Abstract: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract: The present invention relates to a process of preparing a Grignard reagent comprising reacting magnesium particulates in a fluid bed reactor. The present invention further relates to a continuous process comprising fluidizing magnesium particulates in a reactor, forming the Grignard reagent continuously, and reacting the Grignard reagent with a substrate.

Abstract: Compounds of formula (I) can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX).

Abstract: A process is provided for preparing a salt of a hydroxy-substituted ester of phosphoric acid, comprising: (a) reacting a phosphate diester with an alkylene oxide, (b) reacting the product mixture of step (a) with a phosphating agent; and (c) reacting the product mixture of step (b) with an amine; wherein the phosphate diester is reacted with the alkylene oxide of step (a) in the substantial absence of a phosphate monoester. The product is useful as an antiwear agent.

Abstract: Provided are a transition metal carbene complex represented by the following general formula (1) and a method of producing the same. (In general formula (1), M represents for example a molybdenum atom, R1 represents for example a C1-C20 alkyl group optionally having a substituent, L1 to L3 each represent a ligand selected for example from a halogen group, R2 and R3 each represent for example a hydrogen atom or a C1-C20 alkyl group optionally having a substituent. A represents for example a nitrogen atom, and R4 to R7 each represent for example a C1-C20 alkyl group optionally having a substituent.

Abstract: Platinum complexes that exhibit photoabsorption and photoemission, methods of making such complexes, and applications thereof are disclosed, including optical devices comprising the complexes.

Abstract: The invention provides novel compounds and compositions and methods for making and using the compounds and compositions. In particular, the use of organic acid salts promotes solubility. These more soluble forms are suitable for use in various diseases, notably diseases of lung, muscle, metabolism and eyesight.

Abstract: An amino acid conjugate of a cyclic or acyclic nucleoside phosphonate is provided. In some cases, the amino acid conjugate is a tyrosine alkyl amide phosphonate ester conjugate of a cyclic or acyclic nucleoside phosphonate, and is useful as an antiviral compound. In certain cases, the tyrosine conjugate includes a long chain alkyl group on the carboxamide group of the tyrosine residue. In a method of preparing an acyclic tyrosine conjugate, a tert-butyloxycarbonyl (Boc) protected tyrosine residue containing a long chain alkyl group is reacted with an acyclic nucleoside phosphonate mono-ethyl ester in the presence of benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate to produce a Boc-protected nucleoside phosphonate di-ester, and the di-ester is deethylated and deprotected to produce the tyrosine conjugate. Methods of inhibiting viral replication and methods of treating a viral infection using the amino acid conjugate are also provided.

Abstract: A way to formulate prasterone to both increase its oral bioavailability, and decrease the variability of its oral bioavailability. In contrast to the approach taught by the prior art, the instant approach is amenable to scale-up to commercial scale. Further, the resulting product is amenable to analysis using standard, known quantitative analytical techniques; thus, unlike the prior art approach, the instant approach may be used to manufacture a product in conformity with applicable regulatory standards.

Abstract: The invention is directed to a Ca2+ precipitable polypeptide tags and cassettes useful for purification of molecules from heterogeneous samples. The invention also relates to methods for bioseparation of molecules comprising Ca2+ precipitable tags and cassettes.

Abstract: Immunogens against human extended-progastrin species comprise (A) a mimetic peptide comprised of (i) the amino acid sequence of a progastrin or a N- and/or C-terminal processed species of a progastrin joined to (ii) a 7 amino-acid spacer coupled to (B) an immunogenic carrier. Illustrative of the mimetic peptide/spacer combination are a 21 amino-acid peptide (SEQ ID NO.: 1) and other, related polypeptides (SEQ ID NOs.: 2-5). Pharmaceutical compositions containing such an immunogen display improved immunological properties, including the induction of effective antibody levels shortly after the administration of an initial course of immunogen. Levels of antibody thus elicited stay elevated for several months and readily elevate to higher levels upon subsequent boosting by a single injection of immunogen.

