for fixing the biologically active substance after immobilizing the biologically active substance. The above object is achieved by a method of immobilizing a biologically active substance comprising the step of: bringing a solution into contact with a compound-side surface of an immobilizing substrate to immobilize the biologically active substance on a surface of the immobilizing substrate, the solution being prepared by dissolving the biologically active substance in a phosphate buffer having a phosphate concentration of 0.

Abstract: The present invention is generally directed to a new class of TPEs made from peptide terminated low Tg polymers and methods for making them. The middle block of these TPE is a telechelic polymer with a Tg that is below the intended service temperature of the TPE. The terminal peptide segments of these TPEs are short (from about 1 to about 10 amino acids long) and tend to from sheet type secondary structures through intermolecular hydrogen bonds, creating physical crosslinks between polymer chains. The dissimilarity of the peptide hard component and the elastomeric soft component results in very strong segregation between the microphase domains and a low plastic deformation for the resulting TPE. And since the Tm of the crystalline peptide phase can be adjusted, these new TPEs may be tailored to fit the intended service temperature and are melt-processable.

Abstract: Disclosed are polyvalent macromolecules, compositions comprising the macromolecules, and methods of use. The polyvalent macromolecules have a polymer backbone and pendent groups attached to the polymer backbone. Some or all of the pendent groups have optionally a linker, a surface-seeking group capable of binding strongly to a metal surface, and a spectroscopically detectable chromophore detectable.

Abstract: Conjugates comprising a N-oxime bond are disclosed. In one embodiment, a suitable conjugate is represented by the following Formula (I): wherein R? is derived from a compound comprising at least one reactive amide group, R? is derived from a compound comprising at least one reactive aminooxy group, and X is H, CnH(n+2) or other atoms. Additional methods are also provided.

Abstract: Acoustically responsive particles and methods are provided for their use. Methods are provided for making and using tunable, monodisperse acoustically responsive particles and negative contrast acoustic particles, wherein the particles can contain a functional group available for covalent modification.

Abstract: The present invention relates to chromatography matrices including ligands based on one or more domains of immunoglobulin-binding proteins such as, Staphylococcus aureus Protein A (SpA), as well as methods of using the same.

Abstract: The present disclosure describes environmentally responsive polypeptides capable of displaying stimuli-triggered conformational changes in a reversible or irreversible manner that may be accompanied by aggregation. Polypeptides include a number of repeated motifs and may be elastomeric or non-elastomeric. The polypeptides may be used to deliver therapeutics to a biological site and to develop bioactive polypeptides that are environmentally responsive.

Abstract: The present invention is directed membrane active poly(vinyl ester) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cells in vivo. RNAi polynucleotides are conjugated to the poly(vinyl ester) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(vinyl ester) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.

Abstract: Copolymers, such as block copolymers, having at least one block that is a random copolymer of ?-caprolactone and ?-carboxy-?-caprolactone are described. Also described are methods of using such copolymers, such as, for example, in medical devices.

Abstract: The present invention is directed membrane active poly(acrylate) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides cells in vivo. RNAi polynucleotides are conjugated to the poly(acrylate) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(acrylate) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.

Abstract: Novel compounds of the general formula (I): in which X represents a polymer; Q represents a linking group; W represents an electron-withdrawing moiety or a moiety preparable by reduction of an electron-withdrawing moiety; each of R1 and R2 independently represents a hydrogen atom or a C1-4alkyl group; and either Z1 represents a protein or a peptide linked to CR2 via a nucleophilic moiety, and Z2 represents a molecule linked to CR2 via a nucleophilic moiety, or Z1 and Z2 together represent a single group derived from a protein or peptide linked to CR via two nucleophilic moieties.

Abstract: The present invention relates to processes for making synthetic polyisoprene latex and synthetic polyisoprene condoms. A process for making a compounded synthetic polyisoprene latex suitable for making a latex film comprises (a) compounding a synthetic polyisoprene latex with suitable compounding ingredients, (b) maturing the latex and optionally (c) storing the latex; characterized in that steps (a), (b) and (c) if included are carried out at a low temperature so as to minimize prevulcanization of the latex. Condoms can be made from latexes produced according to the process of the invention.

Abstract: Amide compounds are defined and are polymerized to create polyesters and polyurethanes having amide units bearing a pendant functional group, where the nitrogen atom of the amide group is part of the polymer backbone. The pendant functional group of the functionalized amide polymer may be modified or added by post polymerization functionalization of the functionalized amide polymer. The pendant functional group of the functionalized amide polymer may include a protecting group that may be removed after polymerization. The pendant functional groups of the functionalized amide polymers may be used to modulate the physical, chemical and biological properties of the polymers.

