Abstract: The present invention relates to flavour generation. In particular the invention relates to a method for flavour generation in a heat-treated food product using a prolidase enzyme. The invention also relates to a heat-treated food product prepared according to the method of the invention.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: The present invention relates to flavour generation. In particular the invention relates to a method for flavour generation in a heat-treated food product using a prolidase enzyme. The invention also relates to a heat-treated food product prepared according to the method of the invention.

Abstract: The present invention discloses formulation of a serum-free medium used for human pluripotent stem cells, which comprises the following raw materials: inorganic salt components, organic components, amino acids and amino acid salts, energy substances and metabolic intermediates, vitamins and antioxidants, proteins and polypeptides, trace elements and chromogenic substances; while the culture process comprises the following steps: selecting a basic formulation, performing combination screening, identifying and evaluating results, and testing a new formulation of culture; and proportioning according to the following methods: adding aforesaid raw materials into 950 ml of water for injection, stirring gently until dissolved, and finally adding 2.438 g of sodium bicarbonate, and stirring gently until dissolved, and then adding 1 liter of water for injection, adjusting the pH to the desired value with 1 mol/L sodium hydroxide solution or 1 mol/L hydrochloric acid solution, finally filtering sterilized with 0.

Abstract: The present invention provides an adjuvant that can cause immune activation or particularly T cell immune activation. The present invention provides an adjuvant that can cause particularly antigen-specific immune activation or particularly T cell immune activation.

Abstract: The disclosure is directed to an isolated polynucleotide encoding a modified picornavirus 3C protease, wherein the modified picornavirus 3C protease includes an altered secondary structure and one or more amino acid substitution(s) located at one or more amino acid position(s) corresponding to positions 16-25, 99-100 and 115-130 of a wild-type Fool-and-Mouth Disease Virus (FMDV) 3C protease, wherein the isolated polynucleotide encoding the modified picornavirus 3C protease, when transformed into and co-expressed in a host cell, enhances transgene expression of a P1 precursor polypeptide in comparison to an amount of P1 precursor polypeptide transgene expression exhibited in a host cell transformed and co-expressed with a control picornavirus 3C protease, wherein the one or more corresponding amino acid position(s) is/are identified by an alignment of the modified picornavirus 3C protease with the one or more of the wild type FMDV 3C protease(s).

Abstract: The present invention pertains to a cell culture medium comprising copper as a media supplement, which was shown to control recombinant protein glycosylation and methods of using thereof. The present invention further pertains to a method of controlling or manipulating glycosylation of a recombinant protein of interest in a large scale cell culture.

Abstract: The present invention relates to protease variants and methods for obtaining protease variants. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

Abstract: The present invention relates to an isolated chimeric molecule comprising a degradation domain including a eukaryotic U-box motif and a targeting domain capable of immunospecifically directing the degradation domain to a substrate where the targeting domain is heterologous to the degradation domain. A linker couples the degradation domain to the targeting domain. Also disclosed are compositions as well as methods of treating a disease, substrate silencing, screening agents for therapeutic efficacy against a disease, and methods of screening for disease biomarkers.

Abstract: Provided concerns a blood biomarker for discerning the cerebral deposition of amyloid beta, which is a causative material of Alzheimer's dementia. A marker according to the subject matter can conveniently and rapidly predictive of cerebral amyloid beta accumulation by use of a blood and can be effectively used in diagnosing relevant diseases including mild cognitive impairment at a preclinical level.

Abstract: Disclosed herein is an expression system for the production and secretion of biologically active clot-specific streptokinase (CSSK) protein in methylotrophic yeast. Yeast-expressed CSSK protein displays improved plasminogen activation and fibrin selectivity. Further disclosed are methylotrophic yeast transformed with at least one copy of functional cDNA sequence encoding CSSK adjunct with modified signal sequence which results in secretion of mature and correctly processed CSSK.

Abstract: The present invention relates to nucleic acid expression cassettes and vectors containing liver-specific regulatory elements and codon-optimized factor IX or factor VIII transgenes, methods employing these expression cassettes and vectors and uses thereof. The present invention is particularly useful for applications using liver-directed gene therapy, in particular for the treatment of hemophilia A and B.