Abstract: The present invention relates to the use of compounds selected from the group consisting of Lys-(D)Pro-Thr, N-acyl Lys-(D)Pro-Thr, C-amide Lys-(D)Pro-Thr, and C-esters of Lys-(D)Pro-Thr; or a pharmaceutically acceptable salt of said compound for the treatment of inflammatory disorders. The invention also relates to the use of ?MSH for inducing tolerance.

Abstract: The present invention refers to biochemistry, namely to new peptide compounds having the ability to selectively block the muscle-type nicotinic acetylcholine receptor. The claimed compounds have common formula (I): X1-X2-X3-Pro-X4-Pro-X5 (SEQ ID NO: 54), where X1 is chosen within H, Ac—, Palm-; X2 is chosen within Trp, Tyr; X3 is chosen within Trp, Tyr; X4 is chosen within Lys, Orn, Dbu, Dpr, Arg; X5 is chosen within —OH, —NH2, —OCH3, —OC2H5, —NH—C6H5. The invention can be applied in cosmetics for smoothing mimic and age-related Wrinkles.

Abstract: A dodecamer peptide, and its modified variant, having a repeating glycine-lysine sequence was created and found to bind with high affinity to oxide surfaces and certain activated polymeric surfaces. Reversible binding characteristics of the peptides were demonstrated. The peptides were integrated with proteins, cells and fusion proteins to provide attachment of the proteins, cells and fusion proteins to solid material structures. The peptides can be used to functionalize surfaces of components within mechanical, biomechanical, micro fluidic, electronic, bioelectronic, bio-optical, and biochemical devices. Experiments were carried out to assess functionalization and reusability of a suspended mass resonator's cantilever.

Abstract: The subject matter of the invention is an electroconducting nanowire, comprising an amyloid fiber which results from the self-assembling of peptides comprising a prion domain or a derivative of this domain and which is functionalized by electron transporting peptides, each comprising amino acids bound to one or more atoms of iron. Its subject matter is also a method of manufacturing this nanowire as well as the uses of said nanowire. Uses: manufacture of sensors for the detection of chemical or biological species, of nano-batteries, of radio-identification systems, of molecular memory systems, etc.

Abstract: The present invention relates to novel peptides and methods for treatment, diagnosis and prognosis of virus infections including infections with HCV, HIV, CMV and Influenza. The invention further relates to methods for identifying and providing peptides useful for the treatment and diagnosis.

Abstract: The present invention relates to synthetic proteins and the uses thereof. More particularly, the invention relates to synthetic Circovirus type capsid proteins with improved properties. These proteins, or the coding nucleic acids, are useful e.g., to generate antibodies, immunogen compositions, or vaccines. The invention further relates to methods for treating and/or preventing PCV2-associated diseases in mammals using said proteins, nucleic acids or compositions. The invention also relates to compositions and methods for detecting PCV2 in a sample, using the above proteins, nucleic acids, or antibodies.

Abstract: Intermolecular disulfide stabilized foldon polypeptides are provided.

Abstract: Meningococcal protein NMB 1870 has been described in the prior art. The inventors have found that NMB 1870 is an effective antigen for eliciting anti-meningococcal antibody responses, and that it is expressed across all meningococcal serogroups. Forty-two different NMB 1870 sequences have been identified, and these group into three variants. Serum raised against a given variant is bactericidal within the same variant group, but is not active against strains which express one of the other two variants i.e. there is intra-variant cross-protection, but not inter-variant cross-protection. For maximum cross-strain efficacy, therefore, the invention uses mixture comprising different variants of NMB 1870.

Abstract: Provided are ATP-binding cassette transporters (ABC transporters). More specifically, the present disclosure relates to ABC terpenoid transporters, nucleic acid sequences, amino acids, proteins, vectors, cells, transgenic organisms, uses, compositions, methods, processes, and kits thereof.

