Abstract: This invention provides biomarkers whose concentrations in blood plasma are associated with the presence or absence of PAD in the patient from whom the plasma sample is taken. The invention also provides biomarkers for distinguishing between PAD patients who are long claudicators and PAD patients who are not. In addition, the invention provides methods for identifying additional biomarkers, methods for detecting the biomarkers in patients, and methods for identifying agents, including pharmaceutical agents, which interact with the biomarkers and are useful for preventing or treating PAD in patients.

Abstract: This invention is related to preparation of photosensitive ruthenium based aminoacid monomers and oligomers, aminoacid monomer-protein cross-linking using photo sensitat ion and conjugation on micro and nano-structures by ruthenium-chelate based monomers. Its vast range biotechnolgy applications of multifunctional, biocompatible, stabilE and specific micro and nanobio-conjugates, which will stand-alone or simultaneously enable (i) both purification and determination, (ii) both targeting and imaging and theranostics and (iii) catalysis and determination. The construction and method of preparation is applicable to silica materials, superparamagnetic particles, QDs, CNTs, Ag/Au nanoparticles and Au surfaces and polymeric materials. The photosensitive aminoacid monomer linkers can react via chemically and biocompatible to a lot of different micro and nano-surface and then to the protein when they act as a single-step cross-linking reaction using irradiation.

Abstract: The present invention relates to a method for increasing the expression of a protein in cells, preferably in eukaryotic cells, by reducing the number of RNase L cleavage sites in the coding and/or non-coding region of the nucleic acid sequence of said protein. Furthermore, it relates to nucleic acid sequences exhibiting a reduced number of RNase L cleavage sites as well as to the proteins translated from such sequences.

Abstract: Several aspects of this invention relate to diagnosis of diabetic states in a mammal using protein isoforms. In some aspects, it relates to a method for determining the diabetic state of a mammal. This method can include, for example, (a) measuring the serum concentration of one or more protein isoforms, (b) analyzing the serum concentration of the one or more protein isoforms, and (c) determining the diabetic state of the mammal. Other aspects include kits used to perform the method. Further aspects are the isolated protein isoforms themselves, and their methods of isolation.

Abstract: Neuromedin U receptor agonists for use in the treatment of metabolic disorders such as obesity and diabetes are disclosed. In particular, disclosed are neuromedin U receptor agonists that comprise neuromedin S (NMS).

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The present invention provides novel methods for reducing the serine protease and/or serine protease zymogen content of a plasma-derived protein composition. Also provided are methods for manufacturing plasma-derived protein compositions having reduced serine protease and\or serine protease zymogen content. Among yet other aspects, the present invention provides aqueous and lyophilized compositions of plasma-derived proteins having reduced serine protease and/or serine protease zymogen content. Yet other aspects include methods for treating, managing, and/or preventing a disease comprising the administration of a plasma-derived protein composition having a reduced serine protease or serine protease zymogen content.

Abstract: The invention is directed to the use of cpn10 in transplantation and particularly to treatment and/or prevention of graft versus host disease. The invention provides a method of administration of cpn10 to a donor and/or recipient animal or cells, tissues or organs derived from the donor, although in a particularly advantageous form treatment of both the donor and recipient animal. The method may further include the administration to the donor and/or recipient animal at least one other immunosuppressive agent to prevent or alleviate graft versus host disease.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention provides a method for the treatment of a subject suffering from a cardiovascular disease using a therapeutically effective amount of at least one enzyme that is capable of inhibiting PAI-1 activity. The invention also provides a method of decreasing the risk of the occurrence of a cardiovascular disease in a subject who presents at least one risk factor that is associated with a cardiovascular disease, by administering to the subject a therapeutically effective amount of at least one enzyme that is capable of inhibiting PAI-1 activity. Additionally, the invention provides a method of inhibiting PAI-1 activity in a subject in need thereof, where the subject is administered an enzyme selected from a protease or peptidase.

Abstract: Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair damaged tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to an ischemia-associated molecule; and (b) an activator domain that that detectably modulates the activity of a cellular network.

Abstract: The present invention relates to compositions comprising alpha 1-antitrypsin linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in the treatment of alpha 1-antitrypsin-related diseases, disorders, and conditions.