Abstract: The methods of harvesting cells are provided, wherein the methods comprise introducing a processing material and a source material into a processing loop. The processing loop comprises a processing chamber and a filtering device. The processing material and the source material are circulating through the processing chamber and the filtering device, wherein the processing chamber has a mass; balancing an influx of the processing material into the processing chamber with a permeate flux of the filtering device to maintain the mass of the processing chamber at a constant value; and collecting the cells in a collection chamber. Cell harvesting devices are also provided for processing and harvesting cells using a control law to balance the mass of the processing chamber through the entire process.

Abstract: The present invention relates to polynucleotides comprising a Factor IX nucleotide sequence, wherein the Factor IX nucleotide sequence comprises a coding sequence that encodes a Factor IX protein or fragment thereof and wherein a portion of the coding sequence is not wild type. The present invention further relates to viral particles comprising a recombinant genome comprising the polynucleotide of the invention, compositions comprising the polynucleotides or viral particles, and methods and uses of the polynucleotides, viral particles or compositions.

Abstract: The present invention relates to isolated polypeptides having protease activity, and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Abstract: A liquid or dried granulated milk clotting aspartic protease enzyme composition and process for isolating a milk clotting aspartic protease enzyme of interest.

Abstract: This invention relates to collagen-binding synthetic peptidoglycans and engineered collagen matrices comprising a collagen matrix and a collagen-binding synthetic peptidoglycan where the collagen-binding synthetic peptidoglycan can be aberrant or can have amino acid homology with a portion of the amino acid sequence of a protein or a proteoglycan that regulates collagen fibrillogenesis. The invention also relates to kits, compounds, compositions, and engineered graft constructs comprising such collagen-binding synthetic peptidoglycans or engineered collagen matrices and methods for their preparation and use.

Abstract: Disclosed are methods and compositions for treatment of a subject having a biliary disorder. The methods include administering a therapeutically effective amount of a serine protease inhibitor to a subject in need thereof. The biliary disorder include biliary atresia, a biliopathy, Primary Biliary Cirrhosis (PBC), Primary Sclerosing Cholangitis (PSC), and combinations thereof. In certain aspects, the serine protease inhibitor may be a protease inhibitor rC1 Inhibitor.

Abstract: The present invention relates to expression cassettes and vectors comprising Alzheimer's disease-related genes and a cell line transformed by the disclosed expression cassettes and vectors, and more specifically, the expression cassettes according to the present invention comprise amyloid precursor protein (APP), Tau protein, and presenilin-1 (PS1) genes associated with Alzheimer's disease so that mutant genes thereof can be simultaneously expressed. Additionally, the present invention relates to a cell line transformed by the disclosed expression cassettes or vectors comprising APP, Tau protein, and PS1 genes, and further, to an animal model transformed by the vectors or cell line.

Abstract: Compositions and methods useful for the treatment of neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD) are disclosed.

Abstract: An isolated and purified peptide, neonatal NET-inhibitory Factor (nNIF), is disclosed. Methods for treatment of and prophylaxis against inflammatory disorders are also disclosed, including methods of treatment of and prophylaxis against inflammatory disorders comprising administering NET-inhibitory peptides (NIPs), which may be a nNIF, a pharmaceutically acceptable salt of a nNIF, a nNIF analog, a pharmaceutically acceptable salt of a nNIF analog, a nNIF-Related Peptide (nNRP), including the nNRP, Cancer-Associated SCM-Recognition, Immune Defense Suppression, and Serine Protease Protection Peptide (CRISPP), a pharmaceutically acceptable salt of a nNRP, a nNRP analog, or a pharmaceutically acceptable salt of a nNRP analog, to an individual.

Abstract: The present invention relates to a pharmaceutical composition for treating cerebrovascular diseases including stem cell-derived exosomes as an active ingredient. The stem cell-derived exosomes according to the present invention have superior nerve cell protective effects, such as inhibition of cerebral ventricular distention, reduction of hydrocephalus, and inhibition of nerve cell death and cellular inflammation in an intraventricular hemorrhage (IVH) animal model, and thus, can be useful in treating cerebrovascular diseases including intraventricular hemorrhage, etc.