Abstract: The invention provides for peptides from syndecan 4 and methods of use therefor. These peptides can inhibit ?6?4 integrin interaction with EGFR, thereby preventing tumor cell growth and tissue invasion.

Abstract: This invention relates to the inhibition of expression or function of Men1 gene or its encoded proteins for the purpose of treating diabetes and screening and researching agents capable of inhibiting expression or function of Men1 gene or its encoded proteins for use in the treatment and diagnosis of diabetes.

Abstract: The present invention provides variant VEGF polypeptides which have been altered in their C-terminal heparin binding region to lower their heparin binding affinity. These variants have been found to act as receptor antagonists for VEGF receptors and antagonize angiogenesis. These variants are useful to treat diseases characterized by pathological angiogenesis.

Abstract: Methods of treating individuals with a glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.

Abstract: The present invention relates to an isolated chimeric protein. The isolated chimeric protein includes an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion from a fibroblast growth factor (“FGF”) 23 molecule and the C-terminus includes a C-terminal portion from an FGF19 molecule. The present invention also relates to a pharmaceutical composition including an isolated chimeric protein and a pharmaceutically acceptable carrier. The isolated chimeric protein includes an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion from a fibroblast growth factor (“FGF”) 23 molecule and the C-terminus includes a C-terminal portion from an FGF19 molecule, and a pharmaceutically-acceptable carrier. Yet another aspect of the present invention relates to a method for treating a subject suffering from a disorder.

Abstract: A method and a composition for decreasing ghrelin levels and/or decreasing ghrelin/unacylated ghrelin ratio in a subject, the method comprising administering an effective amount of unacylated ghrelin, a fragment thereof, an analog thereof and/or pharmaceutically acceptable salts thereof to the subject wherein a reduction in ghrelin levels and/or a reduction in ghrelin/unacylated ghrelin ratio is beneficial to the subject. Also, use of ghrelin level and/or ghrelin/unacylated ghrelin ratio as biomarkers for determining a subject's likelihood of responding to and/or benefiting from administration of unacylated ghrelin.

Abstract: Provided herein are methods for prophylactic treatment of renal disorders comprising administration of adrenocorticotropic hormone (ACTH), or fragment, analog, complex or aggregate thereof, or any combination thereof, to an individual suspected of having, predisposed to, or at risk of developing a renal disorder.

Abstract: An isolated nucleic acid encoding an FX protein having a serine at position 79, a lysine at position 90, a leucine at position 136, an arginine at position 211, a serine at position 289, and a combination thereof is provided. Cells having a gene encoding a modified FX protein are provided, wherein the cells exhibit a reduced ability to fucosylate a glycoprotein at a first temperature, but exhibit the ability to fucosylate the glycoprotein at a second temperature. Methods and compositions for making glycoproteins with reduced fucosylation are provided.

Abstract: A ligand includes each of the complementary-determining regions (CDRs) set forth in SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3 SEQ ID No. 4, SEQ ID No. 5 and SEQ ID No. 6 or any sequence having either number of substituted aminoacids within said sequences as indicated in the following, from 0 to 3 in CDR1 (SEQ ID No.1), from 0 to 2 in CDR2 (SEQ ID No.2), from 0 to 2 in CDR3 (SEQ ID No.3), from 0 to 1 in CDR4 (SEQ ID No.4), from 0 to 4 in CDR5 (SEQ ID No.5), from 0 to 2 in CDR6 (SEQ ID No.6), or aminoacids substituted with other aminoacids having equivalent chemical functions and properties, within said sequences SEQ ID No. 1 to SEQ ID No. 6.

Abstract: The present invention provides a humanized anti-HMGB1 antibody which specifically binds to a sequence consisting of the C-terminal 8 amino acid residues (EEEDDDDE) of HMGB1 protein and is effective for treatment or prevention of various inflammatory diseases related to this protein, as well as an antigen-binding fragment thereof. The present invention also provides a pharmaceutical composition comprising such an antibody or antigen-binding fragment thereof.