Abstract: The present application relates to methods for growing crystals of both the uncomplexed and complexed forms of ?-secretase (BACE) polypeptide. The present application also relates to crystalline forms of uncomplexed BACE and the three-dimensional structure of BACE, as determined from the crystals. In addition, the present application relates to the use of crystalline forms of BACE to identify ligands, preferably inhibitors (antagonists), which bind to, and preferably inhibit the enzymatic activity of, BACE. Furthermore, the present application relates to nucleic acid sequences encoding BACE polypeptide, and methods for making BACE in greater quantity than prior methods, resulting in more effective crystallization.

Abstract: A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8.

Abstract: The present invention relates to a method for producing a mature von Willebrand Factor (VWF) from von Willebrand Factor pro-peptide comprising the steps: immobilizing VWF pro-peptide on an ion exchange resin, incubating the immobilized VWF pro-peptide with furin to obtain immobilized mature VWF, and isolating mature VWF from the ion exchange resin by elution.

Abstract: This disclosure relates to erythropoietin (EPO) fusion polypeptides; nucleic acid molecules encoding said polypeptides and methods of treatment that use said polypeptides.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule having at least a portion of the B domain intact, which is conjugated to a water-soluble polymer such as polyethylene glycol having a molecular weight of greater than 10,000 Daltons. The construct has a biological activity of at least 80% of the biological activity of native Factor VIII, and the in vivo half-life of the construct is increased by at least 1.5 fold as compared to the in vivo half-life of native factor FVIII.

Abstract: The invention provides vitamin K-dependent polypeptides with enhanced membrane binding affinity. These polypeptides can be used to modulate clot formation in mammals. Methods of modulating clot formation in mammals are also described.

Abstract: Provided are a pharmaceutical composition for prevention and treatment of a neural disease including at least one selected from the group consisting of mesenchymal stem cells (MSCs), a culture solution of the MSCs, activin A, PF4, decorin, galectin 3, GDF15, glypican 3, MFRP, ICAM5, IGFBP7, PDGF-AA, SPARCL1, thrombospondin-1, WISP1, progranulin, IL-4, a factor inducing expression thereof, and any combination thereof, and a method therefor.

Abstract: A process for cross-linking proteins, according to which the crosslinking agent is dihydroxyacetone and the proteins are chosen from proteins from animal tissues, from milk or from blood, such as in particular casein, gelatin or collagen; proteins from cereals, such as in particular maize, wheat or rice proteins; protein from high-protein plants, such as in particular pea, alfalfa, lupin, barley, millet or sorghum proteins; proteins from oleaginous plants, such as in particular soybean proteins, for instance soybean cakes, rapeseed or flax proteins, for instance rapeseed cakes, sunflower, groundnut or cotton proteins; and proteins from tubers, such as in particular from potato or manioc.

Abstract: The present invention relates to the use of C-reactive protein, its mutants, metabolites and polypeptides and related compounds thereof for the treatment of various disease states and conditions associated with systemic lupus erythematosus (SLE), including lupus of the skin (discoid), systemic lupus of the joints, lungs and kidneys, hematological conditions including hemolytic anemia and low lymphocyte counts, lymphadenopathy and CNS effects including memory loss, seizures and psychosis, among numerous others as otherwise disclosed herein, hi another aspect of the invention, the reduction in the likelihood that a patient who is at risk for an outbreak of a disease state or condition with systemic lupus erythematosus will have an outbreak is an additional aspect of the present invention.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The present invention generally provides processes for purification of Inter-alpha inhibitor proteins (I?Ip) and compositions thereof from blood.

Abstract: A novel medicament for ameliorating neurotransmission dysfunction diseases is provided. A medicament for ameliorating neurotransmission dysfunction diseases comprising as a main active ingredient preferably a selenocysteine-containing protein such as Selenoprotein P or a selenocysteine-containing peptide that consists of said protein or a series of said peptides. A medicament suited for ameliorating neurotransmission dysfunction diseases caused by various pathological conditions is provided.

