Thu, 25 Aug 2016 08:00:00 EDTThe invention relates to methods for monitoring progression of an inflammatory condition in a subject In particular embodiments the patient is undergoing treatment of the inflammatory condition and the method comprises monitoring the level of one or more biomarkers to monitor disease progression, for example to assist the clinician in optimising the treatment regimen. In particular embodiments the subject is undergoing treatment with mesenchymal stem cells (MSCs). In particular embodiments the invention relates to methods of monitoring the effectiveness of autologous or allogeneic cell therapy of a patient having a condition characterised by cartilage damage or degeneration, such as OA, for example in order to assist a practitioner in determining an appropriate time to administer a further dose of cells. The invention also provides kits and components for use in the methods.
Thu, 25 Aug 2016 08:00:00 EDTHIV-1's ability to enter a transcriptionally dormant state and establish a reservoir of latently infected cells is considered the major barrier to eradicating the virus from infected patients. Stochastic noise (i.e. fluctuations) in an HIV-1 transcriptional positive-feedback loop is one mechanism that enables HIV-1 to establish latency. Here, Applicants demonstrate that small-molecule modulation of noise in HIV-1 gene expression radically perturbs HIV-1 latency.
Thu, 25 Aug 2016 08:00:00 EDTIn one aspect there is provided a method for predicting a risk of unhealthy ageing in a subject, comprising: (a) determining a level of two or more lipid biomarkers in a sample from the subject, wherein the biomarkers are selected from two or more of the following groups: (i) a triacylglycerol (TAG) from TAG (46:5) to TAG (54:3); (ii) an ether phosphatidylcholine (PC-O) from PC-O(28:0) to PC-O(38:6); (iii) a sphingomyelin (SM) from SM (33:1) to SM(50:1); (iv) a phosphatidylcholine (PC) from PC (32:1) to PC (40:5); (v) a phosphatidylinositol (PI) from PI (36:1) to PI (38:3); (vi) a phosphatidylethanolamine (PE) from PE (36:2) to PE (38:4); and (b) comparing the levels of the biomarkers in the sample to reference values; wherein the levels of the biomarkers in the sample compared to the reference values are indicative of the risk of unhealthy ageing in the subject.
Thu, 25 Aug 2016 08:00:00 EDTNanomaterials fabricated to pharmaceutical dosage forms are disclosed. The nanomaterials are useful to provide a plurality of analysis to the dosage form. Consequently, the nanomaterials provide a means to perform quality testing on a continuous basis throughout the supply chain, including the cold chain whereby manufacturers and distributors can achieve greater product integrity and longer shelf life and ultimately minimize cost. The end user benefits in obtaining the highest quality drugs at the time of need.
Thu, 25 Aug 2016 08:00:00 EDTViral infection has been suspected in the development of primary Sjögren's syndrome (pSS). Using a custom viral microarray, hepatitis delta virus (HDV) genomes and antigens were detected in minor salivary glands of patients with pSS. Expression of HDV antigens in healthy mice led to a Sjögren's syndrome-like pathogenesis characterized by a reduction in salivary flow, increase in lymphocytic foci, and the development of an autoantibody profile similar to HDV-positive patients. Also described herein is the detection of HDV in patients diagnosed with lymphoma. Expression of HDV antigen in healthy mice resulted in the development of tertiary lymphoid structures characteristic of the early stages of lymphoma. A sensitive, nested qPCR assay to detect HDV transcript and/or HDV genome in patient samples is also described.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to a method of assessing whether a subject suffers from cancer or is prone to suffering from cancer, in particular lung cancer, comprising the measurement of the amounts of specific isoforms of GATA6 and/or NKX2-1 in a sample of said subject. Furthermore, the present invention relates to a composition for use in medicine comprising (an) inhibitor(s) of specific isoforms of GATA6 and/or NKX2-1. Additionally, the present invention relates to a kit for use in a method of assessing whether a subject suffers from cancer or is prone to suffering from cancer, in particular lung cancer.
Thu, 25 Aug 2016 08:00:00 EDTA recombinant vector comprises simian adenovirus SAdV-39, -25.2, -26, -30, -37, and -38 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus SAdV-39, -25.2, -26, -30, -37, and -38 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.
