Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract: A method is disclosed for using tenecteplase to restore function in dysfunctional hemodialysis catheters, which have a blood flow rate of less than 300 mL/minute. Kits are also provided with instructions to direct the user to administer tenecteplase in a total dose of about 3 to 4 mg locally into all catheter lumens and allow the tenecteplase to dwell in the catheter for from about one hour to about 72 hours.

Abstract: The invention relates to a recombinant human factor IX (FIX) characterized in that said factor is obtained by a preparation method comprising, or even consisting of, the steps which consist in causing the genetic material encoding the FIX to be expressed in vitro in a human hepatocyte cell line Huh7, recovering the cellular supernatant in which the FIX was secreted and, optionally, purifying the synthesized FIX.

Abstract: The present invention relates to targeted killing of a cell utilizing a chimeric polypeptide comprising a cell-specific targeting moiety and a signal transduction pathway factor. In a preferred embodiment, the signal transduction pathway factor is an apoptosis-inducing factor, such as granzyme B, granzyme A, or Bax.

Abstract: The present invention relates to a disintegrin and metalloproteinase containing thrombospondin 1-like domains (ADAMTS) and in particular to a novel ADAMTS13 protease and to nucleic acids encoding ADAMTS13 proteases. The present invention encompasses both native and recombinant wild-type forms of ADAMTS13, as well as mutant and variant forms including fragments, some of which posses altered characteristics relative to the wild-type ADAMTS13. The present invention also relates to methods of using ADAMTS13, including for treatment of TTP. The present invention also relates to methods for screening for the presence of TTP. The present invention further relates to methods for developing anticoagulant drugs based upon ADAMTS13.

Abstract: Human MARK genes are identified as modulators of the PTEN pathway, and thus are therapeutic targets for disorders associated with defective PTEN function. Methods for identifying modulators of PTEN, comprising screening for agents that modulate the activity of MARK are provided.

Abstract: The present invention relates to polypeptides comprising protease variants of wild type human neprilysin having an altered specificity and/or activity. In particular the present invention relates to polypeptides comprising protease variants derived from human neprilysin having an increased specificity and/or activity against certain substrates, in particular against amyloid beta.

Abstract: A Factor X (hereinafter referred to as “FX”) with a high activity is provided. The present invention relates to a method for efficiently preparing a recombinant, two-chain FX which comprises intervening glycosylation at such an amino acid sequence that is essential for glycosylation in FX to thereby allow for expression of a recombinant FX with no glycosylation, and the recombinant FX with no glycosylation obtained by said method.

Abstract: The present invention provides a method for producing a desired protein (such as a desired heterologous protein) comprising: (a) providing a host cell comprising a first recombinant gene encoding a protein comprising the sequence of a first chaperone protein, a second recombinant gene encoding a protein comprising the sequence of a second chaperone protein and a third gene, such as a third recombinant gene, encoding a desired protein (such as a desired heterologous protein), wherein the first and second chaperones are different; and (b) culturing the host cell in a culture medium to obtain expression of the first, second and third genes.

Abstract: Methods for producing proteins and glycoproteins in Pichia pastoris that lack detectable cross binding activity to antibodies made against host cell antigens are described. In particular, methods are described wherein recombinant Pichia pastoris strains that do not display a ?-mannosyltransferase 2 activity with respect to an N-glycan or O-glycan and do not display at least one activity selected from a ?-mannosyltransferase 1, 3, and 4 activity to produce recombinant proteins and glycoproteins. These recombinant Pichia pastoris strains can produce proteins and glycoproteins that lack detectable ?-mannosidase resistant ?-mannose residues thereon and thus, lack cross binding activity to antibodies against host cell antigens. Further described are methods for producing bi-sialylated human erythropoietin in Pichia pastoris that lack detectable cross binding activity to antibodies against host cell antigens.

Abstract: The present invention relates to the modification process of bovine embryonic stem cells and purification process of proteins generated by modified stem cells. In particular, the present invention lies in the field of medicine and veterinary.

Abstract: Elevated levels of cathepsin E (catE) are demonstrated to be diagnostic of intestinal forms of cancer, such as colorectal cancer. Elevated levels of cathepsin E (catE, monomeric forms) are demonstrated to be detectable in the urine of animals having colorectal cancer, and a diagnostic/screening method for identifying and/or detecting colorectal cancer in an animal from a urine sample is provided. Specific tissue immunohistochemcial staining for catE (monomeric forms) in dysplastic tissue is also disclosed, and is shown to correlate with the level of dysplastic lesion severity. Hence, a method for identifying and determining the level of dysplastic lesion severity is provided. Cathepsin E mRNA transcription and expression levels are also demonstrated to be upregulated in dysplastic tissue, relative to non-dysplastic tissue. Hence, a method for transcriptionally profiling an animal to monitor the progression of colorectal disease is provided.