Abstract: Provided are glycoengineered populations of Fc domain-containing binding proteins with a reduced anti-drug immune response (ADA). Also provided are methods of treating disease using such compositions, and methods and host for making such compositions.

Abstract: The invention provides compositions and methods for ameliorating, treating, reversing or preventing pathology or inflammation in the central nervous system (CNS), or the brain, caused or mediated by NFkB, IL-6, IL-6-R, NADPH oxidase (Nox), and/or superoxide and/or hydrogen peroxide production by a NADPH oxidase, including for example ameliorating, treating, reversing or preventing schizophrenia, psychosis, delirium, e.g., post-operative delirium, drug-induced psychosis, psychotic features associated with frailty syndrome (FS), aging, depression, dementias; traumatic war neurosis, post traumatic stress disorder (PTSD) or post-traumatic stress syndrome (PTSS), Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's Disease), and/or Multiple Sclerosis (MS). The invention also provides methods for purifying a C60 fullerene, C3 (tris malonic acid C60) or malonic acid derivatives.

Abstract: A method of treating cancer or metastasis is provided involving administering at least one oncostatin M (OSM) antagonist to a subject, wherein the subject has been diagnosed with cancer. Administration of an OSM antagonist such as a small molecule pharmaceutical is provided as well as an anti-OSM antibody, an anti-OSM aptamer, and an OSM mRNA antagonist. The OSM antagonists were found to inhibit or prevent tumor cell detachment, proliferation and metastasis in several cancer types.

Abstract: The present invention relates to methods of treating liver cancer using a Notch signaling inhibitor. Compositions and methods for the treatment of liver cancers are also provided.

Abstract: The invention relates to antibodies that are capable of specifically binding TREM-1 and preventing the activation of TREM-1, a protein expressed on monocytes, macrophages and neutrophils. Such antibodies find utility in the treatment of individuals with an inflammatory disease, such as rheumatoid arthritis and inflammatory bowel disease.

Abstract: The present invention provides pharmaceutical composition for treating an autoimmune disease comprising a pharmaceutically acceptable carrier and an agent capable of activating CD4+CD25+ regulatory T cells, wherein the composition is to be administered to a subject at most every 3 days.

Abstract: The present invention relates to immunotherapies that are based on myeloid cell depletion. In particular, the present invention relates to CD33 binding agents for use in such therapies, e.g. in the treatment of myeloid cell malignancies and myelodysplastic syndrome (MDS).

Abstract: The present invention is aimed to provide a method for preparing an acceptor that is N-glycan hydrolyzed antibody or a Fc fragment thereof used for producing antibody having a homogeneous N-glycan structure; a method for determining a combination of endoglycosidases for use in said preparation; and a method for measuring N-glycans linked to an antibody. The present invention is directed to a method for producing a N-glycan hydrolyzed antibody or Fc fragment thereof, comprising reacting the antibody or the Fc fragment thereof with several endoglycosidases; and a method for determining quantitative information of an objective N-glycan with a desired structure linked to an antibody or a Fc thereof, comprising a protease treatment step and a glycopeptide measurement step, etc.

Abstract: As a result of producing anti-DDR1 antibodies and conducting extensive studies on the antitumor activity thereof, antibodies that bind to the stalk domain in the amino acid sequence of human DDR1 were found to have a potent activity even when used alone compared to antibodies that bind to other domains. It was also found that the antibodies have one or more activities selected from the group consisting of: (i) an activity to suppress cell proliferation, (ii) an activity to inhibit cell migration, (iii) an activity to inhibit phosphorylation of DDR1 in cells, (iv) an activity to be taken up into cells, (v) an activity to decrease the expression level of DDR1 in cells, and (vi) an activity to decrease the expression level of TGF-? in cells.

Abstract: The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), such as where the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof).

Abstract: An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.

