Abstract: Described herein are processes for the preparation of compounds of formula (I): and pharmaceutically acceptable salts, solvates, and hydrates thereof.

Abstract: The present invention provides nucleosides of formula (1) and oligonucleotides comprising at least one nucleoside of formula (2): Another aspect of the invention relates to a method of inhibiting the expression of a gene in cell, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.

Abstract: The invention relates to the synthesis of peptides, proteins and related bioconjugates, and in particular, to such synthesis using a peptide ligation method whereby a C-terminal salicylaldehyde ester peptide is reacted with an aminoacyl-N-hydroxl peptide. The invention also relates to the synthesis of cyclic peptides, including serinyl- or threonyl-containing cyclic peptides. The invention further relates to a solid phase synthesis of C-terminal salicylaldehyde ester peptides.

Abstract: A process of purifying the Growth Factor Protein G-CSF (Granulocyte Colony Stimulating Factor) in a purification sequence employing chromatography, comprising binding the G-CSF to Capto MMC™, which is a multimodal resin that comprises a negatively charged 2-(benzoylamino) butanoic acid ligand, at a pH from 4 to 6.2; and eluting the G-CSF at a pH greater than 6.3.

Abstract: Disclosed are methods of purifying mixtures comprising benzoidiazepine antibody-drug conjugates.

Abstract: The invention relates to compounds of Formula I: and pharmaceutically acceptable salts and prodrugs thereof, wherein R1, R2, and R3 are defined as set forth in the specification. The compounds are agonists of neurotrophin (such as nerve growth factor) receptors.

Abstract: There are disclosed compounds of formula (I) that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing said compounds.

Abstract: Disclosed herein is a species of peptide and non-peptide inhibitors of Akt, an oncogenic protein. Beginning with a residue of Akt target substrate GSK-3, the functional domains of the GSK-3 residue were characterized. Functionally homologous non-peptide groups were substituted for the amino acids of the GSK-3 creating a hybrid peptide-non-peptide and non-peptide compounds capable of binding to Akt. The non-peptide compounds show increased stability and rigidity compared to peptide counterparts and are less susceptible to degradation. The bound non-peptide compounds exhibit an inhibitory effect on Akt, similar to peptide-based Akt inhibitors.

Abstract: Isolated peptides, compositions and methods of use for treating tumors infiltrated with macrophages, such as glioblastomas.

Abstract: The present invention relates to novel cyclosporin derivatives that do not cross the cellular membrane. The compounds according to the invention are used in medicine, more particularly in the treatment/diagnosis of acute and chronic inflammatory diseases, viral infections, cancer, degenerative muscle diseases, neurodegenerative diseases and damage that is associated with calcium homeostasis impairment. The novel cyclosporin derivatives additionally have no immunosuppressive effect.

Abstract: The present invention relates to a pharmaceutical composition comprising a cyclotide for use in immune suppression as well as to a method for immune suppression comprising the step of administering an effective amount of a pharmaceutical composition comprising such a cyclotide to a subject in need thereof. The present invention also relates to a pharmaceutical composition comprising a cyclotide for use in treating or preventing a disorder selected from the group consisting of (i) an autoimmune disorder; (ii) a hypersensitivity disorder; and (iii) a lymphocyte-mediated inflammation. Likewise, the present invention also relates to a method for treating or preventing a disorder selected from the group consisting of (i) an autoimmune disorder; (ii) a hypersensitivity disorder; and (iii) a lymphocyte-mediated inflammation.

Abstract: The present invention relates to shortened peptides comprising a muscle function enhancing amino acid sequence which is derived from the S100 calcium binding protein family. Furthermore, the present invention provides said peptides for medical use, in particular, for treating or preventing disorders associated with muscular malfunction, such as skeletal muscle or cardiac muscle disorders. The present invention also provides a pharmaceutical compositions comprising said peptides and a method for treating or preventing disorders associated with muscular malfunction using said peptides or said pharmaceutical compositions.

Abstract: The present invention refers to methods for selectively recognizing a base pair in a DNA sequence by a polypeptide, to modified polypeptides which specifically recognize one or more base pairs in a DNA sequence and, to DNA which is modified so that it can be specifically recognized by a polypeptide and to uses of the polypeptide and DNA in specific DNA targeting as well as to methods of modulating expression of target genes in a cell.

