Abstract: The invention relates to active fragments of the IL-18 binding protein, to pharmaceutical compositions comprising such active fragments, and to medical uses thereof.

Abstract: The present invention provides ILT-2 variants having the property of binding to a given Class IpMHC with a KD of less than or equal to 1 ?M and/or an off-rate (Koff) of 2 S?1 or slower AND said polypeptide has at least a 45% identity and/or 55% similarity to SEQ ID NO: 19 AND said polypeptide inhibits CD8 binding to the given pMHC to a greater extent than the polypeptide SEQ ID NO: 3, CHARACTERISED IN THAT said polypeptide comprises an amino acid sequence selected from one of SEQ ID NOs 6 to 69. Such polypeptides are useful, either alone or associated with a therapeutic agent, for the inhibition of cyto-toxic T cell (CTL) responses.

Abstract: This invention relates to the delivery of agents to the body. One particular class of such agents are contrast agents useful in medical imaging techniques. The agents may be metals useful as contrast agents in magnetic resonance imaging (MRI), or in nuclear imaging, including positron emission tomography (PET), or as therapeutic agents in radiotherapy. The agents may alternatively be contrast agents useful in X-ray imaging. The invention also relates to methods by which agents for delivery to the body can be coupled to carriers and to targeting moieties effective to direct the agent to a specific locus within the body.

Abstract: There is provided a method of conjugating a polymer containing a free aldehyde group with a flavonoid in the presence of an acid catalyst, such that the polymer is conjugated to the C6 or C8 position of the flavonoid A ring. The resulting conjugates may be used to form delivery vehicles to deliver high doses of flavonoids, and may also be used as delivery vehicles to deliver an additional bioactive agent.

Abstract: Aspects of the present invention are directed to novel methods for making discrete polyethylene compounds selectively and specifically to a predetermined number of ethylene oxide units. Methods which can be used to build up larger dPEG compounds (a) containing a wider range of utility to make useful homo- and heterofunctional and branched species, and (b) under reaction configurations and conditions that are milder, more efficient, more diverse in terms of incorporating useful functionality, more controllable, and more versatile then any conventional method reported in the art to date. In addition, the embodiments of the invention allow for processes that allow for significantly improving the ability to purify the intermediates or final product mixtures, making these methods useful for commerial manufacturing dPEGs. Protecting groups and functional groups can be designed to make purification at large scale a practical reality.

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 present invention relates to biosensors. In some embodiments, the biosensors are modified ligand binding molecules. In some embodiments, the modified ligand binding molecule is a phosphate binding protein (PBP). In some embodiments, the modified ligand binding molecules are labeled to be capable of RET, e.g., comprising a donor and acceptor moiety. In some embodiments of the invention, there is a detectable change in RET (e.g., FRET) when the modified ligand binding molecule binds and/or releases the ligand (e.g., phosphate). The invention also provides related methods, reactions and assays.

Abstract: The invention relates chemical compound entry inhibitors and methods of determining such inhibitors that interact with regions of viruses, such as the dengue virus, as candidates for in vivo anti-viral compounds.

Abstract: Engineered proteins are used in the assembly of two-dimensional and three-dimensional nanostructure assemblies, based on systematic design and production of protein node structures that can be interconnected, for example, with streptavidin or streptavidin-incorporating struts to produce structures with defined dimensions and geometry. Nanostructure assemblies having utility as functional devices or as resists for the patterning of substrates have architectures including polygons, polyhedra, two-dimensional lattices, and three-dimensional lattices.

Abstract: The present invention relates to delayed release oral formulations comprising active ingredients and modified proteins used as excipients. The proteins have chemical modifications such as succmylation, deammation, glytarylation or phosphorylation which decrease the isoelectric point of the protein compared to the protein's native isoelectric point and enhance protem-protem interactions, thereby reducing solubility and swelling, and delaying release of the active ingredient when the formulation is ingested orally. Particularly, the invention relates to tablets that comprise an excipient of chemically-modified food proteins such as soy proteins or -lactoglobulm useful for delaying release of an active ingredient such as a pharmaceutical drug or a probiotic.