Abstract: Disclosed herein are methods and compositions dock and lock (DNL) complexes comprising an AD moiety selected from an AKAP protein and a DDD moiety selected from a protein kinase A regulatory subunit. Also disclosed are fusion proteins comprising an AD moiety or DDD moiety attached to an effector moiety. The DDD moieties form dimers that bind to the AD moiety to form the DNL complexes. The effector moieties may be selected from a wide range of known effector moieties that produce one or more physiological effects, including but not limited to cell death. The DNL complexes may further comprise one or more diagnostic and/or therapeutic agents. The DNL complexes are of use for treating and/or diagnosing a variety of diseases or conditions.

Abstract: The present invention achieves increased filler interaction by incorporating a small amount (a few units per chain of rubbery polymer) of a conjugated triene monomer, such as alloocimene, randomly throughout the polymer chain of a rubbery polymer or at the chain ends of the rubbery polymer. The incorporation of the conjugated triene monomer leads to the formation of a polymer containing highly reactive conjugated diene units. These conjugated diene units can chemically react with carbon black leading to superior reinforcement. Alternatively, these conjugated diene units can be used for functionalization of the polymer with silica interactive/reactive groups using Diels Alder reactions. This functionalization of the rubbery polymer can conveniently be conducted in a mixer, such as a Banbury mixer, a mill mixer, or the like.

Abstract: To provide a producing method of conjugated diene rubber which can be used as a starting material of cross-linked rubber which is used for such as tire tread and can enhance low fuel consumption performance.

Abstract: A method of making a catalyst for use in oligomerizing an olefin comprising a chromium-containing compound, a pyrrole-containing compound, a metal alkyl, a halide-containing compound, and optionally a solvent, the method comprising contacting a composition comprising the chromium-containing compound and a composition comprising the metal alkyl, wherein the composition comprising the chromium-containing compound is added to the composition comprising the metal alkyl.

Abstract: Provided are an acrylic elastomer superior in adhesiveness to a fluorine-based elastomer, an acrylic elastomer composition containing the same, its laminate, and its crosslinked product and a molded article therefrom. Iodine groups are introduced as crosslinking groups into an acrylic elastomer to an iodine content of 0.1 to 2 mass % with respect to the total mass of the elastomer. In addition, 1 to 7 parts by mass of an organic peroxide and 1 to 5 parts by mass of an onium salt were blended with 100 parts by mass of the acrylic elastomer, to give an acrylic elastomer composition. Further, an acrylic elastomer layer of the acrylic elastomer composition is laminated with a fluorine-based elastomer layer of a fluorine-based elastomer composition mainly containing of a fluorine-based elastomer having iodine groups as crosslinking groups, to give a laminate. The laminate is then crosslinked to give a crosslinked product and a molded article.

Abstract: An object of the present invention is to provide a simple method for improving and stabilizing the physical properties (for example, liquid permeability) of a water absorbent resin, without requiring investment in expensive facilities or modification of raw materials. In particular, the object is to provide a method which is useful in the large-scale production of a water absorbent resin.

Abstract: Propylene homopolymer having a melt flow rate MFR2 (230° C.) at least 50 g/10 min, a Mw/Mn at least 12.0 and a xylene cold soluble content (XCS) of at least 2.8 wt.-%.

Abstract: The invention provides a polymer system, including a first composition and a second composition. The first composition is different from the second composition. The first composition includes a first gelator, the first gelator including a plurality of acylhydrazine moieties. The second composition includes a second gelator, the second gelator including a plurality of formyl moieties. At least one of the first composition and the second composition includes a prepolymer. The invention further provides a method of using the polymer system to form a polymeric material via multiple stages to more effectively control the rheology of the components over a variety of timescales.

Abstract: Novel urethane-acrylate (UAC) Star monomers and polyurethane-acrylate (PUAC) aerogel polymers derived therefrom are described herein, along with other novel, related monomers and polymers. Also described herein are processes for preparing the UAC Star monomers, the PUAC aerogel polymers, and the other related monomers and polymers. The PUAC and related polymers herein are useful in various applications including in structural and thermal insulation.