Abstract: The present invention relates to metalloprotease enzymes isolated from scorpion venom, their nucleic acid and amino acid sequences, and methods of use thereof in the treatment of various diseases, disorders and cosmetic conditions.

Abstract: This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

Abstract: Provided are an aptamer bound to chymase to inhibit activity of chymase; an aptamer containing a nucleotide sequence represented by X1GAUAGAN1N2UAAX2 wherein X1 and X2 are the same or different and each is A or G, and N1 and N2 are the same or different and each is A, G, C, U or T; a complex containing the aptamer and a functional substance (e.g., affinity substance, labeling substance, enzyme, drug delivery medium, drug and the like); a pharmaceutical or a reagent containing the aptamer or complex; a detection and a purification methods of chymase using the aptamer or complex and the like.

Abstract: The present invention discloses an improved process for the production of desired recombinant peptides from bacterial cells by using G-CSF as a novel fusion partner for their high level expression in these cells. The invention further provides an expression system comprising the fusion protein wherein the G-CSF is operatively linked to the peptide of interest via an enzymatic or chemical cleavage site which can be used to separate the fusion partner from the said peptide.

Abstract: The present invention relates to a host cell comprising a cofilin-specific small interfering RNA (siRNA) sequence. The host cell may further comprise a nucleic acid encoding a recombinant protein. The present invention also relates to a method for producing a recombinant protein by the host cell comprising a cofilin-specific small interfering RNA (siRNA) sequence.

Abstract: The present invention provides novel polynucleotides encoding PCSK9b and PCSK9c polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel PCSK9b and PCSK9c polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

Abstract: An affinity substrate for the selective binding of a protein of blood plasma includes a solid substrate material on which are immobilized deoxyribonucleic aptamers specifically binding with the plasma protein.

Abstract: The invention relates to unglycosylated folded C-terminal fragments of a multidomain serine protease of the complement cascade obtainable by expression in a bacterial host, wherein said serine protease is capable of binding a recognition molecule of the complement cascade, e.g. C1 or MBL. The invention also relates to methods and bacterial expression vectors for the preparation of said fragments, uses of said fragments for raising antibodies and screening substrates or inhibitors of said serine proteases and uses of the fragments in research and treatment of complement related disorders. The invention also relates to assay methods for assessing MASP-1 and MASP-2 levels in a sample of biological origin. The invention provides for research tools, assays and diagnostic kits useful in complement research and research and diagnosis of complement related disorders.

Abstract: Methods for detecting cancer as well as methods of diagnosis of cancer by detecting proteins secreted into biological fluids are disclosed The invention was first applied to detecting proteins secreted into serum and urine However, it is understood that the methods have broader application to developing tools and systems for detecting proteins secreted into other biological fluids such as, but not limited to, saliva, spinal fluid, seminal fluid, vaginal fluid, and ocular fluid Reliable detection of proteins secreted into biological fluids provided by embodiments of the methods will enable more timely and accurate detection and diagnosis of cancer.

Abstract: The invention provides isolated nucleic acids encoding a variety of proteins having diagnostic, preventive, therapeutic, and other uses. These nucleic and proteins are useful for diagnosis, prevention, and therapy of a number of human and other animal disorders. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies. Diagnostic, screening, and therapeutic methods using compositions of the invention are also provided. The nucleic acids and polypeptides of the present invention are useful as modulating agents in regulating a variety of cellular processes.

Abstract: A nucleic acid includes at least 15 nucleotides with a length specifically binding with the human factor VII/VIIa.

Abstract: An affinity substrate for selectively binding a coagulation protein, includes a substrate solid on which nucleic aptamers binding specifically to the coagulation protein are immobilized.

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: The present invention relates to a drug delivery system for use in the treatment of vascular and vessel-related pathologies, comprising a drug delivery platform that comprises at least one compound capable of exerting an effect on the formation and/or maintenance of a thrombus in the vessel to be treated. The platform is preferably formed by liposomes that are sterically stabilized by grafting of poly(ethylene glycol) onto the liposome surface. The liposomes may further comprise photosensitizers and targeting molecules. The liposomes may be thermosensitive. The compound is suitably tranexamic acid. The drug delivery system is preferably used for the treatment of port wine stains.

Abstract: Lower eukaryotic cells such as Pichia pastoris that normally cannot use galactose as a carbon source but which have been genetically engineered according to the methods herein to use galactose as a sole source of carbon are described. The cells are genetically engineered to express several of the enzymes comprising the Leloir pathway. In particular, the cells are genetically engineered to express a galactokinase, a UDP-galactose-C4-epimerase, and a galactose-1-phosphate uridyltransferase, and optionally a galactose permease. In addition, a method is provided for improving the yield of glycoproteins that have galactose-terminated or -containing N-glycans in cells that have been genetically engineered to produce glycoproteins with N-glycans having galactose residues but which normally lack the enzymes comprising the Leloir pathway comprising transforming the cells with one or more nucleic acid molecules encoding a galactokinase, a UDP-galactose-C4-epimerase, and a galactose-1-phosphate uridyltransferase.