Abstract: Genetically modified rodents such as mice and rats, and methods and compositions for making and using the same, are provided. The rodents comprise a humanization of at least one endogenous rodent Tmprss gene, such as an endogenous rodent Tmprss2, Tmprss4, or Tmprss11d gene.

Abstract: Genetically modified rodents such as mice and rats, and methods and compositions for making and using the same, are provided. The rodents comprise a humanization of at least one endogenous rodent Tmprss gene, such as an endogenous rodent Tmprss2, Tmprss4, or Tmprss11d gene.

Abstract: The present invention relates to: a composition for dissolving thrombi comprising a peptide comprising the Arg-Gly-Asp motif; a pharmaceutical composition for treating stenotic or occlusive vascular diseases which comprises the same; and a thrombus dissolving method and a method for treating stenotic or occlusive vascular diseases, comprising the step of administering the same. The compositions and methods of the present invention have the advantage that they effectively break down already formed thrombi by adopting the principle of targeting integrin within the thrombus such as platelet surface GPIIb-IIIa, which is not the same as the existing principle of plasminogen activation. Also, the compositions and methods of the present invention have a nerve-protecting function as they effectively open as far as the microvasculature, without the occurrence of restenosis after penetration.

Abstract: Disclosed are a modified FIX (factor IX) polypeptide comprising a leucine, cysteine, aspartic acid, glutamic acid, histidine, lysine, asparagine, glutamine or tyrosine in position 338; pharmaceutical preparations containing said modified FIX polypeptide; a nucleotide sequence coding for the modified FIX polypeptide; and a method for producing the modified FIX polypeptide.

Abstract: The invention relates to the field of medicinal research, cartilage physiology and diseases involving the degeneration of cartilage tissue. More specifically, the invention relates to methods and means for identifying compounds that inhibit catabolic processes in chondrocytes and that decrease the degradation of cartilage and/or ECM. The invention also relates to the compounds that are useful in the treatment of osteoarthritis. The invention also relates to targets, the modulation of which results in a decrease in the degradation of ECM and/or cartilage and decrease inflammation. In addition, the invention relates to compositions and methods for the use thereof in treating conditions that are characterized by the degradation of ECM and/or cartilage and inflammation.

Abstract: Modulation of the ADAMTS1 signaling pathway alters the commitment of progenitor cells to a muscle fate; and increases muscle mass.

Abstract: This invention relates to molecules, particularly polypeptides, more particularly fusion proteins that include a serpin polypeptide or an amino acid sequence that is derived from a serpin and second polypeptide comprising of at least one the following: an Fc polypeptide or an amino acid sequence that is derived from an Fc polypeptide; a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide; a WAP domain containing polypeptide or a sequence derived from a WAP containing polypeptide; and an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing and purifying such molecules.

Abstract: Embodiments of the present invention relate to a buffer composition for an integrated nucleic acid amplification and hybridization reaction. The buffer comprise about 50-200 mM of a salt, about 10-30 mM Tris-HCl, about 2-10M Water soluble magnesium salt, about 0.05-1.5% surfactant, about 0.05-0.15 mg/ml stabilizing protein about 50-300 nM of one or more primers, about 20-150 uM of one or more dNTPs, about 5-15% glycerine, about 0.5-1.5% formamide and at least about 5 unit/ml polymerase.

Abstract: Screening assays and methods of using same for screening to identify modulator agents or compounds that affect matrix metalloproteinase-2 (MMP-2) mediated activation of toll-like receptor-2 (TLR-2) are described herein. Pharmaceutical and immunogenic compositions comprising agents or compounds that modulate MMP-2 mediated activation of TLR-2 are also encompassed. Methods for modulating MMP-2 mediated activation of TLR-2 using MMP-2 peptides in pharmaceutical and immunogenic compositions, as well as vaccines, are also envisioned. Melanoma is an exemplary tumor type that expresses MMP-2 and for which such pharmaceutical and immunogenic compositions, as well as vaccines, would confer benefit to patients. Also encompassed are methods for reducing MMP-2 mediated activation of TLR-2 and downstream signaling therefrom so as to achieve more effective T cell responses to MMP-2 expressing tumors.

