Abstract: A biologically active complex of lactoferrin with a branched non-peptide hydrophilic polymer, one example of which is represented by the following formula [I]: LF-[X-Lp-R—(Yp-POLY)q]n ??[I] Wherein LF is lactoferrin, X is a linkage generated by reaction of functional groups, L is a linker, R is an aliphatic hydrocarbon group having at least 3 carbon atoms, Y is a heteroatom linkage, POLY is a non-peptide hydrophilic polymer, p is 0 or 1, q is an integer of 2 to 10, and n is an integer of 1 to 10.

Abstract: The present invention provides for IL-17 receptor like polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, agonists and antagonists (including selective binding agents), and methods for producing IL-17 receptor like polypeptides. Also provided for are methods for treatment, diagnosis, amelioration, or prevention of diseases with IL-17 receptor like polypeptides.

Abstract: Protein formulations containing a poloxamer as a surfactant, and methods for maintaining the biological activity in protein formulations without adding an antioxidant and for inhibiting the formation of foreign insoluble matters by adding a poloxamer as a surfactant.

Abstract: This invention relates to a method of producing a modified (poly)peptide, said method comprising the step of modifying in an organic solvent a crown ether-bound (poly)peptide at one or more carboxylic groups by esterification or thioesterification and/or at the amino group of the N-terminal amino acid by amidation or alkylation. Furthermore provided are (poly)peptides and antibodies obtainable with the method of the invention as well as medical uses thereof.

Abstract: Disclosed herein are an N-terminal modified PEG-TRAIL conjugate and a preparation method and use thereof. The PEG-TAIL conjugate has pharmaceutical activity identical or similar to that of native TRAIL (TNF-related apoptosis-inducing ligand) with extended in vivo half-life and enhanced stability. Compared to native TRAIL, the PEG-TAIL conjugate exhibits high solubility and solution stability, with highly improved pharmacokinetic profiles. Thus, the PEG-TAIL conjugate may be very useful for preventing and treating proliferative diseases and autoimmune diseases.

Abstract: The present invention provides a means for increasing the serum half-life of a selected biologically active agent by utilizing transthyretin (TTR) as a fusion partner with a biologically active agent. Specifically, the present invention provides substantially homogenous preparations of TTR (or a TTR variant)-biologically active agent fusions and PEG-TTR (PEG-TTR variant)-biologically active agent fusions. As compared to the biologically active agent alone, the TTR-biologically active agent fusion and/or PEG-TTR-biologically active agent fusion has substantially increased serum half-life.

Abstract: The present invention provides a newly identified B7 receptor, zB7R1 that functions as lymphocyte inhibitory receptor, which is a PD-1-like molecule and is expressed on T cells. The present invention also provides the discovery of zB7R1's ability to bind to CD155. Methods and compositions for modulating zB7R1-mediated negative signaling and interfering with the interaction of its counter-receptor for therapeutic, diagnostic and research purposes are also provided.

Abstract: Interleuekin-1 receptor antagonists (IL-1Ra) including fusion proteins having a trimerizing domain and an IL-1Ra polypeptide sequence. The fusion proteins are part of trimeric complexes that are used in pharmaceutical compositions for treating diseases mediated by IL-1. Effective treatment of inflammatory diseases, such as rheumatoid arthritis and diabetes, are described.

Abstract: The invention is based on the discovery that certain biarsenical molecules react with specified target sequences, thereby providing a facile means for labeling polypeptides containing the target sequence. The invention is useful in creating stable mammalian cell lines expressing a certain tetracysteine tagged polypeptides, thereby overcoming toxicity associated with native tetracysteine. In addition, the invention allows for orthogonal labeling of polypeptides, thereby allowing for the observation of protein-protein interactions and conformational changes in proteins, for example.

Abstract: Protein and polypeptide derivatives and their salts are claimed characterized in that a protein or polypeptide is conjugated via an intermediate grouping containing at least one radical of the formula —C(R)?N— (or —N?C(R)—) or —CH(R)—NH— (or —NH—CH(R)—), wherein R is hydrogen or a hydrocarbon residue which may be substituted, with the same or a different protein or polypeptide, with a reporter group or a cytotoxic agent as well as a process for their preparation and the novel intermediates therefor.