Abstract: Tau protein has a causative role in Alzheimer's disease and multiple other neurodegenerative disorders exhibiting tau histopathology collectively termed tauopathies. The primary function of tau protein is to facilitate assembly and maintenance of microtubules in neuronal axons. In the disease process tau protein becomes modified, loses its affinity to microtubules and accumulates in the cell body where it forms aggregates. The large neurofibrillary tangles formed from tau protein assembled into filaments were thought to be the pathological structure of tau. However, more recent work indicates that smaller, soluble oligomeric forms of tau are best associated with neuron loss and memory impairment. A novel and unexpected protease activity has been discovered to be associated with tau in oligomeric but not monomeric structures. Methods have been developed to form and purify tau protease and to assay its activity.

Abstract: The present invention relates to the use of at least one protease for the manufacture of a medicament for the treatment and/or prevention of ocular diseases related to neoangiogenesis selected from the group consisting of age related macular degeneration (AMD), choroidal neovascularisation, Hippel-Lindau Disease, iris neovascularisation, ischemic proliferative retinopathy, neovascularisation of the Cornea, and proliferative sickle cell retinopathy, wherein the at least one protease is selected from the group consisting of plant, non-mammalian animal and microbial proteases.

Abstract: A gene or protein set includes at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, and possibly 40, 45, 50, 55, 60, 65 genes or proteins, antibodies or hypervariable portion thereof directed against the proteins encoded by these genes.

Abstract: Intra-arterial administering at least one blood coagulation to a bleeding patient is provided, together with a pharmaceutical composition therefor.

Abstract: The invention pertains to the use and production of non-neurotoxic plasminogen activating factors e.g. of Desmodus rotundus (DSPA) for the therapeutic treatment of stroke in humans in order to provide a new therapeutic concept for treating stroke in humans.

Abstract: A method for distinguishing prostate cancer from prostatic hypertrophy using the method for analyzing PSA and an analysis kit of PSA are provided. An object of the present invention can be solved by being brought into contact a lectin having an affinity for ?-N-acetylgalactosamine residues and/or a lectin having an affinity for fucose ?(1, 2) galactose residues with a sample possibly containing PSA, to determine an amount of PSA having an affinity for the lectin. A method for distinguishing prostate cancer from prostatic hypertrophy can be provided by this method.

Abstract: The present invention provides the enzyme and enzymatic procedures for cleaving the ? secretase cleavage site of the APP protein and associated nucleic acids, peptides, vectors, cells and cell isolates and assays. The invention further provides a modified APP protein and associated nucleic acids, peptides, vectors, cells, and cell isolates, and assays that are particularly useful for identifying candidate therapeutics for treatment or prevention of Alzheimer's disease.

Abstract: The invention relates to the purification of different gamma carboxylated forms of a polypeptide using ion exchange chromatography. In particular, the invention provides a method for purifying a polypeptide having a desired content of gamma-carboxyglutamic acid from a sample comprising mixture of species of said polypeptide having different contents of gamma-carboxyglutamic acid, said method comprising the steps of: (a) loading said sample onto an anion exchange chromatography material; (b) eluting said polypeptide using a solution at a pH of less than pH 9.0 comprising at least one salt selected from ammonium acetate, ammonium chloride and sodium acetate; and (c) selecting a fraction obtained from said elution wherein the polypeptides in the fraction have the desired content of gamma-carboxyglutamic acids.

Abstract: A thrombin-like enzyme isolated from Agkistrodon acutus venom, comprising an alpha subunit having the sequence of SEQ ID No. 1 and a beta subunit having the sequence of SEQ ID No. 2, which are linked by seven disulfide bonds, is provided. The hemocoagulase of Agkistrodon acutus in the present invention is a serine proteinase having a molecular weight of 29.3-29.5 kD and an isoelectric point of 5.5, and is able to hydrolyze the alpha chain of human fibrinogen. The invention also provides methods of purifying the thrombin-like enzyme from snake venom, which comprise removing insoluble substance by pretreatment, conducting twice of anion-exchange column chromatography, collecting active eluting peak, dialyzing, ultra-filtrating and desalinating so as to obtain a snake venom thrombin-like enzyme; and the enzyme has a specific activity of no less than 180 u/mg protein, a HPLC purity of more than 95% and a yield of 0.7%-0.8% based on the weight of the snake venom raw material.

Abstract: The present invention provides methods of detecting cancer using biomarkers.