Thu, 25 Aug 2016 08:00:00 EDTProvided herein are Cocal vesiculovirus envelope pseudotyped retroviral vectors that exhibit high titers, broad species and cell-type tropism, and improved serum stability. Disclosed Cocal vesiculovirus envelope pseudotyped retroviral vectors may be suitably employed for gene therapy applications and, in particular, for the ex vivo and in vivo delivery of a gene of interest to a wide variety of target cells.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to a method for predicting the progression of chronic kidney disease (CKD) in a patient and also to an inhibitor of NGAL gene expression or an NGAL antagonist for use in the prevention or the treatment of CKD.
Thu, 25 Aug 2016 08:00:00 EDTThe invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.
Thu, 25 Aug 2016 08:00:00 EDTWhat is described is a lipid particle comprising the compound of formula I wherein R1 consists of alkyl, alkenyl, alkynyl, or cholesteryl;R2 consists of alkyl or alkenyl;L1 consists of alkyl, alkylene or alkenyl;X1 consists of —O—(CO)— or —(CO)—O—;X2 consists of S or O;L2 consists of a bond or alkylene;R3 consists of alkylene; andR4 and R5 are the same or different, each consisting of alkyl; or a pharmaceutical preparation thereof.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention concerns bioactive renal cell populations, renal cell constructs, and methods of making and using the same.
Thu, 25 Aug 2016 08:00:00 EDTEmbodiments of the invention provide at least one polymer covalently conjugated to an esterase. The at least one polymer includes a plurality of oxime functional groups.
Thu, 25 Aug 2016 08:00:00 EDTDisclosed are compositions comprising mutant chondroitinase ABC I and methods of their use. Compositions comprising either the nucleic acid or amino acid sequence of mutant chondroitinase ABC I are disclose. Specifically, compositions comprising the nucleic acid sequence of SEQ ID NO:2 or the amino acid sequence of SEQ ID NO:6 are disclosed. The mutant chondroitinase ABC I compositions can be used to treat cancer, increase oncolytic virus spread or treat central nervous system injury.
Thu, 25 Aug 2016 08:00:00 EDTProvided is a method for purifying α-thrombin and for quantifying α-thrombin and its degradation polypeptides in a liquid proteinatious solution. The method employs a one-step anion exchange chromatography method. The method allows purification and/or quantification of a homogenous post-translationally modified α-thrombin. The method can also be used for purification and/or quantification of β-thrombin.
Thu, 25 Aug 2016 08:00:00 EDTThe invention relates to the cloning, sequencing and characterization of the gene responsible for Quorum Quenching (QQ) activity against Quorum Sensing (QS) signals of the Tenacibaculum sp. strain 20J (CECT7426). Said gene encodes a peptide having at least lactonase activity with a percentage of identity less than 38% with the lactonases described up until now for other species, as well as the sequences of the homologous genes present in other species of the genus Tenacibaculum. Said peptide shows a broad spectrum of activity degrading optionally substituted N-acyl-homoserine lactones (AHLs) of 4-14 carbon atoms in the side chain thereof, is active at pH comprised between 3 and 9, proteinase K- and chymotrypsin-resistant and does not interact with β-lactam antibiotics.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention provides a method of purifying highly pure retinal pigment epithelial cells from a cell population obtained by induction of differentiation of pluripotent stem cells into retinal pigment epithelial cells, by a simple and easy operation in a short period. The purification method of the present invention includes a step of introducing a cell population containing retinal pigment epithelial cells obtained by differentiation induction of pluripotent stem cells on laminin or a fragment thereof on a filter, and obtaining a cell population that passed the filter.
Thu, 25 Aug 2016 08:00:00 EDTMethods for generating human arterial endothelial cells under defined conditions in the absence of insulin are described.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to a method to reprogramming pluripotent stem cells (PSCs) by epigenetic conditioning and metabolic reprogramming into p PSCs with highly controllable biological functions, the cells obtained by said method as well as methods of using said cells.
Thu, 25 Aug 2016 08:00:00 EDTThe present disclosure provides fragrance and flavor compositions as well as products incorporating such compositions. The disclosed compositions can include (6Z)-non-6-enenitrile of formula (I) and one or more additional fragrance and/or flavor components. The fragrance and flavor compositions of the present disclosure can have appealing, fresh, natural cucumber, melon, and/or violet profiles.
Thu, 25 Aug 2016 08:00:00 EDTMethods and systems are provided for producing ionized alkaline solutions (e.g. ionized alkaline water) that exhibit long-term stability when stored at room temperature.