Abstract: The present inventors improved methods for inactivating Japanese encephalitis virus vaccines, and assessed the safety of vaccines produced by combining multiple vaccines. The present inventors successfully produced safer Japanese encephalitis vaccines by cell culture, which can be stored more stably over a long period than conventional Japanese encephalitis vaccines. Furthermore, it is also expected that the production methods can be used to produce other viral vaccines with excellent storage stability.

Abstract: A nucleic acid includes, in the following order, a 5? untranslated region comprising a particular nucleotide sequence of the genome of hepatitis C virus genotype 3a; a nucleotide sequence encoding a particular amino acid sequence of an NS3 protein, a nucleotide sequence encoding a particular amino acid sequence of an NS4A protein, a nucleotide sequence encoding a particular amino acid sequence of an NS4B protein, a nucleotide sequence encoding a particular amino acid sequence of an NS5A protein, a nucleotide sequence encoding a particular amino acid sequence of an NS5B protein of the hepatitis C virus genotype 3a; and a 3? untranslated region comprising a particular nucleotide sequence of a genome of hepatitis C virus genotype 3a.

Abstract: The present invention provides a novel isolated plasmid, wherein the plasmid is a native plasmid found in unique C. botulinum type A strains and encode either BoNT/A3 or BoNT/A4 and BoNT/B. The present invention also provides a method of obtaining a plasmid-encoded botulinum neurotoxin and botulinum neurotoxin complex comprising the step of isolating a plasmid encoding the cntA/A or cntA/B neurotoxin gene and genes encoding protein components of the toxin complex from a C. botulinum type A strain. The inventors performed comparative analyses of representative BoNT/A subtype strains by pulsed-field gel electrophoresis (PFGE) and Southern hybridizations with probes specific for the BoNT/A and B genes, cntA/A and cntA/B. Unexpectedly, the inventors determined that the genes encoding BoNT/A3 in the A3 strain, and BoNT/A4 and BoNT/B in the A4 strain, are on plasmids.

Abstract: The invention relates to pharmaceutically important variants of the major allergen Phl p 1 from timothy grass, characterized in that a preparation, hitherto not possible, of monomeric molecules which are soluble and stable in physiological media can be carried out with the aid of prokaryotic expression systems and subsequent purification thereof.

Abstract: The invention relates to immunostimulatory oligonucleotides and methods of using immunostimulatory oligonucleotides to induce an antigen-specific immune response. The invention further relates to a vaccine that comprises an immunostimulatory oligonucleotide and an antigen, and comprises a pharmaceutically acceptable carrier. The immunostimulatory oligonucleotides of the invention, in some embodiments, include one or more modified linkage(s).

Abstract: Provided are compositions and methods for efficient delivery of polynucleotides and/or small molecules to or into cells. The compositions comprises a peptide which as an excess positive charge and self assembles into homopentamers. The homopentamers can non-covalently bind polynucleotides. When encapsulated in lipid systems, such as liposomes, the lipoproteoplexes so formed, are capable of delivering both nucleic acids and small molecules to cells.

Abstract: Therapeutic compositions for treatment of protein serine/threonine phosphatase-related diseases are obtained by engineering amino acid sequences that disrupt interaction between the protein serine/threonine phosphatase and a protein inhibitor and are provided herein. Calcineurin and PPI are examples of protein serine/threonine phosphatases. RCAN1 is an inhibitor of calcineurin and is overexpressed in patients with serious diseases, such as Down syndrome and Alzheimer's disease. Molecules that bind RCAN1 at regions that interact with calcineurin selectively modulate functions of calcineurin to treat these diseases. Methods of treating a subject for a protein serine/threonine phosphatase-related disease by administering a molecule having an amino acid sequence selected from the group of SEQ ID NOs: 1-19 are further provided.

Abstract: The present invention provides a GIP analog, which is derived from GIP (1-29, SEQ ID NO: 1), has both GLP-1 agonist activity and GIPR stimulation activity, and comprises an amino acid sequence represented by the following formula I: Tyr-A2-A3-Gly-Thr-Phe-A7-Ser-Asp-Tyr-Ser-A12-A13-A14-A15-Lys-A17-A18-A19-A20-A21-A22-A23-A24-Trp-Leu- A27-A28-A29-Y. The present invention also provides a pharmaceutical composition comprising the GIP analog and use thereof.