Abstract: A bio-adhesive supramacromolecular complex of the general formula: wherein R1 is independently selected from the group consisting of an alkane unsubstituted or substituted with alkoxy groups; R2 is independently selected from the group consisting of C1-6 alkyl; R3 and R4 are independently selected from the group consisting of optionally substituted aliphatic or aromatic alkyl; R5 is independently selected from the group consisting of H or C1-6 alkyl; W is a hydrogen-bond accepting functional group-containing entity; Y is a carboxylic acid ester or amide linkage; R is an independently selected peptide linking group; T1, T2, T3 and T4 are independently selected polymer residues; and m1, m2, m3, n1 and n2 are integers selected from at least 25; and wherein P has a molecular weight of about 1×103 to 1×107 and Q has a molecular weight of about 1×103 to 1×107. The complex provides controlled nitric oxide release over a longer period of time than prior art compounds in the locally delivery systems.

Abstract: One-part binder compositions are described that may include a protein and a crosslinking combination. The crosslinking combination may include at least a first crosslinking compound and a second crosslinking compound. The first and second crosslinking compounds are individually crosslinkable with each other and with the protein. Examples of the protein include soy protein. Fiber products and methods of making the fiber products are also described. The fiber products may include organic fibers, inorganic fibers, or both, in a cured thermoset binder based on solutions of the one-part binder compositions.

Abstract: The present invention provides poly(amide) polymers, polyconjugates, compositions and methods for the delivery of oligonucleotides for therapeutic purposes.

Abstract: Biodegradable, cross-linked polymer particle embolics and methods of making the same are described. The particle embolics can be used as embolization agents.

Abstract: The present invention relates to compositions for the treatment of cancerous tissues in warm-blooded animals containing one or two anticancer agents attached to polymeric carriers having monomer units derived from one or more of N-(2-carboxypropyl)methacrylamide (2-CPMA), N-(3-carboxypropyl)methacrylamide (3-CPMA), N-(2-aminopropyl)methacrylamide (2-APMA) and/or N-(3-aminopropyl)methacrylamide (3-APMA) are also included. Anticancer agents in compositions can be attached to said polymeric carrier by side-chains which can be susceptible to hydrolysis by lysosomal enzymes intracellularly. Compositions can also include a targeting ligand attached to the polymeric carrier, optionally through a second linker.

Abstract: As a substance used as a contrast agent for a method of nuclear magnetic resonance analysis or a method of magnetic resonance imaging, a substance with high selectivity and high sensitivity was demanded. According to the present invention, when a polymer having, in a side chain thereof, a sequence of a 1H—13C—15N, 1H—15N—13C or 1H—13C—13C bond, that is, a structure labeled with stable isotopes of 13C and 15N, is used, the abundance of such a sequence in one molecule can be increased, and hence, high selectivity and higher sensitivity can be attained when used as a contrast agent.

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: Auristatin compounds and conjugates thereof are provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -LD-D, the protein based recognition-molecule being connected to the polymeric carrier by LP. Each occurrence of D is independently an Auristatin compound. LD and LP are linkers connecting the therapeutic agent and PBRM to the polymeric carrier respectively. Also disclosed are polymeric scaffolds useful for conjugating with a PBRM to form a polymer-drug-PBRM conjugate described herein, compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions.

Abstract: Elastogenic nanoparticles including a polymeric core having a surface that is functionalized with a cationic amphiphilic compound, and comprising an active agent having pro-elastogenic and/or anti-proteolytic activity, are described herein. The elastogenic nanoparticles can be used in method of stimulating elastogenesis in a subject by administering to the subject a therapeutically effective amount of elastogenic nanoparticles.

Abstract: The present disclosure relates to compounds and medical devices activated with a solvophobic material functionalized with a first reactive member and methods of making such compounds and devices.

Abstract: This invention discloses the creation of a novel single ligand-targeted multi-stereoisomer peptide-polymer conjugate compounds comprising a group of different synthetic and chemically modified stereoisomer peptides that have been conjugated to a biocompatible polymer carrying a peptide ligand for targeted delivery and/or encapsulated in ligand targeted polymer nanoparticles. The unique physicochemical properties of the stereoisomer peptides provide therapeutic compounds with ideal biopharmaceutical properties. The stereoisomer peptides carried by the polymer are delivered to cells or tissues to inhibit, suppress, block, antagonize or disrupt, simultaneously and independently, the functional domain of different disease causing proteins.