Abstract: The present invention provide compounds, and pharmaceutical compositions thereof, encompassed by the formulae (I), (II) or (III). The present invention also provides methods for treating an FAAH mediated disease, disorder or condition by administering a therapeutically effective amount of a provided compound of the formulae (I), (II) or (III), or a pharmaceutical composition thereof, to a patient in need thereof. Additionally, the present invention provides methods for inhibiting FAAH in a patient by administering a therapeutically effective amount of a compound of the formulae (I), (II) or (III), or a pharmaceutical composition thereof, to a patient in need thereof.

Abstract: The invention provides novel compounds of formula (I), (II), (III), and (IV). The invention also provides pharmaceutical compositions comprising such compounds as well as methods for treating diseases associated with opioid receptor function by administering such compounds to an animal in need of treatment. The invention also provides therapeutic methods for the use of compounds of formula (V), as well as methods for treating diseases by administering such compounds.

Abstract: The present invention provides a crosslinking agent which have photodegradable protective groups at two ends to crosslink double-stranded nucleic acid, a nucleic acid and a protein or a polypeptide, or proteins or polypeptides, in particular, double-stranded RNA; a method for crosslinking a double-stranded RNA or the like using the same; a method for regulating gene expression, which can control the expression of a target gene at an arbitrary timing and location; and a method for examining a gene function. According to the present invention, crosslinking between double-stranded nucleic acids between a nucleic acid and a protein or a polypeptide, or between proteins or polypeptides, in particular, between double-stranded RNA can be easily formed, and in addition, the crosslinking can also be easily removed, so that the expression of a target gene can be easily controlled at an arbitrary timing and location with high efficiency.

Abstract: The present invention provides a method for refolding protein produced, for example, by Escherichia coli, that is inactive due to an as yet unformed higher order structure, or protein deactivated due to a change in conformation for some reason. The invention comprises a method, refolding kit, refolding agent, and molding that activate a native function or activity inherent to a protein through treatment with zeolite beta of protein produced, for example, by Escherichia coli, that is inactive due to an as yet unformed higher order structure, or protein deactivated due to a change in conformation for some reason. The invention also comprises a method for producing an active protein that utilizes the same. As compared with conventional methods, the present invention can provide a novel method for activating protein function that is highly versatile and generalizable, that employs a simple and easy protocol, and that is inexpensive and enables repeated use of the function activator.

Abstract: Dibenzofuran-4,6-dicarboxylic acid core structures having an aromatic substituent appended onto the at the C1 position using three different types of linkages are disclosed herein and shown to afford exceptional amyloidogenesis inhibitors that display increased affinity and greatly increased binding selectivity to TTR over all the other plasma proteins, relative to lead compound 1. It is further disclosed herein that these compounds function by imposing kinetic stabilization on the TTR tetramer.

Abstract: The invention relates to a carrier-drug conjugate comprising a carrier containing a polypeptide sequence having one or several cysteine radicals and a pharmacon containing a pharmaceutical and/or diagnostic active substance, a spacer molecule and a thiol binding group, whereby over 0.7 mol pharmacon per mol of cysteine radical is bound to the carrier by the thiol binding group. The invention also relates to a method for the production of said conjugate and to medicaments and diagnostic kits containing said conjugate.

Abstract: In part, the present invention relates to a compound or polymer comprising a non-protein-binding moiety and at least one protein-binding group. The present invention relates to a method of screening compounds or polymers for the property of inhibiting protein aggregation in solution, a method of preparing a compound or polymer having the property of protein aggregation inhibition in solution, a method of classifying a compound or polymer as either inhibitory of protein aggregation in solution or not inhibitory of protein aggregation in solution, and to a method of determining the preferential binding coefficient, ?XP, of an additive in a protein solution. The present invention also relates to a method of suppressing or preventing aggregation of a protein in solution, a method of decreasing the toxicological risk associated with administering a protein to a mammal in need thereof, and a method of facilitating native folding of a recombinant protein in solution.

Abstract: This invention relates to a process for purifying a polypeptide, a capture tag useful for purifying a polypeptide and a periodate-cleavable amino acid derivative useful for purifying a polypeptide. The polypeptide to be purified comprises a vicinal-amino-thiol, vicinal-amino-hydoxyl, vicinal-diol or vicinal-diamino group. The purification process comprises attaching the polypeptide to a purification matrix by contacting the polypeptide with a purification matrix comprising aldehyde or ketone groups under conditions which favor formation of a heterocyclic ring system, washing the purification matrix, and releasing the polypeptide from the purification matrix.