Abstract: A new process for the manufacture of iodinated xanthenes in high purity includes a cyclization step followed by an iodination step. No extraction, chromatographic or solvent concentration steps are required, and the intermediate as well as final compounds are isolated via filtration or similar means. The process requires a single organic solvent, and the steps are completed at temperatures below 100° C. The exclusion of chloride ions, of chloride free-radicals, hypochlorite ions, or hypochlorous acid as reagents or from reagents that may generate these species in situ in the presence of oxidants, prevents undesirable impurity formation. Several new compounds have been conceived and isolated using these methods. These new compounds are also formed into new medicaments.

Abstract: The present invention provides a method of forming an ion of formula (I) comprising the steps of: (i) reacting a compound of the formula (IIa); with a biopolymer, BP, having at least one group capable of reacting with M to form a covalent linkage, to provide a biopolymer derivative of the formula (IIIa); and (ii) cleaving the C—X bond between X and the ?-carbon atom of the derivative of formula (IIIa) to form the ion of formula (I); where: (IV) is a carbon atom bearing a single positive charge or a single negative charge; and X is a group comprising a thioether sulphur atom bound directly to the ?-carbon which is capable of being cleaved from the ?-carbon atom to form an ion of formula (I). The biopolymer derivatives of the invention have enhanced ionisability with respect to free biopolymer (BP) enabling improved analysis of the biopolymer using mass spectrometry.

Abstract: Peptides have been identified that bind to oral surfaces such as teeth and gums. Peptide based oral care reagents have been created by couple such peptides to oral care benefit agents such as whiteners.

Abstract: This invention is a method of using a class of excipients for protein formulation to reduce and/or eliminate protein aggregation in solutions or solids. This class of compounds contains carbonyl group(s) to form Schiff base(s) with amino groups of proteins and also contains moieties to keep protein molecules spatially separated. This method has never been disclosed anywhere in the literature.

Abstract: A method for renaturation of proteins comprising adding to a solution of denatured, chemically modified or reduced proteins a refolding buffer containing a primary, secondary or tertiary amine. Said method has been applied, for example, to interleukin-4 and bovine pancreatic trypsin inhibitor (BPTI), which were previously (i) solubilized in the presence of guanidinium hydrochloride as chaotronic agent, and (ii) subjected to sulfitolysis.

Abstract: The current invention reports a method for the purification of a not-glycosylated, heterologous polypeptide, which has been recombinantly produced in a prokaryotic cell, wherein the method comprises three chromatography steps of which the first chromatography step selected from i) hydrophobic charge induction chromatography, or ii) hydrophobic interaction chromatography, or iii) affinity chromatography, or iv) ion exchange chromatography, the second chromatography step is selected from i) anion exchange chromatography, or ii) cation exchange chromatography, or iii) hydroxylapatite chromatography, or iv) hydrophobic interaction chromatography, and the a third chromatography step is selected from i) hydrophobic charge induction chromatography, or ii) anion exchange chromatography, or iii) cation exchange chromatography, or iv) hydrophobic interaction chromatography, whereby the first chromatography step is an affinity chromatography in case of polypeptides capable of interacting with metal ligands, the second c

Abstract: The growth hormone with high biological activity modified by the double-stranded polyethylene glycol at a single site and the preparation method thereof are provided. The PEGylated growth hormone has a higher biological activity and a longer half-life than the unmodified growth hormone. The composition comprising the PEGylated growth hormone is useful in the treatment of the growth or development disorder such as growth hormone deficiency, Turner syndrome etc.

Abstract: Segmented water soluble polymers, containing a higher molecular weight segment linked to a lower molecular weight segment, are described. In one embodiment, the polymer segments are poly(ethylene glycol) segments. The segmented polymers are functionalized and are useful for conjugation to various moieties such as pharmacologically active substances. Also described are conjugates of such polymers and methods of their preparation.