Abstract: The present invention relates generally to novel, selectable hybrid polypeptides useful as agents for the treatment and prevention of metabolic diseases and disorders which can be alleviated by control plasma glucose levels, insulin levels, and/or insulin secretion, such as diabetes and diabetes-related conditions. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.

Abstract: GLP-2 analogs are disclosed which comprise one of more substitutions as compared to h[Gly2]GLP-2 and which may have the property of an altered GLP-1 activity, and their medical use. The analogs are particularly useful for the prophylaxis, treatment or ameliorating of the gastro-intestinal associated side effects of diabetes.

Abstract: The disclosure relates to the field of GPCR structure biology and signaling. In particular, it relates to protein binding domains directed against or capable of specifically binding to a functional conformational state of a G-protein-coupled receptor (GPCR). More specifically, it provides protein binding domains that are capable of increasing the stability of a functional conformational state of a GPCR, in particular, increasing the stability of a GPCR in its active conformational state. The protein binding domains hereof can be used as a tool for the structural and functional characterization of G-protein-coupled receptors bound to various natural and synthetic ligands, as well as for screening and drug discovery efforts targeting GPCRs. Moreover, also encompassed are the diagnostic, prognostic and therapeutic usefulness of these protein binding domains for GPCR-related diseases.

Abstract: Disclosed are: an Fc binding protein having increased stability with respect to heat, acid, and/or alkalinity compared with the wild type; a method for producing same; and a method for specifically isolating protein containing an Fc binding protein binding site using said Fc binding protein as a ligand for affinity chromatography. An Fc binding protein was obtained having increased stability with respect to heat, acid, and/or alkalinity compared with the wild-type human Fc receptor by means of substituting at least one specific amino acid residue in the extracellular domain of the wild-type human Fc receptor with another amino acid residue. The Fc binding protein is useful as a ligand for affinity chromatography for example by immobilizing in a solid phase.

Abstract: The present invention relates to stable pharmaceutical liquid formulations of the fusion protein TNFR:Fc comprising different buffer systems and stabilizers. In particular, it could be demonstrated that the physical stability of TNFR:Fc is significantly improved by using a citrate buffer system and lysine as stabilizer.

Abstract: This disclosure provides antibodies that specifically bind to and typically neutralize botulinum neurotoxins (e.g., BoNT/A, BoNT/B, BoNT/E, etc.) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism.

Abstract: A diagnostic test for preclinical and clinical Alzheimer's disease is based on plasma levels of A?40, A?42, their ratio, or their rate of entry following administration of antibodies that sequester A?. Alterations of any of these parameters from control values identifies preclinical or clinical Alzheimer's disease.

Abstract: The inventors discovered that the adhesion molecule CAR, known to be localized in intracellular adhesion sites, functioned as an adhesion molecule for activated lymphocytes. Further, the inventors identified CARL, a novel CAR ligand expressed in lymphocytes, and clarified that the ligand was expressed selectively in Th1 cells. In addition, they found that anti-CAR antibodies could inhibit the adhesion of activated lymphocytes to CAR molecules. Thus, the present invention provides methods for detecting Th1 cells using CAR or anti-CARL antibodies, and methods of screening for inhibitors suppressing the adhesion of Th1 cells using the binding between CAR and CARL as an index. Furthermore, the present invention relates to methods of screening for inhibitors of the binding between CAR and CARL, antibodies that inhibit the binding between CAR and CARL, and therapeutic compositions comprising these antibodies.

Abstract: The invention relates to binding partners of the placental growth factor (or placenta growth factor, PlGF), especially antibodies directed against the placental growth factor, and production and use thereof.

Abstract: The present invention provides antibodies that bind to interleukin-33 (IL-33) and methods of using the same. The invention includes antibodies that inhibit or attenuate IL-33-mediated signaling. The antibodies of the invention may function to block the interaction between IL-33 and ST2. Alternatively, certain antibodies of the invention inhibit or attenuate IL-33-mediated signaling without blocking the IL-33/ST2 interaction. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human IL-33 with high affinity. The antibodies of the invention are useful for the treatment of diseases and disorders associated with IL-33 signaling and/or IL-33 cellular expression, such as inflammatory diseases, or allergic diseases.