Abstract: The invention concerns a method for binding, in solution, at least a peptide composition and at least a lipophilic vector bearing an aldehyde function, the coupling comprising a step which consists in producing a hydrazone bond between the peptide compound and the lipophilic vector. The invention also concerns lipophilic vectors for use in this method, lipopeptides obtained by this method, uses of the lipopeptides for cell screening, and the applications of the invention, in particular for preparing targeting of an active principle of the peptide kind (for example hormone or neuropeptide) through physiological barriers such as cell membranes.

Abstract: Disclosed are methods of inactivating a protein, such as cleaving a disulfide bond of a protein, that involve contacting the protein with a reducing agent, a denaturant, and a hydroxide ion, wherein the pH of the composition is about 10.0 to about 14.0. Also disclosed are methods of treating or preventing a disease in a subject, such as a toxin-related disease or a prion-related disease, that involve contacting a subject with a pharmaceutically effective amount of a reducing agent, a denaturant, and a hydroxide ion, wherein the pH of the composition is about 9.0 to about 14.0. Also disclosed are compositions that include a reducing agent, a denaturant, and a hydroxide ion, wherein the pH of the composition is about 9.0 to about 14.0.

Abstract: The expression vectors and methods using an E. Coli expression system for the large scale production of IL-29 are described. The vectors utilize the IL-29 coding sequence with specific changes in nucleotides in order to optimize codons and mRNA secondary structure for translation in E. coli. Also included are methods of producing, purifying and pegylating an IL-29 polypeptide.

Abstract: The invention relates to a method which is used to efficiently mark proteins with the help of a micromixer, in addition to a device which enables said inventive method to be carried out in an economical manner and with additional auxiliary agents.

Abstract: The present invention provides a compound having a formula: where R1 is selected from the group consisting of alkyl, —CH2(OC2H4)OCH3, and —(OC2H4)OCH3; n is 0-4; Olig is an oligomer having a formula: -L-O-PAGR2]q where L is a optional linker moiety selected from the group consisting of —CH2O—, —CH2OX—, —OX—, —C(O)—, —C(O)X, —NH—, —NHC(O)—, —XNHC(O)—, —NHC(O)X—, —C(O)NH—, —C(O)NHX—, and where X is alkyl1-6 or is not present, Y is N or O or is not present, and R3 is alkyl1-6; PAG is a linear or branched polyalkylene glycol moiety; R2 is an alkyl1-22 capping moiety if X is present or alkyl2-22 if X is not present; and q is a number from 1 to the maximum number of branches on PAG; and m is 1-5.

Abstract: A method for the preparation of an allylic sulfide comprises contacting an activated sulfenyl compound of Formula (I) with a thiol of Formula (II) for a period of time sufficient to form an intermediate of Formula (III), and contacting the intermediate of Formula (III) with a thiophilic agent, in a polar solvent, to induce a [2,3]-sigmatropic rearrangement therein and thereby form an allylic sulfide of Formula (IV), with concomitant loss of a sulfur atom to the thiophilic agent, wherein in Formulas (I, II, II, and IV), X is S or SO2; Y is an aryl group, a substituted-aryl group, a heteroaryl group , or a substituted heteroaryl group; R1, R2, R3, R4, and R5 are each independently H, a hydrocarbon moiety or a substituted hydrocarbon moiety; and R is an organic moiety.

Abstract: A novel method of conjugating chelators to biomolecules such as proteins is provided. More particularly, the invention provides compositions and methods of using those compositions for the detection, purification and transport of divalent metal cation binding biomolecules.

Abstract: Peptides have been identified that bind with high affinity to hair, skin, and nails. Peptide-based hair conditioners, hair colorants, skin conditioners, skin colorants, and nail colorants are described. The peptide-based hair conditioners and hair colorants consist of a hair-binding peptide coupled to a hair conditioning agent or a coloring agent, respectively. The peptide-based skin conditioners and skin colorants consist of a skin-binding peptide coupled to a skin conditioning agent or a colorant, respectively. The peptide-based nail colorants consist of a nail-binding peptide coupled to a coloring agent. In all these compositions, the peptide may be directly coupled to the active agent or the coupling may be via a spacer. Personal care compositions containing these peptide-based conditioners and colorants are also described.

Abstract: Derivatives and conjugates of indinavir for generation of antibodies and labeled conjugates for use for detection of indinavir in biological samples. The derivatives are synthesized out of the indane ring hydroxyl group or the pyridine ring nitrogen of indinavir. Also disclosed is synthesis of a major metabolite of indinavir (M6) in a single step from indinavir using palladium catalyst and hydrogen gas. Indinavir M6 has been extended to synthesize various analogs of indinavir with suitable functional groups. These derivatives are useful in the development of indinavir immunogens, antibodies, and labeled conjugates in the development of indinavir immunoassays.