Abstract: An immobilization method for immobilizing a physiologically active substance on a solid phase carrier, the method including: bringing the solid phase carrier into contact with an acid anhydride functional group-containing silane coupling agent represented by the following Formula (I); and carrying out a process of binding of the physiologically active substance to the acid anhydride functional group while maintaining the solid phase carrier after the contact at a temperature within the range of 0° C. to 60° C.; a physiologically active substance-immobilized carrier, and a carrier for immobilization are provided. Further, a carrier including a porous material treated with an acid anhydride functional group-containing silane coupling agent represented by the following Formula (I), a blocking agent that is immobilized to the porous material; and a method for producing it is provided.

Abstract: It is an object of the present invention to obtain a labeled protein, and specifically, to separate a labeled protein and the same unlabeled protein. There is provided a labeled protein including: a protein to be labeled having a target protein, at least one or more affinity interaction domains for binding to an affinity support, and at least one or more labeling sites; and a labeling reagent binding to at least one of the labeling sites; wherein the affinity of the labeled protein for the affinity support is difference from that of the protein to be labeled for the affinity support.

Abstract: It is an object of the present invention to provide a method for chemically modifying biopolymer and polypeptide with a hydrophobic compound or a compound which causes degradation or reaction under basic condition. The present invention provides a method for producing a chemically modified biopolymer or polypeptide, wherein a biopolymer or polypeptide is chemically modified in a reaction solution containing an organic fluorine compound.

Abstract: The invention provides amphiphilic compounds and methods for manipulating membrane proteins. Compounds of the invention, for example, the compounds of Formulas I-XIX, can be prepared from readily available starting materials. The amphiphilic compounds can manipulate membrane protein at relatively low concentrations compared to many known detergents. The compounds can be used to aid the isolation of membrane proteins, for example, to aid their solubilization and/or purification. The compounds can also be used to aid the functional and structural determination of membrane proteins, including their stabilization and crystallization.

Abstract: The present invention relates to a method for preparing poloxamer-protein particles. It also relates to poloxamer-protein particles obtainable by this method, dispersion thereof, and their use in methods of encapsulation, in particular of microencapsulation.

Abstract: The invention relates to transmembrane protein pore for use in detecting a analyte in a sample. The pore comprises a molecular adaptor that facilitates an interaction between the pore and the analyte. The adaptor is covalently attached to the pore in an orientation that allows the analyte to be detected using the pore.

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: Provided herein are methods for refolding proteins. The methods involve covalently modifying a denatured protein with a nonproteinaceous polymer and then renaturing the modified protein.

Abstract: In certain embodiments, this present invention provides polypeptide compositions, including compositions containing a modified polypeptide, and methods for inhibiting Ephrin B2 or EphB4 activity. In other embodiments, the present invention provides methods and compositions for treating cancer or for treating angiogenesis-associated diseases.

Abstract: The present invention refers to soluble Neuregulin-1 isoforms representing Posttranslational Neuregulin-1 modifications as medication in cognition-related neurological disorders, in particular schizophrenia, Alzheimer's and Parkinson's diseases.

Abstract: The invention provides a novel process for conjugating a polymer, especially PEG, to a protein or peptide, which comprises reacting a polymeric conjugation reagent with a protein or peptide containing a polyhistidine tag under conditions such that conjugation occurs via said polyhistidine tag. The resulting conjugates are novel.

Abstract: [Purpose] A purpose of this invention is to provide a robust and flexible free-standing ultrathin (nano) or thin pure protein membrane which enables a rapid and simple separation (or condensation) of relatively small (M.W.=ca. 1,000 Da) molecules. [Summary] A flexible free-standing ultrathin (nano) or thin protein membrane can be fabricated by a method comprising following steps: (1) A dilute metal (Cd, Cu or Zn) nitrate or chloride solution is kept under neutral or weak basic pH to spontaneously form metal (Cd, Cu or Zn) hydroxide nanostrands; (2) The above metal (Cd, Cu or Zn) hydroxide nanostrands and protein solution are mixed to obtain composite nanofibers made of protein and the said metal hydroxide nanostrands; (3) The obtained dispersion of composite nanofibers is filtered on a filter. (4) Proteins contained in the composite nanofibers are cross-linked by bifunctional cross-linkers; and (5) Metal (Cd, Cu or Zn) hydroxide nanostrands are removed from them.