Abstract: Provided are monoclonal antibodies, or antigen-binding fragments thereof, that bind to glucagon. These antibodies are useful in immunoassays of glucagon levels, and/or in vivo, ex vivo or in vitro immunochemical and other imaging methods for detecting glucagon levels, and for diagnostic, prognostic and predictive purposes, and for optimizing therapeutic regimens in patients in which glucagon signaling is implicated in pathogenesis.

Abstract: The present invention includes compositions and methods for making and using anti DC-ASGPR antibodies that can, e.g., activate DCs and other cells.

Abstract: Antigen binding proteins with TCR-like paratopes, that is, with an antigen binding region specific for an HLA-A2 restricted peptide are disclosed. The antigen binding proteins encompass antibodies in a variety of forms, including full-length antibodies, substantially intact antibodies, Fab fragments, F(ab?)2 fragments, and single chain Fv fragments. Fusion proteins, such as scFv fusions with immunoglobulin or T-cell receptor domains, incorporating the specificity of the antigen binding region for each peptide are also contemplated by the invention. Furthermore, immunoconjugates may include antibodies to which is linked a radioisotope, fluorescent or other detectable marker, cytotoxin, or other molecule are also encompassed by the invention. Among other things, immunoconjugates can be used for delivery of an agent to elicit a therapeutic effect or to facilitate an immune effector function.

Abstract: Disclosed are antibodies that specifically bind Toll-like Receptor 4 (TLR-4), and to methods of using the anti-TLR4 antibodies as therapeutics and diagnostic agents.

Abstract: The present invention provides isolated human monoclonal antibodies that bind to IFNAR-1 and that are capable of inhibiting the biological activity of Type I interferons. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting Type I interferon-mediated disorders using the antibodies of the invention, including methods for treating autoimmune disorders, transplant rejection or Graft Versus Host Disease using the antibodies of the invention.

Abstract: The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolyzed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolyzing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

Abstract: The invention provides antibodies to specific neural proteins and methods of using the same.

Abstract: This disclosure relates to antagonistic dual receptor antigen-binding proteins, e.g. antibodies and methods of using the dual receptor antibodies for treatment of pathological diseases. The dual receptor antibodies may comprise an antibody to ActRII receptors and may be used to treat pathological condition. The pathological conditions can comprise muscle wasting diseases or any disease that requires stimulation of muscle growth.

Abstract: A reaction product mixture is obtained from a reaction of (a) a cellulose ether with (b) an aliphatic monocarboxylic acid anhydride or with a di- or tricarboxylic acid anhydride or with a combination of an aliphatic monocarboxylic acid anhydride and a di- or tricarboxylic acid anhydride in the presence of (c) an aliphatic carboxylic acid. A process for precipitating an esterified cellulose ether from this reaction product mixture comprises the step of contacting the reaction product mixture with water and subjecting the combination of water and the reaction product mixture to a shear rate of at least 800 s?1. The precipitated esterified cellulose ether can be recovered as a non-tacky product.

Abstract: There is provided a composition comprising a polysaccharide obtainable from the microalgae, Prasinococcus capsulatus and strains related to P. capsulatus for use prophylactically and/or therapeutically in the treatment of disorders of the immune system, for example in psoriasis and dermatological conditions, internal immune system disorders, in particular gut inflammatory conditions and respiratory conditions. Further, there is provided derivatives of a polysaccharide obtainable from the microalgae, Prasinococcus capsulatus or an algal strain related to P. capsulatus and the use of such derivatives prophylactically and/or therapeutically in the treatment of disorders of the immune system.

Abstract: A method of producing vinyl polymer particles by suspension polymerization comprising: combining an aqueous media and a tricalcium phosphate to a reaction vessel; adding a pH stabilizing agent to the reaction vessel; adding a vinyl monomer to the reaction vessel; adding a peroxide initiator, e.g., which also generates CO2 as a result of primary or secondary decomposition, to the reaction vessel; adding surfactant or a water soluble free radical initiator to generate surfactant in situ to the reaction vessel; maintaining the reactor contents at greater than or equal to 90° C. until a density of a dispersed phase becomes substantially equal to that of a continuous phase; adding a blowing agent to the reaction vessel; raising the temperature of the reaction vessel to greater than or equal to 100° C.; and collecting polymer particles having a particle size distribution.

Abstract: A polymer gel structure that includes a first layer having at least one non-planar main surface, the first layer including a first polymer component; and a second layer formed on the main surface of the first layer, the second layer including a second polymer component, wherein the second polymer component at least partially penetrates the first layer forming an interpenetrating polymer network structure or a semi-interpenetrating polymer network structure between the first polymer component and the second polymer component.