Abstract: The present invention provides an improved coating for surfaces of medical implants. The coating comprises at least one interfacial biomaterial (IFBM) which is comprised of at least one binding module that binds to the surface of an implant or implant-related material (“implant module”) and at least one binding module that selectively binds to a target analyte or that is designed to have a desired effect (“analyte module”). The modules are connected by a linker. In some embodiments, the IFBM coating acts to promote the recognition and attachment of target analytes to surface of the device. The IFBM coating improves the performance of implanted medical devices, for example, by promoting osteointegration of the implant.

Abstract: The present invention provides a method of increasing cathepsin B-induced cleavage of amyloid-? (A?) peptide in a cell or tissue, the method generally involving contacting the cell or tissue with an agent that increases the level of cathepsin B in the cell or tissue. The present invention further provides variant cathepsin B polypeptides that are resistant to inhibition by a cysteine protease inhibitor; as well as nucleic acids encoding the variants, and host cells comprising the nucleic acids.

Abstract: Compositions which specifically block cathepsin L function in podocytes, compositions which protect cytoskeletal adaptor protein (CD2AP) for degradation, compositions which modulate expression or function of cytoskeletal adaptor protein (CD2AP), protect against renal diseases or disorders. Methods of treatment in vivo involve use of one or more compositions.

Abstract: Polypeptides which are related to the neprilysin enzyme family and have zinc metalloprotease activities and are referred to as IGS5, polynucleotides encoding such polypeptides, vectors containing such polynucleotides, host cells containing such vectors, processes for producing such polypeptides and/or polynucleotides, screening methods for identifying compounds which stimulate or inhibit IGS5 polypeptides and/or polynucleotides, and the use of such polypeptides and/or polynucleotides in therapy of various dysfunctions, disorders or diseases, particularly cardiovascular diseases, metabolic diseases such as diabetes mellitus type II, and neurodegenerative disorders, such as Parkinson's Disease.

Abstract: Disclosed are novel enteropeptidase polypeptides, polynucleotides encoding the polypeptides, nucleotide constructs, vectors, host cells comprising the polynucleotides, and methods for producing the polypeptides and polynucleotides. Such polypeptides are useful as protein engineering tool for enzymatic cleavage of fusion proteins. Also provided are kits comprising the polypeptides of the invention.

Abstract: The present invention relates generally to the fields of molecular biology and growth factor regulation. More specifically, the invention concerns modulators of hepatocyte growth factor activator function, and the identification and uses of said modulators.

Abstract: The invention relates to therapeutic fusion proteins in which a coagulation factor is fused to a half-life enhancing polypeptide, and in which both are connected by a linker peptide that is proteolytically cleavable. The cleavage of such linkers liberates the coagulation factor from activity-compromising steric hindrance caused by the half-life enhancing polypeptide and thereby allows the generation of fusion proteins may show relatively high molar specific activity when tested in coagulation-related assays. Furthermore, the fact that the linker is cleavable can enhance the rates of inactivation and/or elimination after proteolytic cleavage of the peptide linker compared to the rates measured for corresponding therapeutic fusion proteins linked by the non-cleavable linker having the amino acid sequence GGGGGGV.

Abstract: The invention is directed to isolated genomic polynucleotide fragments that encode human carboxypeptidase D, vectors and hosts containing the fragment and fragments hybridizing to noncoding regions as well as antisense oligonucleotides to these fragments. The invention is further directed to methods of using these fragments to obtain human Carboxypeptidase D and to diagnose, treat, prevent and/or ameliorate a pathological disorder.

Abstract: The present invention is directed towards the co-crystal structure of Factor D and an anti-Factor D antibody or an antigen binding fragment thereof.

Abstract: Modified factors VII/VIIa with a high stability, nucleic acids encoding such modified factors VII/VIIa, and methods of preparing the same.

Abstract: Biomarkers that correlate to treatment with drugs that inhibit c-met are disclosed. These biomarkers have been shown to have utility in assessing response to the compounds. The expression level of the biomarkers is reduced upon treatment with c-met inhibitor compounds, thus indicating that these biomarkers are involved in c-met activity.

Abstract: Disclosed are compositions for activating thrombin precursors to thrombin. The compositions provided include polypeptide compositions wherein the pre-pro-sequence comprises a thrombin cleavage site. The compositions provided also include polynucleotides encoding said polypeptides and recombinant systems for expressing said polypeptides. This disclosure also relates to methods for producing said compositions, recovering said compositions, activating said compositions purifying said compositions and producing active thrombin molecules using the active form of said compositions.

Abstract: The invention provides compositions including modified blood clotting factors that have a non-native proteolytic cleavage site engineered into them allowing intracellular cleavage and secretion of an active form. The compositions are useful in the methods for treating a bleeding or clotting disorder.