Abstract: A novel method of treating and preventing bacterial diseases is provided. In particular, the present invention relates to compositions and methods for inhibition of Gram negative, Gram positive and acid fast bacilli in general and tuberculosis (TB), mycobacterium avium complex (MAC), and anthrax in particular. Thus, the invention relates to modulation of cellular activities, including macrophage activity, and the like. More particularly, the present invention relates to the inhibitory compounds comprising naturally occurring and man-made inhibitors of serine protease.

Abstract: The present invention relates to mutated tissue plasminogen activators, and their use for treating thrombotic diseases.

Abstract: Disclosed herein are methods relating to inhibiting or reducing proliferation of a cancer cell, for treating cancer in a subject in need of treatment, predicting the risk of progression of cancer to a more aggressive cancer, and screening for cancer in a subject, that comprise detecting and/or decreasing the levels of SUMO conjugated proteins and detecting and/or interfering with SUMO conjugation.

Abstract: Anti-TACE (ADAM17) antibodies are disclosed that for the first time in the art are capable of binding to TACE, of acting as antagonists of one or more its biological activities, in particular by binding to TACE in a cross domain binding mode in which residues in both the catalytic domain and in the cysteine rich/disintegrin domains (Dis-Cys) are involved in antibody binding to TACE, helping to improve the specificity of the antibody binding and/or helping to improve inhibition of TACE biological activity. The therapeutic uses of the antibodies, in particular for the treatment of cancer are disclosed.

Abstract: The present invention discloses novel hybrid proteins that have both plasminogen activator and anti-thrombotic properties, including clot specific action, that renders these as highly advantageous for the treatment of circulatory disorders involving fibrin clot formation due to underlying tissue damage in the blood vessels leading to myocardial infarction, strokes etc. Also disclosed are new proteins, and methods of obtaining the same, that help to dissolve blood clots by activating plasminogen in a plasmin or thrombin dependent manner and also inhibit both the activity and generation of thrombin through the intrinsic pathway of blood coagulation.

Abstract: The present invention includes compositions and methods for making and using a vaccine that includes a DC-specific antibody or fragment thereof to which an engineered Gag antigen is attached to form an antibody-antigen complex, wherein the Gag antigen is less susceptible to proteolytic degradation by eliminating one or more proteolytic sites or a DC-specific antibody or fragment thereof to which an engineered Nef antigen is attached to form an antibody-antigen complex, wherein the Nef antigen comprises one or more codon usage optimization that increase antibody-antigen complex secretion, or both, wherein the vaccine is able to elicit an HIV-specific T cell immune response to Gag p17, Gag p24, Nef and/or Cyclin D1.

Abstract: Described herein are compositions which include digestive enzymes and which are formulated to reduce one or more symptoms of a neuropsychiatric disorder. Also described herein is a method for treating an individual with a neuropsychiatric disorder using digestive enzymes and their derivatives to alleviate the symptoms of neuropsychiatric disorders. The method comprises administering to the individual an effective amount of digestive enzymes that are either naturally or recombinantly derived, or their derivatives, in an amount effective to reduce one or more symptoms of the neuropsychiatric disorder.

Abstract: The invention relates to a polypeptide having chymosin activity which: a. is capable of hydrolysing bovine alpha s1-casein at position F23F24 so as to form ?s1-I CN (f24-199) more rapidly than camel chymosin; and b. has a C/P ratio higher than the C/P ratio of bovine chymosin.