Thu, 25 Aug 2016 08:00:00 EDTA composition comprising an ethylene (meth)acrylic acid copolymer and an anti-fouling agent is provided. The composition selectively disintegrates in media of different ionic strengths. Also provided is a method of preventing fouling using the composition.
Thu, 25 Aug 2016 08:00:00 EDTDisclosed is a small molecule dye for use in imaging in the near-infrared window, namely between 1000 nm-1700 nm wavelength. The present dyes are also useful for photoacoustic imaging and photothermal therapy. The dyes have a structure of a D-A-D (donor-acceptor-donor) fluorescent compound core and side chains rendering the compounds water soluble and easily conjugated to hydrophilic polymers and/or targeting ligands. Further disclosed is compound, CH1055 that can be PEGylated, conjugated to a targeting ligand, or conjugated to taurine. Key steps utilized to assemble the core structure of the target included a cross-Suzuki coupling reaction, iron reduction and N-thionylaniline induced ring closure. Four carboxylic acid groups were introduced into the donor-acceptor-donor (D-A-D) type fluorescent compound to impart a certain aqueous solubility and to allow facile conjugation to targeting ligands.
Thu, 25 Aug 2016 08:00:00 EDTThe present disclosure relates to a process for making a branched copolymer comprising reacting polymer monomers with macro-azo polyethylene glycol (PEG) initiators and cross-linkers, in the presence of a chain transfer agent, wherein said process comprises the step of traditional radical polymerization. The process further comprises a step of dialysis to obtain polymer nano-particles. The process further comprises the step of loading the polymer nanoparticles with a hydrophobic compound. The present disclosure also relates to the use of the polymer nanoparticles for the slow release of a hydrophobic compound in a neutral or alkaline environment or the fast release of a hydrophobic compound in an acidic environment.
Thu, 25 Aug 2016 08:00:00 EDTThe present disclosure provides a binding protein comprising: a polypeptide heavy chain comprising: VH1—(X1)n-VH2—CH (X2)y wherein VH1 is a first variable domain, VH2 is a second variable domain, CH is a constant domain, X1 represents an amino acid or peptide, X2 represents an Fc region, n is 0 or 1 and y is independently 1 or 2, and a polypeptide light chain comprising: VL1-(X1)n-VL2-C wherein VL1 is a first variable domain, VL2 is a second variable domain, C is a constant domain, X1 represents an amino acid or peptide and n is 0 or 1, wherein the heavy chain and light chain are aligned such that VH1 and VL1 form a first binding domain, and VH2 and VL2 form a second binding domain and wherein: there is a disulfide bond between VH1 and VL1, and/or there is a disulfide bond between VH2 and VL2, and use thereof in treatment.
Thu, 25 Aug 2016 08:00:00 EDTThe preset invention provides a method of increasing the effect of an activated-potentiated form of an antibody to an endogenous biological molecule by combining said endogenous biological molecule with an activated-potentiated form of an antibody to endothelial NO-synthase. The present invention also provides a pharmaceutical composition comprising a) an activated-potentiated form of an antibody to an endogenous biological molecule, and b) an activated-potentiated form of an antibody to NO synthase.
Thu, 25 Aug 2016 08:00:00 EDTIt is intended to disclose an antibody which binds to DLL3 protein. Preferably, the antibody of the present invention recognizes a region from amino acids 216 to 492 in human DLL3 having the amino acid sequence as set forth in SEQ ID NO: 1. The present invention also provides a pharmaceutical composition, for example, an anticancer agent, comprising the antibody of the present invention as an active ingredient. The present invention further discloses a method for diagnosing cancer using the antibody of the present invention and a diagnostic drug for cancer comprising the antibody of the present invention.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to an antibody, recombinant or synthetic antigen-binding fragments thereof able to recognise and bind an epitope comprised in the TrkA amino acid sequence, medical uses thereof and a pharmaceutical composition comprising at least one of the above antibody, recombinant or synthetic antigen-binding fragments thereof.
Thu, 25 Aug 2016 08:00:00 EDTThere is disclosed compositions and methods relating to or derived from anti-CD137 antibodies. More specifically, there is disclosed fully human antibodies that bind CD137, CD137-antibody binding fragments and derivatives of such antibodies, and CD137-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease requiring either stimulation of immune responses or suppression. Diseases amenable to treatment is selected from the group consisting of cancers, autoimmune diseases and viral infections.
