Urokinase Patents (Class 435/215)
  • Patent number: 9645157
    Abstract: The invention concerns a marker for low-grade inflammation and metabolic syndrome (MS) and MS-related diseases and/or low-grade inflammation-related diseases such as cardiovascular disease, ischemic heart disease and type 2 diabetes. More particularly it concerns the measurement of the concentration of soluble urokinase plasminogen activator receptor (suPAR) in human biological fluids (sputum, cystic fluid, ascites, serum, plasma, urine) as a tool of diagnosing and/or prognosticating low-grade inflammation and metabolic syndrome and the risk of development of the related diseases such as cancer, cardiovascular disease, ischemic heart disease and type 2 diabetes.
    Type: Grant
    Filed: June 23, 2014
    Date of Patent: May 9, 2017
    Assignee: Hvidovre Hospital
    Inventors: Jesper Eugen-Olsen, Steen B. Haugaard, Ove Andersen
  • Publication number: 20150079633
    Abstract: The present invention relates to lower eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar and sugar nucleotide transporters to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified lipid-linked oligosaccharides are created or selected. N-glycans made in the engineered host cells exhibit GnTIV, GnTV, GnT VI or GnTIX activity, which produce multiantennary N-glycan structures and may be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar, sugar nucleotide transporters, to yield human-like glycoproteins. For the production of therapeutic proteins, this method may be adapted to engineer cell lines in which any desired glycosylation structure may be obtained.
    Type: Application
    Filed: July 25, 2014
    Publication date: March 19, 2015
    Inventors: Piotr Bobrowicz, Stephen R. Hamilton, Tillman U. Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Robert C. Davidson
  • Patent number: 8968728
    Abstract: New thrombolytic protein molecules such as recombinant staphylokinase or streptokinase, urokinase, tissue plasminogen activator and the like, and suitable variants thereof, for targeting to brain tissue or any other tissue by either fusing to, or by synthesizing the candidate thrombolytic molecule(s) with a protein sequence comprising a strong amphipathic alpha helix containing protein transduction domain. Thrombolytic protein molecule(s) so engineered with the protein transduction domain is useful for enhanced uptake of such protein thrombolytic molecule(s) across the cell membranes and tissues including the blood brain barrier and find their use in the treatment of vascular thrombosis including cerebrovascular disorders caused by cerebral thrombosis or cerebral haemorrhage when used a as a therapeutic. The design and processes for cloning, expression, purification and protein transduction of such proteins across cell membranes.
    Type: Grant
    Filed: May 11, 2007
    Date of Patent: March 3, 2015
    Assignee: Bharat Biotech International Limited
    Inventors: Krishna Murthy Ella, Kandaswamy Sumathy
  • Publication number: 20140356344
    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.
    Type: Application
    Filed: August 20, 2014
    Publication date: December 4, 2014
    Applicant: BioAtla LLC
    Inventors: Jay M. Short, Hwai Wen Chang, Gerhard Frey
  • Publication number: 20140199287
    Abstract: The invention concerns the use and the production of non-neurotoxic plasminogen activating factors, derived, for example, from the common vampire Desmodus rotundus (DSPA), for therapeutic treatment of stroke in humans. The invention provides a novel therapeutic base for treating stroke in humans.
    Type: Application
    Filed: January 9, 2014
    Publication date: July 17, 2014
    Applicant: H. LUNDBECK A/S
    Inventors: Mariola SOHNGEN, Wolfgang SOHNGEN, Wolf-Dieter SCHLEUNING, Robert MEDCALF
  • Patent number: 8603437
    Abstract: The present invention discloses a method for the enzyme-mediated, site-specific, in-vivo precipitation of a water soluble molecule in an animal. The enzyme is either unique to tumor cells, or is produced within a specific site (e.g., tumor) at concentrations that are higher than that in normal tissues. Alternatively, the enzyme is conjugated to a targeting moiety such as an antibody or a receptor-binding molecule.
    Type: Grant
    Filed: April 30, 2012
    Date of Patent: December 10, 2013
    Assignee: President and Fellows of Harvard College
    Inventors: Amin I. Kassis, Ravi S. Harapanhalli
  • Publication number: 20130324593
    Abstract: The present invention relates to a hybrid promoter, in which a whole or a part of a CMV enhancer, a whole or a part of a ?-actin promoter, a whole or a part of a CMV promoter, and a whole or a part of a ?-actin intron are operably linked to each other, a recombinant vector comprising the same, a transformant transformed with the recombinant vector, a pharmaceutical composition comprising the recombinant vector or the transformant, and a method for preparing a target protein using the recombinant vector or the transformant. The hybrid promoter of the present invention is able to induce high expression of a target protein in a eukaryotic cell. Therefore, the hybrid promoter of the present invention can be effectively used for the development of an antibody or the production of a DNA vaccine.
    Type: Application
    Filed: November 29, 2011
    Publication date: December 5, 2013
    Applicant: LG Life Sciences Ltd
    Inventors: Yeon Chul Kim, Saem Jung, Jun Jung
  • Publication number: 20130039902
    Abstract: The invention concerns the use and the production of non-neurotoxic plasminogen activating factors, derived, for example, from the common vampire Desmodus rotundus (DSPA), for therapeutic treatment of stroke in humans. The invention provides a novel therapeutic base for treating stroke in humans.