Abstract: The present invention provides pregnancy associated plasma protein A2 (PAPP-A2), its nucleotide and amino acid sequences, antisense molecules to the nucleotide sequences which encode PAPP-A2, expression vectors for the production of purified PAPP-A2, antibodies capable of binding specifically to PAPP-A2, hybridization probes or oligonucleotides for the detection of PAPP-A2-encoding nucleotide sequences, genetically engineered host cells for the expression of PAPP-A2, and methods for screening for pathologies in pregnant and non-pregnant patients. Methods for screening for altered focal proliferation states in pregnant and/or non-pregnant patients, which include detecting levels of PAPP-A2, are also described.

Abstract: The present invention provides a method of expressing at least one heterologous nucleic acid sequence in a cell, the method comprising introducing at least one heterologous nucleic acid sequence into a cell by infecting said cell with a recombinant negative-strand RNA virus vector comprising said at least one heterologous nucleic acid sequence, wherein the recombinant negative-strand RNA virus vector includes a viral genome coding for a mutated P protein, which leads to a loss of the viral genome replication ability without a loss of the viral transcription ability, and wherein said at least one heterologous nucleic acid sequence encodes a cellular reprogramming or programming factor or a therapeutic protein. In addition, the present invention provides a cell or a population of cells prepared in vitro by said method as well as a pharmaceutical composition comprising said cell or population of cells.

Abstract: The present invention discloses a thrombolytic therapy for acute myocardial infarction by t-PA. A chimeric truncated form of t-PA is designed and expressed in Pichia pastoris. The new variant t-PA comprises of a finger domain of Desmoteplase, an epidermal growth factor (EGF) domain, a kringle 1 domain, a kringle 2 domain in which the lysine binging site is deleted, and a protease domain where the four amino acids lysine 296, arginine 298, arginine 299, and arginine 304 are substituted by aspartic acid. The chimeric t-PA shows has increased activity of 14 fold in presence of fibrin. The t-PA shows 10-fold increased potency than commercially available full length t-PA (Actylase®) and provides 1.2 fold greater affinity to fibrin. Further a residual activity of only 68% is observed after incubation of Actylase® with PAI-1 and 91% residual activity for t-PA. The t-PA variant is acceptable plasminogen activator with enhanced biochemical properties.

Abstract: Provided herein are methods for purifying recombinant A Disintegrin-like and Metallopeptidase with Thrombospondin Type 1 Motif 13 (ADAMTS13) protein from a sample. The method comprises enriching for ADAMTS13 protein by chromatographically contacting the sample with hydroxyapatite under conditions that allow ADAMTS13 protein to appear in the eluate or supernatant from the hydroxylapatite. The methods may further comprise tandem chromatography with a mixed mode cation exchange/hydrophobic interaction resin that binds ADAMTS13 protein. Additional optional steps involve ultrafiltration/diafiltration, anion exchange chromatography, cation exchange chromatography, and viral inactivation. Also provided herein are methods for inactivating virus contaminants in protein samples, where the protein is immobilized on a support. Also provided herein are compositions of ADAMTS13 prepared according to said methods.

Abstract: The present invention provides pregnancy associated plasma protein A2 (PAPP-A2), its nucleotide and amino acid sequences, antisense molecules to the nucleotide sequences which encode PAPP-A2, expression vectors for the production of purified PAPP-A2, antibodies capable of binding specifically to PAPP-A2, hybridization probes or oligonucleotides for the detection of PAPP-A2-encoding nucleotide sequences, genetically engineered host cells for the expression of PAPP-A2, and methods for screening for pathologies in pregnant and non-pregnant patients. Methods for screening for altered focal proliferation states in pregnant and/or non-pregnant patients, which include detecting levels of PAPP-A2, are also described.

Abstract: Methods and dosage formulations are provided for subcutaneous administration in which therapeutic agents are modified to increase the hydrophilicity and molecular dimensions in relation to the native state of the therapeutic agent, in which the Cmax:Caverage ratio is lower than the Cmax:Caverage ratio of the agent when delivered intravenously.

Abstract: Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotropin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.

Abstract: The present invention is related to novel mammalian enterokinase analogues such as mammalian enterokinase light chain analogues and methods of making such. Also described herein is a method for cleaving proteins having an enterokinase cleavage site.

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Abstract: Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and/or cell culture supernatant with a low ammonium (NH4+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.

Abstract: Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I.