Thu, 25 Aug 2016 08:00:00 EDTThe invention provides dual specific anti-FGFR2 and FGFR3 (FGFR2/3) antibodies, and compositions comprising and methods of using these antibodies.
Thu, 25 Aug 2016 08:00:00 EDTAgonists to ICOS in combination with a blocking agent to a T cell inhibitory receptor (e.g., CTLA-4, PD-1, etc.) are demonstrated herein to be useful for the treatment of tumors.
Thu, 25 Aug 2016 08:00:00 EDTThe present disclosure is related to improved methods for use of a humanized binding polypeptide specific for the alpha beta T cell receptor (αβ-TCR). In particular, this disclosure relates to improved methods of use of a humanized anti-αβ-TCR antibody, which is derived from the murine monoclonal antibody BMA031, in immunosuppressive therapy. Novel methods using humanized monoclonal antibodies and/or humanized monoclonal antibody fragments (e.g., anti-αβTCR antibodies and/or fragments thereof) are also provided. Novel methods using repetitive administration of humanized monoclonal antibodies and/or humanized monoclonal antibody fragments (e.g., anti-αβTCR antibodies and/or fragments thereof) to reduce αβ T cells in the subject relative to γδ cells in the subject are provided.
Thu, 25 Aug 2016 08:00:00 EDTThe invention relates to the field of molecular medicine. In particular, it relates to compositions and methods to enhance the clearance of aberrant cells, e.g. cancer cells or virus-infected cells, by the host's immune system. Provided is a composition comprising (i) a therapeutic compound that can trigger a host's immune effector cells against an aberrant cell, such as a therapeutic antibody, and (ii) at least one agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPalpha.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention is directed to anti-PVRIG antibodies and methods of using same.
Thu, 25 Aug 2016 08:00:00 EDTProteins that bind IL-17 and TNF-α are described along with their use in compositions and methods for treating psoriatic arthritis.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to antibodies and antigen-binding portions thereof that specifically bind to a M-CSF, preferably human M-CSF, and that function to inhibit a M-CSF. The invention also relates to human anti-M-CSF antibodies and antigen-binding portions thereof. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins derived from human anti-M-CSF antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-M-CSF antibodies, compositions comprising these antibodies and methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-M-CSF antibodies. The invention also relates to transgenic animals and transgenic plants comprising nucleic acid molecules of the present invention.
Thu, 25 Aug 2016 08:00:00 EDTIt is possible to inhibit inflammatory processes by administration of antibodies to chemokines. Identification of chemokines which are over-produced makes it possible to block specific chemokine activity using antibodies to the over-expressed chemokines.
Thu, 25 Aug 2016 08:00:00 EDTProvided is a T cell activation inhibitor containing an RGM inhibiting substance such as an anti-RGM neutralizing antibody and the like as an active ingredient. The T cell activation inhibitor is useful as a pharmaceutical composition for the prophylaxis or treatment of autoimmune diseases such as multiple sclerosis and the like, and other diseases caused by T cell activation. In addition, a T cell activation inhibiting substance can be screened for by contacting a test substance with RGM and selecting a test substance that lowers the activity level of RGM.
Thu, 25 Aug 2016 08:00:00 EDTEculizumab, a humanized monoclonal antibody against C5 that inhibits terminal complement activation, showed activity in a preliminary 12-week open-label trial in a small cohort of patients with paroxysmal nocturnal hemoglobinuria (PNH). The present study examined whether chronic eculizumab therapy could reduce intravascular hemolysis, stabilize hemoglobin levels, reduce transfusion requirements, and improve quality of life in a double-blind, randomized, placebo-controlled, multi-center global Phase III trial. It has been found that eculizumab stabilized hemoglobin levels, decreased the need for transfusions, and improved quality of life in PNH patients via reduced intravascular hemolysis. Chronic eculizumab treatment appears to be a safe and effective therapy for PNH.
Thu, 25 Aug 2016 08:00:00 EDTProvided are human alpha-synuclein-specific autoantibodies as well as fragments, derivatives and variants thereof as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for α-synuclein are also disclosed. The antibody, immunoglobulin chain(s), as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for α-synuclein targeted immunotherapy and diagnosis, respectively.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention provides novel methods and compositions comprising highly specific and highly effective antibodies that specifically recognize and bind to specific epitopes from a range of β-amyloid proteins. The antibodies of the present invention are particularly useful for the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system.