Abstract: The invention provides a composition containing particulate composite of a polymer and a therapeutic agent. The composition also contains a complexing agent. The polymer interacts with the complexing agent in a host-guest or a guest-host interaction to form an inclusion complex. A therapeutic composition of the invention may be used to deliver the therapeutic agent and to treat various disorders. Both the polymer of the particulate composite and the complexing agent may be used to introduce functionality into the therapeutic composition. The invention also relates to a method of preparing a composition. The method combines a therapeutic agent, a polymer having host or guest functionality, and a complexing agent having guest or host functionality to form the therapeutic composition. The complexing agent forms an inclusion complex with the polymer. The invention also relates to a method of delivering a therapeutic agent.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, particularly ovarian cancer, are disclosed. Illustrative compositions comprise one or more ovarian tumor polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly ovarian cancer.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The present invention describes the design and development of new fibrinogen and fibrinogen derived products with significantly reduced binding to bacteria while retaining normal physiological functions by using modified fibrinogen amino acid sequences. The present invention describes modified sequences of Fg ?-chains and ?-chains with reduced binding to S. aureus ClfA and S. epidermidis SdrG respectively. Modified Fg with the described modifications will not bind other bacterial surface proteins that bind Fg using similar mechanisms as ClfA and SdrG. These new Fg and Fg derived products will therefore have less binding to bacteria and will be advantageous compared to normal human Fg in a number of different settings.

Abstract: Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract: The present invention relates to the use of FIXa and FVIII in the preparation of a composition for the treatment of haemophilia A or haemophilia B in a subject which does not present with anti-FVIII antibodies. The present invention further relates to a composition comprising FIXa and a composition comprising FVIII for simultaneous, simultaneous separate or sequential use in the treatment of haemophilia A or haemophilia B in a subject which does not present with anti-FVIII antibodies.

Abstract: The invention provides processes for preparing a cell-binding agent chemically coupled to a drug. A first process comprises covalently attaching a linker to a cell-binding agent, an optional purification step, conjugating a drug to the cell-binding agent, a subsequent purification step, and optional holding steps. A second process comprises covalently attaching a linker to a cell-binding agent, a purification step, conjugating a drug to the cell-binding agent, a subsequent purification step, holding steps, and optionally a tangential flow filtration (TFF) step.

Abstract: The instant invention provides novel and effective methods of isolating alpha-1-antitrypsin from cryo-poor plasma and formulating it into therapeutic products. This invention achieves higher yields and a superior quality of alpha-1-antitrypsin. Alpha-1-antitrypsin is isolated from cryo-poor plasma, using one or more salts selected from a group comprising sodium citrate, sodium acetate, sodium gluconate, ammonium sulfate, sodium chloride, sodium sulfate and ammonium chloride in two fractionation steps, followed by diafiltration to remove those salts employed.

Abstract: The invention is directed to biomarkers for determining the EGFR kinase activity in a subject, and the use thereof for predicting and monitoring therapeutic intervention in cancer patients. Areas of application are the life sciences: biology, biochemistry, biotechnology, medicine and medical technology. The biomarkers are selected from a first group consisting of Amy 1, Apo Al, Carbx, Casp, AFP, ApoM, SAP, Fib-a, Fib-b, Fib-g, ApoE, A2MG, A2MG isoform, Serpin, Clusterin, MHC-fB, SAP isoform, or from a second group consisting of Gpx3, properidin, MUP1, HMW-K, Lifr-p, Orm 1, MBL-A, MBP-C, wherein the biomarkers are regulated by EGF overexpression in a subject.

Abstract: The present invention provides fusion peptides having GLP-1 activity and enhanced stability in vivo, in particular resistancy to dipeptidyl peptidase IV. The fusion peptide comprises as component (I) N-terminally a GLP-1(7-35, 7-36 or 7-37) sequence and as component (II) C-terminally a peptide sequence of at least 9 amino acids or a functional fragment, variant or derivative thereof. Component (II) is preferably a full or partial version of IP2 (intervening peptide 2). A preferred embodiment comprises the sequence GLP-1(7-35, 36 or 37)/IP2/GLP-1(7-35, 36 or 37) or GLP-2. The fusion peptide may be produced in engineered cells or synthetically and may be used for the preparation of a medicament for treating various diseases or disorders, e.g. diabetes type 1 or 2, apoptosis related diseases or neurodegenerative disorders.

Abstract: A method for precipitating casein from a suspension comprising milk is disclosed. The method includes the following steps: adding a phosphate solution to a suspension; mixing the phosphate solution with the suspension to form a mixture having a phosphate concentration greater or equal to 40 mM; freezing the mixture having a phosphate concentration greater or equal to 40 mM to obtain a frozen mixture; and thawing the frozen mixture to obtain casein-containing aggregates in the mixture, in which the phosphate solution is buffered at a pH value of no less than 4.4.