Abstract: The present invention relates to polymeric reagents and conjugates thereof, methods for synthesizing the polymeric reagents and conjugates, pharmaceutical compositions comprising the conjugates and methods of using the polymer conjugates including therapeutic methods where conjugates are administered to patients.

Abstract: A method is provided for the preparation of a poly(amic acid) in which ring opening polymerization is employed to react the monomers ethylenediaminetetraacetic dianhydride and paraphenylenediamine in an aprotic solvent. The resulting poly(amic acid) composition is suitable as a biocompatible material, such as a biomedical implant, implant coating material, tissue scaffold material, controlled release drug delivery vehicle, and cellular growth substrate.

Abstract: Conjugates comprising a N-oxime bond are disclosed. In one embodiment, a suitable conjugate is represented by the following Formula (I): wherein R? is derived from a compound comprising at least one reactive amide group, R? is derived from a compound comprising at least one reactive aminooxy group, and X is H, CnH(n+2) or other atoms. Additional methods are also provided.

Abstract: A method for producing a polypeptide, includes at least one native ligation step using a peptide functionalized with a selenium group. The selenium peptides and compounds are also described.

Abstract: Identification and use of proteins fluorescently labeled and that undergo a change in fluorescence index upon binding bilirubin are described. Probes are disclosed which are labeled at a cysteine or lysine residue and also probes labeled at both cysteine and lysine with two different fluorophores. These probes are useful for determination of unbound bilirubin levels in a fluid sample.

Abstract: A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -LD-D, the protein based recognition-molecule being connected to the polymeric carrier by LP. Each occurrence of D is independently a therapeutic agent having a molecular weight ?5 kDa. LD and LP are linkers connecting the therapeutic agent and PBRM to the polymeric carrier respectively. Also disclosed are polymeric scaffolds useful for conjugating with a PBRM to form a polymer-drug-PBRM conjugate described herein, compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions.

Abstract: A method of supplementing a diet and ameliorating oxidative stress in a mammal includes administering a pharmaceutically effective amount of an active compound having the chemical structure: where n=1-4 and X is selected from the group consisting of hydrogen, lithium sodium, potassium, rubidium, cesium and francium.

Abstract: A peptide cross-linking agent in the form of a linear molecule has a molecular mass of 3 to approximately 60 kDa. The peptide cross-linking agents are used for cross-linking functionalized polymers to form hydrogels having two or more components.

Abstract: Biomimetic adhesive compositions can be used in various aspects of subterranean treatment operations. Methods for treating a subterranean formation can comprise: providing an adhesive composition that comprises a first polymer comprising a plurality of monomers that comprise a phenolic moiety, a biopolymer that is crosslinkable with the first polymer, a crosslinking agent, and an oxidizing agent; introducing the adhesive composition into a subterranean formation; and forming a coacervate-bound surface in the subterranean formation by crosslinking the first polymer.

Abstract: Ligand functionalized substrates, methods of making ligand functionalized substrates, and methods of using functionalized substrates are disclosed.

Abstract: One-part binder compositions are described that may include a protein and a crosslinking combination. The crosslinking combination may include at least a first crosslinking compound and a second crosslinking compound. The first and second crosslinking compounds are individually crosslinkable with each other and with the protein. Examples of the protein include soy protein. Fiber products and methods of making the fiber products are also described. The fiber products may include organic fibers, inorganic fibers, or both, in a cured thermoset binder based on solutions of the one-part binder compositions.

Abstract: Carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a boronic acid, configured to present the polymer containing a boronic acid to an environment external to the nanoparticle and related compositions, methods and systems.

Abstract: The present invention relates to functionalized ploy(2-oxazoline) polymers, which are very suitable as a carrier and/or delivery vehicle (conjugate) of drugs, such as small therapeutic molecules and bio-pharmaceuticals. These polymers are characterized in that they comprise repeating units that are represented by the following formula —[N(R1)—(CHR2)m]- wherein R1 is R3—(CHR4)n-CONH—R5; R2 is selected from H and optionally substituted C1-5alkyl; R3 is CH2CO, C(O)O, C(O)NH OR C(S)NH; R4 is selected from H and optionally substituted C1-5alkyl; R5 is H; an C1-5alkyl; aryl; or a moiety comprising a functional group that can be used for conjugation; m is 2 or 3 and n is 1-5; or n is 0 and R3 is CH2. The invention relates further to a conjugate of these polyoxazoline polymers with at least one active moiety, such as a therapeutic moiety, a targeting moiety and/or diagnostic moiety, and to the use of these conjugates in the therapeutic treatment or prophylactic treatment or diagnosis of a disease or disorder.