Thu, 25 Aug 2016 08:00:00 EDTA method of inhibiting complement activation mediated by C3b inhibitors in a subject includes administering a C3B inhibitor to the subject to inhibit at least one of C3b binding to factors B and properdin, inhibit C3 cleavage, inhibit the activation of neutrophils, monocytes, platelets, and endothelium; or inhibit the formation of C3a, C5a, and MAC.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to a new and improved method for preparing a highly concentrated immunoglobulin composition from pooled plasma for subcutaneous injection. A composition comprising 20% or more immunoglobulin suitable for subcutaneous use is also described.
Thu, 25 Aug 2016 08:00:00 EDTThe invention refers to a cross-neutralizing antibody comprising at least one polyspecific binding site that binds to alpha-toxin (Hla) and at least one of the bi-component toxins of Staphylococcus aureus, which antibody comprises at least three complementarity determining regions (CDR1 to CDR3) of the antibody heavy chain variable region (VH), wherein A) the antibody comprises a) a CDR1 comprising or consisting of the amino acid sequence YSISSGMGWG (SEQ ID 1); and b) a CDR2 comprising or consisting of the amino acid sequence SIDQRGSTYYNPSLKS (SEQ ID 2); and c) a CDR3 comprising or consisting of the amino acid sequence ARDAGHGVDMDV (SEQ ID 3); or B) the antibody comprises at least one functionally active CDR variant of a) the parent CDR1 consisting of the amino acid sequence of SEQ ID 1; or b) the parent CDR2 consisting of the amino acid sequence of SEQ ID 2; or c) the parent CDR3 consisting of the amino acid sequence of SEQ ID 3; wherein the functionally active CDR variant comprises at least one point mutation in the parent CDR sequence, and comprises or consists of the amino acid sequence that has at least 60% sequence identity with the parent CDR sequence. It further refers to such cross-neutralizing antibody which is a functionally active variant antibody of a parent antibody that comprises a polyspecific binding site of the VH amino acid sequence of SEQ ID 20, and the VL amino acid sequence of SEQ ID 39, which functionally active variant antibody comprises at least one point mutation in any of the framework regions (FR) or constant domains, or complementarity determining regions (CDR1 to CDR6) in any of SEQ ID 20 or SEQ 39, and has an affinity to bind each of the toxins with a Kd of less than 10−8M, preferably less than 10−9M.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates, in general, to HIV-1-reactive antibodies and, in at least certain specific embodiments, to broadly neutralizing antibodies (bnAbs) (and fragments and derivatives thereof) and to compositions comprising same. The invention further relates to methods of using such bnAbs (and fragments and derivatives thereof) and compositions in immunotherapy regimens (e.g., passive immunotherapy regimens). The antibodies (and fragments and derivatives thereof) disclosed herein can also be used in methods of identifying candidate immunogens for use in inducing an immune response against HIV-1 in a mammal (e.g., a human). The invention also relates to such methods and to immunogens so identified.
Thu, 25 Aug 2016 08:00:00 EDTProvided herein are peptides that exhibit ApoE biological activity, as well as compositions and pharmaceutical formulations that include the peptides. The peptides, compositions, and methods disclosed herein have broad applications as they can be used to treat a broad spectrum of injury, diseases, disorders, and clinical indications.
Thu, 25 Aug 2016 08:00:00 EDTFormulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided including a pre-lyophilized formulation, a reconstituted lyophilized formulation, and a stable liquid formulation. Preferably, the fusion protein has the sequence of SEQ ID NO:4.
Thu, 25 Aug 2016 08:00:00 EDTDisclosed herein are IL-4 cytokine compositions with enhanced biological activity having increased selectivity for IL-4 cytokine receptors, and methods for their use. These compositions encompass interleukin-4 (IL-4) muteins. The disclosed methods encompass administering an IL-4 to treat neoplastic diseases, autoimmune diseases, infectious diseases or for expanding a hematopoietic cell population.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention relates to HCBI (Healthy Cattle Blood Isolate) nucleotide sequences as well as probes and primers comprising part of said nucleotide sequences and antibodies against polypeptides encoded by said nucleotide sequences. Said compounds are useful as early markers for the future development of cancer and diseases of the CNS.
Thu, 25 Aug 2016 08:00:00 EDTThe present invention provides new protease resistant polypeptides, as well as compositions and methods for treating, ameliorating or preventing conditions related to joint damage, including acute joint injury and arthritis.