Abstract: The present invention provides methods and non-fluorescent carbocyanine quencher compounds having the general formula: Wherein the A moiety is a substituted pyridinium, unsubstituted pyridinium, substituted quinolinium, unsubstituted quinolinium, substituted benzazolium, unsubstituted benzazolium, substituted indolinium, or substituted indolinium. The invention further provides luminescent donor molecule-quencher pairs and luminescent donor molecule-quencher-luminescent acceptor molecule conjugates wherein the quencher is a cyanine compound of the present invention. The energy transfer pairs are used to detect an analyte of interest in a sample.

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

Abstract: The invention relates to vWF cleaving entities having a molecular weight of 180 kD, 170 kD, 160 kD, 120 kD or 110 kD and an N-terminal amino acid sequence of AAGGILHLELLV, vWF cleaving complexes and methods for their production.

Abstract: Novel human p53 splice variant displaying differential transcriptional activity Described is a nucleic acid molecule encoding a p53 variant characterized in that it is capable of transactivating the p21- and 14-3-3?-promoter but not the mdm2-, bax- and PIG3-promoter. Preferably, in said p53 variant exon 7, exon 8 and/or exon 9 are partially or entirely deleted. Finally, means for inhibiting the activity of this p53 variant are described which are useful for the therapy of cancer.

Abstract: The present invention relates to methods for glycosylating a protein in which the protein is modified to include an alkyne and/or an azide group. The invention further relates to a protein glycosylated by these methods.

Abstract: The present disclosure relates to a clottable concentrate of platelet growth factors for therapeutic and/or cosmetic use, preferably comprising the growth factors PDGF, TGT-?, IGF, EGF, CTGF, bFGF and VEGF. In a preferred embodiment, the clottable concentrate of platelet growth factors does not induce blood cell-related transfusion reactions. The present disclosure also relates to a method for preparing a clottable concentrate of platelet growth factors including the steps of contacting a platelet concentrate with a solvent and/or a detergent, incubating the platelet concentrate with the solvent and/or detergent for a period of at least 5 minutes to 6 hours, at a pH maintained in a range from about 6.0 to about 9.0, and at a temperature within the range of from 2° C. to 50° C., preferably within the range of from 25° C. to 45° C., and removing the solvent and/or the detergent by oil extraction and/or chromatographic means.

Abstract: The present invention provides a method for providing alpha-1 antitrypsin (?1-AT) to a subject, in particular a method for treating or preventing a disorder or disease associated with ?1-AT deficiency in the subject, wherein the method comprises providing, subcutaneously, a therapeutically or prophylactically effective amount of ?1-AT to the subject. Also provided is a composition and article of manufacture comprising ?1-AT, in particular a formulation suitable for subcutaneous administration of ?1-AT.

Abstract: This invention provides an isolated nucleic acid molecule which encodes immunoglobulin receptor, Immunoglobulin superfamily Receptor Translocation Associated, IRTA, protein. Provided too, are the IRTA proteins encoded by the isolated nucleic acid molecules, IRTA1, IRTA2, IRTA3, IRTA4 or IRTA5 proteins, having the amino acid sequences set forth in any of FIG. 18A, 18B-1-18B-3, 18C-1-18C-2, 18D-1-18D-2 or 18E-1-18E-2. Oligonucleotides of the isolated nucleic acid molecules are provided. Antibodies directed to an epitope of a purified IRTA1, IRTA2, IRTA3, IRTA4 or IRTA5 proteins are also provided, as are pharmaceutical compositions comprising such antibodies or oligonucleotides. Methods for detecting a B cell malignancy in a sample from a subject; diagnosing B cell malignancy in a sample from a subject; detecting human IRTA protein in a sample; and treating a subject having a B cell cancer are also provided.

Abstract: The invention relates to a method for separating fibronectin from plasma fractions by adjusting a pH value of less than 5.4 such that fibronectin is precipitated and extracted from the solution.

Abstract: The present invention concerns a monoclonal antibody and corresponding hybridoma cells and antigens suitable for isolating fetal cells from maternal blood. The monoclonal antibody reacts with a surface antigen present on fetal red blood cells including their nucleated precursor cells, but not with surface antigens on adult erythroid cell.