Abstract: The present invention relates to compounds and methods for synthesizing compounds wherein the compounds exhibit extended circulating half-life in the blood. The increase in circulating half-life is achieved by conjugating polypeptides to binding groups that exhibit high affinity for human serum albumin.

Abstract: This invention relates to a process for preparing a hapten-protein-polysaccharide conjugate and a hapten-protein conjugate by reacting a protein with a hapten to produce a hapten-protein conjugate, followed by reacting the hapten-protein conjugate with a polysaccharide to provide a conjugate mixture including the hapten-protein conjugate and a hapten-protein-polysaccharide conjugate. This invention also includes the process described above with the addition of a pharmaceutically acceptable medium or delivery vehicle into the conjugate mixture. The invention further includes the process described above where the hapten is luteinizing hormone releasing hormone peptides derived from E coil, or malaria derived peptides.

Abstract: A hedgehog conjugate which is characterized in that it contains: a) a polypeptide composed of 10 to 30 hydrophobic amino acids and/or amino acids which form transmembrane helices and are positively charged, b) 1 to 4 aliphatic, saturated or unsaturated hydrocarbon residues with a chain length of 10 to 24 C atoms and with a hydrophobic action or c) a hydrophobic thio compound covalently bound to a hedgehog protein and which has a several-fold increased activity and is suitable as a pharmaceutical agent.

Abstract: A molecule with two pendant phenylarsine moieties according to the general structural Formula (I) and tautomers, acids, and salts thereof: wherein: (i) R1 or R2, are each independently O?, S?, OR3 or SR3 with the provision that if either R1 or R2 is absent, the other remaining group is ?O or ?S; or R1 and R2, together with the arsenic atom, form a ring according to one of the general structural Formulae (II), (III), (IV), or (V): wherein R3 is H, CH(OH)CH2OH, or (CH2)q—Y, with q being 1–4 and Y being H, OH, NH2, SH, COOH, OAc, CONH2 or CN, and Z represents a hydrocarbon chain comprising 2–4 singly or doubly bonded carbon atoms each of which may be further substituted with one or more of hydrogen, methyl, ethyl, 1-propyl, 2-propyl, methoxy, hydroxy, amino, carboxy, sulfo, oxo, thio, halo (fluoro, chloro, bromo, or fluoro) and (CH2)n?SO3, wherein n? is 1 or 2; (ii) R4, R5, R6 and R7 are each independently H, F, OR3, R3, OAc, NH2, N(C1–C4 alkyl)2, R1; or R4 with R5, or R6 together with R7, or both, form

Abstract: The present invention relates to bio-molecule resistant surfaces for use in assays, particularly in assay devices such as arrays and microfluidic devices. The biomolecule resistant surface of the present invention are prepared by coating a substrate with hydrophilic terminated alkoxysilanes having formula (A): wherein R is an alkyl group of a size that allows for sufficient hydrolysis and n is 1, 2 or 3; R1 is a hydrophilic moiety; LC is a C1 to a C10 linker chain consisting of a group selected from alkyl, aryl, alkaryl and aralkyl and m is 1, 2, or 3; R2 is a C1 to a C7 alkyl group and x is 0, 1, or 2; and m+n+x is equal to 4.

Abstract: Protein and polypeptid derivatives and their salts are claimed characterized in that a protein or polypeptide is conjugated via an intermediate grouping containing at least one radical of the formula —C(R)?N— (or —N?C(R)—) or —CH(R)—NH— (or —NH—CH(R)—), wherein R is hydrogen or a hydrocarbon residue which may be substituted, with the same or a different protein or polypeptide, with a reporter group or a cytotoxic agent as well as a process for their preparation and the novel intermediates therefor.

Abstract: The present invention relates to methods and compositions for modifying peptides, polypeptides and proteins with polymers, especially glyco-mimetic polymers, so as to improve their biological activity or pharmacokinetic properties. The invention further provides methods and uses for such polymer-modified peptides, polypeptides and proteins. The invention is particularly suitable for use in the synthesis of polymer-modified synthetic bioactive proteins (FIG. 1D), and of pharmaceutical compositions that contain such proteins.

Abstract: A fibrin/fibrinogen binding conjugate for forming a depot for the sustained release of a pharmaceutically active substance from a fibrin clot. The conjugate comprises a fibrin/fibrinogen binding moiety bound to a pharmaceutically active substance either directly or via an intervening substance capturing moiety such as an antibody. The conjugate can also be a recombinant fusion protein comprising a fibrin/fibrinogen binding moiety such as VEGF165 C-terminal domain fused to a wound-healing substance such as leptin.