Abstract: The invention relates transiently attaching drag-tags to molecules during electrophoresis. The invention includes running buffers having drag-tags that transiently attach to lipophilic moieties attached to the molecules. The lipophilic moieties can be covalently or ionically bonded to the molecules. One particular aspect of the invention is a nucleoside analog or a nucleic acid analog comprising a lipophilic moiety. The invention is also directed to methods of separating molecules that comprise a lipophilic moiety. The methods generally comprise transiently attaching a drag-tag to the lipophilic moiety during a separation modality. These methods can be used to separate the molecules by size or weight, to measure a hydrodynamic radius of a drag-tag, or to separate a plurality of drag-tag by their hydrodynamic radius.

Abstract: The present invention provides an anti-tumor or anti-angiogenesis medicament, the combination or kit containing the medicament, and the method for producing the same. The anti-tumor or anti-angiogenesis medicament contains a conjugate comprising a modifying agent and the angiostatin or its fragments, wherein the conjugate exhibits prolonged in vivo half-life as compared to an unmodified angiostatin or its fragments. The modifying agent is selected from the group consisting of macromolecular polymers, protein molecules or fragments thereof, peptides, small molecules, or chemical substances of any other forms.

Abstract: Novel compositions comprising genipin for cross-linking polymer fibers, are provided. In aspects of the invention the compositions further comprise a solvent system, wherein said solvent system comprises alcohol solvent and water. The genipin-based compositions are useful in methods for promoting the stabilization of fibers in an aqueous environment, and in tissue engineering. The novel genipin-based composition is also useful in methods of treating dermatological conditions.

Abstract: A method for preparing a site-specific peptide probe, wherein the peptide is specific to a receptor, includes modifying a marker to include a tether molecule and covalently binding the tether molecule to the peptide. The present invention also provides a labeled probe, comprising a peptide specific for a receptor and a marker. The marker is modified to include a tether molecule capable of covalently binding to the peptide. The peptide is typically derived from a bacteriophage or is a synthetic analog or derivative of the peptide. The receptor will typically be found on a surface of a bacterial cell. The method and probe of the invention are suitable for a rapid assay for a bacteria in a complex mixture.

Abstract: A refolding agent and refolding method which makes it possible to produce high-purity proteins in high productivity. The refolding agent includes a phosphorus-containing compound (A) and an oxycarbonyl group-containing compound (B). The refolding method includes the step of treating the unfolded protein with the refolding agent. As the compound (A), there may be at least one selected from inorganic phosphoric acids, alkyl phosphate esters, sugar phosphate esters, and salts of these, and as the compound (B), there may be at least one selected from formic acid, acetic acid, propionic acid, lactic acid, tartaric acid, and salts of these.

Abstract: This invention relates to the use of a cyclic compound of formula (I) wherein A, B independently in each occurrence is alkane-i,j-diyl having k carbon atoms, i and independently j being less than or equal k and k being selected from 1 to 10, wherein said alkane-i,j-diyl (i) may comprise one or more double bonds; (ii) is optionally substituted; and/or (iii) comprises a cycle, wherein the total number of cycles being cyclic sugars in said compound is selected from 0 to 4 and is less than p·n+m); X,Y independently in each occurrence is a biocompatible functional group comprising at least one oxygen atom or two sulphur atoms; n, m independently of each other are selected from 0 to 20; p is selected from 1 to 10; n+m is equal or greater than 1; and p·(n+m) is selected from 3 to 30; wherein said compound is capable of forming a complex with a protonated primary and/or protonated secondary amino group and/or a protonated guanidinium group for the manufacture of a pharmaceutical or diagnostic composition further

Abstract: The present invention relates to methods for complexing a protein in a dispersed medium. Also disclosed are associated proteins produced by the methods of complexing of the present invention. Pharmaceutically effective stabilized protein dosages are also disclosed. The present invention also relates to a method for associating AHF protein in a dispersed medium.

Abstract: Biocompatible implants include a polymer substrate and a reactive component selectively applied to the substrate. The reactive component in combination with the substrate creates crosslinked regions on a surface of the substrate. The crosslinked regions may provide a visual aid and/or stiffening element to the implant.