Abstract: An initiator composition, including at least two compounds represented by the chemical formula R—CO—O—O—CO—R and a compound represented by R1—O—O—R2, where R represents a C2-C12 alkyl or a C6-C10 aryl or substituted aryl, and R1 and R2 independently, at each occurrence, represent a C1-C10 alkyl or a C6-C10 aryl.

Abstract: Described herein is a composition comprising an aqueous polymerization reaction product of fluorinated monomers and wherein the polymerization is initiated (i) in the absence of a fluorinated emulsifier and whereby no fluorinated emulsifier is added during polymerization or (ii) in the presence of an fluorinated emulsifier selected from: [Rf—O-L-COO-]i Xi+ (I) wherein L represents a linear or branched, non-fluorinated, partially fluorinated, or fully fluorinated alkylene group, Rf represents a linear or branched partially or fully fluorinated aliphatic group or a linear or branched partially or fully fluorinated aliphatic group interrupted with at least one oxygen atom, Xi+ represents a cation having the valence i and i is 1, 2 or 3; wherein the reaction product and/or the resulting aqueous phase are substantially free of di- and tri-alkylamines and substantially free of low molecular weight fluoroorganic compounds and methods thereof.

Abstract: A synthesis method of ultra low molecular weight homopolymerized N-vinyl butyrolactam with ultra low residual monomer content is provided N-vinyl butyrolactam monomers and water are provided with the mass ratio of 3:17˜8:12 0.5%˜5.0% by weight of initiators, 0.1%˜5.0% by weight of a catalyst, and 0.1%˜10% by weight of a molecular weight regulator are provided in the presence of an inert gas, adding the above mentioned raw materials in batches, adjusting the pH of the reaction system to 7.0-8.0 with an activator, reacting at the polymerization temperature of 60-85° C. A peroxide is added and maintaining the temperature for 2 hours, to obtain an aqueous solution of ultra low molecular weight homopolymerized N-vinyl butyrolactam. The aqueous solution is dried to obtain a powdery ultra low molecular weight homopolymerized N-vinyl butyrolactam with ultra low residual monomer content.

Abstract: Prepolymerized catalyst component for the polymerization of olefins CH2?CHR in which R is hydrogen or a hydrocarbyl radical with 1-12 carbon atoms, having average particle size equal to or lower than 30 ?m comprising a solid catalyst component comprising magnesium halide, a titanium compound having at least a Ti-halogen bond and at least two electron donor compounds one of which being selected from 1,3-diethers and the other one being selected from esters of aromatic mono or dicarboxylic acids, said solid catalyst component being prepolymerized with an olefin, having from 2 to 10 carbon atoms, to such an extent that the amount of the olefin prepolymer is equal to or lower than 50 g per g of solid catalyst component.

Abstract: In one preferred embodiment, the present invention provides a process for the liquid phase polymerization of isobutylene to manufacture highly reactive PIB oligomers having Mn under 1000, using a catalyst composition comprising a Friedel-Crafts catalyst a complexing agent, a chain transfer agent and a polymerization-retarding agent. A chain transfer agent may be selected from: ?-DIB and ?-DIB and mixtures thereof.

Abstract: Process for producing a thermoplastic polymer foam article includes preparing an expandable polymeric formulation comprising a thermoplastic polymer and a blowing agent blend, forming the formulation into an expandable bead, and expanding the expandable bead to form a thermoplastic polymer foam article. The blowing agent blend includes methyl formate, hydrocarbon, and either carbon dioxide or 1,1,1,2-tetrafluoroethane (HFC-134a). The blowing agent blend has a higher effective volatility than that of methyl formate alone. A thermoplastic polymer foam article prepared by a process is also provided.

Abstract: A method for producing a water absorbent resin, the method including a polymerization step, a drying step, a classification step, and a surface crosslinking step. The classification step carried out before or after the surface crosslinking step requires use of a metal sieve mesh having stretch tension from 35 to 100 N/cm, in which an air jet cleaner or an air jet brush cleaner and plural tapping balls or tapping blocks are installed below the metal sieve mesh, a classification aid particle having specific gravity different from that of the water absorbent resin powder is added, and a fine powder of the water absorbent resin and the classification aid particle are removed.