Abstract: This invention relates generally to the field of cell culture. More particularly, the invention relates to improving viability of recombinant cell cultures and the yields of secreted polypeptides therefrom by the addition of betaine to the tissue culture medium.

Abstract: The present invention relates to a folding process for the preparation of biologically active, dimeric, TGF-? (Transforming Growth Factor type ?)-like protein in a detergent-free folding buffer.

Abstract: A method for selective labeling of phosphate groups in natural and synthetic oligomers and polymers in the presence of chemically related groups such as carboxylic acid groups. The method is specifically applicable to biological oligomers and polymers, including phosphopeptides, phosphoproteins and phospholipids. In a specific embodiment, selective labeling of phosphate groups in proteins and peptides, for example, facilitates separation, isolation and detection of phosphoproteins and phosphopeptides in complex mixtures of proteins. Selective labeling can be employed to selectively introduce phosphate labels at phosphate groups in an oligomer or polymer, e.g., in a peptide or protein. Detection of the presence of the label, is used to detect the presence of the phosphate group in the oligomer or polymer. The method is useful for the detection of phosphoproteins or phosphopeptides.

Abstract: A method for producing a derivatized aldehydic support matrix material includes activating surface hydroxyl groups on the support matrix material and reacting the activated hydroxyl groups with an aldehydic alkoxy silane. The derivatized aldehydic support matrix material produced is useful for immobilizing bio-molecules in biological applications.

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: 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: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.

Abstract: Networks, hydrogels, and methods for networks and hydrogels comprising proteinaceous material consisting essentially of water soluble proteins and covalent interprotein crosslinks other than disulfide crosslinks.

Abstract: A homogeneous conjugate for targeting and treating diseased cells wherein the conjugate comprises an anti-cancer drug and a targeting protein, wherein said anti-cancer drug is selected from the group consisting of heat sensitizers, photosensitizers and apoptosis inducing compounds, a method for making such a conjugate, and methods for using the conjugate. The targeting protein is preferably transferrin.

Abstract: Methods for producing biocompatible heterogeneous proteinaceous networks crosslinked with a heterogeneous crosslinking agent, and novel heterogeneous crosslinked networks. Preferred heterogeneous crosslinking agents are silicone-based.

Abstract: The present invention provides methods for preparing, and compositions comprising, stabilized protein-polymer conjugates. More particularly, the present invention relates to the stabilization of individual and complexed subunits of multisubunit protein complexes by conjugation to polymers. Such conjugation acts to stabilize the specific subunit complexes in their native conformation in liquid medium.

Abstract: The present invention provides a conjugate wherein GP (glycoprotein) Ib and a lipid are bonded via polyalkylene oxide. The present invention also provides a complex (GPIb lipid complex) containing this conjugate and a free lipid. The GPIb lipid complex is expected to have a potential for practical application in a wide range, as a platelet substitute, a pharmaceutical agent for the prophylaxis or treatment of angiopathy, vascular damage and thrombosis, a diagnostic for vWF deficiency and the like, a biological or medical reagent, a reagent for screening platelet aggregation suppressant or antithrombosis, and the like. The GPIb lipid complex of the present invention is also useful as a diagnostic for finding the location of vascular lesion or thrombus formation, or a therapeutic agent thereof. Moreover, the GPIb lipid complex of the present invention is also superior in retention property in blood, which enables continuous expression of a pharmacological action.

Abstract: The invention relates to novel collagen peptides that are modified by grafting free or substitued thiol functions carried by mercaptoamine radicals. The aim of the invention is to provide thiol collagens that can be cross-linked in a sufficient and controlled manner by forming S—S bridges and which are biocompatible. This is achieved by means of the inventive thiol collagens which are characterized in that the mercaptoamine radicals are identical to or different from each other and are exclusively grafted on the aspartic and glutamic acids of the collagen chain by amide bonds. The invention also relates to a method for the production of said thiol and cross-linkable collagens. The novel modified cross-linkable and/or cross-linked collagens can be used as biomaterials.

Abstract: Methods for producing biocompatible heterogeneous proteinaceous networks crosslinked with a heterogeneous crosslinking agent, and the novel crosslinked networks.

Abstract: A non-polydispersed mixture of conjugates in which each conjugate in the mixture comprises a drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may result in less inter-subject variability than polydispersed mixtures of similar conjugates.