Abstract: The invention relates to a process for modifying allergens to enhance their suitability in immunotherapy. The invention further relates to the modified allergens and pharmaceutical compositions thereof, as well as to their use in immunotherapy.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: The present invention relates to the tagging of Histidine in polypeptides with arylboronic acid tagging reagents. The present invention further describes methods and devices to identify proteins in a sample by isolating and identifying Histidine-comprising peptides from one protein sample or a pool of protein samples. The present invention further describes databases of Histidine-comprising peptides from in silico cleaved proteins and their use in the identification of proteins.

Abstract: The invention is concerned with N-terminally pegylated polypeptides capable of binding to the prolactin receptor. Such polypeptides may for instance be N-terminally pegylated antagonists of the prolactin receptor, such as for instance prolactin variants.

Abstract: Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural ? amyloid peptides (?-AP). In a preferred embodiment, the ? amyloid modulator compounds of the invention are comprised of an A? aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural ? amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural ?-AP aggregation when the natural ?-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

Abstract: Biocompatible phase invertible proteinaceous compositions and methods for making and using the same are provided. The subject phase invertible compositions are prepared by combining a proteinaceous substrate and a crosslinking agent, such as a stabilized aldehyde crosslinking agent. Also provided are kits for use in preparing the subject compositions. The subject compositions, kits and systems find use in a variety of different applications.

Abstract: Provided herein is a straightforward and efficient method for covalently attaching a polyethylene glycol polymer to an active agent.

Abstract: Galectin 9, which is an immune function-controlling factor belonging to a new class that is different from known cytokines and is expected to be used as a therapeutic drug for various immune-related diseases such as an autoimmune disease, has disadvantages (such as high sensitivity to protease and poor solubility) to be solved in developing therapeutic drugs. Therefore, there is a need to overcome these disadvantages. Chemically modified galectin 9, prepared by conjugating a polymer (for example, poly(ethylene glycol: PEG) to galectin 9, in particular, stabilized galectin 9, is verified to exert higher solubility with improvements in pharmacodynamics and pharmacokinetics (for example, prolongation of action potential duration, such as prolongation of blood half-life and others) and in suppression of hemagglutination and thus has excellent characteristics as a drug.

Abstract: The present invention relates to novel polymer conjugates of polypeptide variants of the HMGB1 high affinity binding domain Box-A (HMGB1 Box-A) or of a biologically active fragment of HMGB1 Box-A. Further, the invention relates to novel polymer conjugates of polypeptide variants of the HMGB1 high affinity binding domain Box-A (HMGB1 Box-A). Moreover, the present invention concerns the use of said polymer conjugates of polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and/or associated with an increased expression of RAGE.

Abstract: A method for conjugation of glycosylated Fc-containing proteins is described. The method comprises carbamate chemistry performed and neutral pH or below and the resulting Fc-containing protein are expected to retain tertiary structure and therefore Fc-related bioactivity such as FcR binding, the ability to bind Clq, in addition to retaining ligand binding capabilities related to the incorporation of a ligand binding peptide or other polypeptide which has binding specificity. The method is exemplified using an erythropoietin-mimetic peptide fused to a human IgG1 antibody constant domain comprising a hinge, CH2 and CH3.

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 method of ligating two or more molecules, for example, peptides to peptides or peptides to labels is provided. The method may comprise the steps: a) providing a first oligopeptide having a reactive moiety, which is a hydrazine moiety, a hydrazide moiety or an amino-óxy moiety b) providing a second oligopeptide having an activated ester moiety, c)allowing the reactive moiety of the first oligopeptide to react with the activated ester moiety of the second oligopeptide to form an oligopeptide product, in which the first and second oligopeptides are linked via a linking moiety having Formula I, II or III. The second oligopeptide may preferably be generated by thiol reagent induced cleavage of an intein fusion protein. The invention further provides labelling and ligation methods in which protein hydrazides are ligated by reaction of the hydrazide moiety with an aldehyde functionality or a ketone functionality.