    Type: Application
    Filed: February 10, 2012
    Publication date: February 14, 2013
    Applicant: H. Lundbeck A/S
    Inventors: Mariola Sohngen, Wolfgang Sohngen, Wolf-Dieter Schleuning, Robert Medcalf
  • Publication number: 20130034547
    Abstract: A chimeric therapeutic polypeptide of a pre-existing therapeutic polypeptide is disclosed, as are a method of enhancing folded stabilization and a pharmaceutical composition of the glycosylated chimer. The pre-existing and chimeric polypeptides have substantially the same length, substantially the same amino acid residue sequence, and exhibit at least one tight turn containing a sequence of four to about seven amino acid residues in which at least two amino acid side chains extend on the same side of the tight turn and are within less than about 7 ? of each other. The chimeric therapeutic polypeptide has the sequon Aro-(Xxx)n-(Zzz)p-Asn-Yyy-Thr/Ser (SEQ ID NO:001) within that tight turn sequence such that the side chains of the Aro, Asn and Thr/Ser amino acid residues project on the same side of the turn and are within less than about 7 ? of each other. That sequon is absent from the pre-existing therapeutic polypeptide.
    Type: Application
    Filed: August 2, 2012
    Publication date: February 7, 2013
    Inventors: Jeffery W. Kelly, Joshua L. Price, Elizabeth K. Culyba, Evan T. Powers
  • Patent number: 8309341
    Abstract: Compounds of formula (I): wherein: R1 represents a hydrogen atom or a group of formula COR4, or R1 represents a group of formula (A): R2 represents a group of formula NR5R6, or R2 represents a nitrogen-containing heterocyclic group, an aryl group or a heteroaryl group, R3 represents a hydrogen atom or an alkyl group, m represents an integer between 1 and 6 inclusive, n represents 0, 1 or 2, their optical isomers, and also addition salts thereof with a pharmaceutically acceptable acid. Medicinal products containing the same which are useful in treating and/or preventing thrombotic events.
    Type: Grant
    Filed: June 25, 2010
    Date of Patent: November 13, 2012
    Assignees: Les Laboratories Server, L'Institut National des Sciences Appliquées de Rouen, Le Centre National de la Recherche Scientifique, L'Universite de Rouen
    Inventors: Philippe Gloanec, Guillaume De Nanteuil, Jean-Gilles Parmentier, Anne-Françoise Guillouzic, Tony Verbeuren, Alain Rupin, Philippe Mennecier, Marie-Odile Vallez, Jean-Charles Quirion, Philippe Jubault, Nicolas Boyer
  • Patent number: 8304205
    Abstract: The invention relates to methods for determining the activity of a proteolytic coagulation factor of the blood coagulation cascade in a body fluid such as whole blood or plasma. A combination is provided in a reaction mixture. The combination comprises the sample and an activation agent for activating a proteolytic coagulation factor of the blood coagulation cascade or for activating the blood coagulation cascade. The effect of the activating on a reagent system comprising a cleavable moiety is evaluated. The cleavable moiety is or becomes bound to a chemiluminescent agent or a sensitizer agent or both. The chemiluminescent agent and the sensitizer agent are related in that, when in close proximity, energization of the sensitizer agent results in energization of the chemiluminescent agent. The effect of the activating is related to the activity of a proteolytic coagulation factor of the blood coagulation cascade wherein the effect is the extent of cleavage of the cleavable moiety.
    Type: Grant
    Filed: September 29, 2009
    Date of Patent: November 6, 2012
    Assignee: Siemens Healthcare Diagnostics Products GmbH
    Inventors: Andreas Kappel, Andrea Lichte, Norbert Zander, Stefan Teigelkamp, Sabine Teigelkamp, legal representative, Carsten Schelp
  • Publication number: 20120270254
    Abstract: A method for analyzing secretome, a biomarker for lung cancer metastasis, and a siRNA compound for inhibiting lung cancer metastasis are disclosed. The method for analyzing secretome of the present invention comprises the following steps: (A) collecting proteome secreted from a cell; (B) providing a purification gel, wherein the purification gel comprises a low-density layer, and a high-density layer, and the low-density layer is stacked on the high-density layer; (C) adding the proteome on the low-density layer, and separating the proteome through the low-density layer and the high-density layer of the purification gel; (D) collecting the separated proteome on the interface between the low-density layer and high-density layer, and tagging the separated proteome with a reagent after digestion; and (E) analyzing the separated proteome tagged with the reagent, and comparing an analysis result with a proteomic database.
    Type: Application
    Filed: December 27, 2011
    Publication date: October 25, 2012
    Applicant: NATIONAL CHENG KUNG UNIVERSITY
    Inventors: Pao-Chi LIAO, Ying-Hwa CHANG, Kuo-Hsun CHIU, Yu-Shun WU, Shu-Hui LEE
  • Publication number: 20120232007
    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.
    Type: Application
    Filed: October 11, 2010
    Publication date: September 13, 2012
    Applicant: MERCK SHARP & DOHME CORP
    Inventors: Piotr Bobrowicz, Sujatha Gomathinayagam, Stephen Hamilton, Huijuan Li, Natarajan Sethuraman, Terrance A. Stadheim, Stefan Wildt
  • Publication number: 20120231505
    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.
    Type: Application
    Filed: May 17, 2012
    Publication date: September 13, 2012
    Applicant: NOVOZYMES BIOPHARMA DK A/S
    Inventors: Christopher John Arthur Finnis, Darrell Sleep, Gillian Shuttleworth
  • Publication number: 20120231503
    Abstract: The present disclosure relates to a method for producing heterologous protein including: (c) providing a host cell comprising a 2 ?m-family plasmid, the plasmid comprising a gene encoding a protein comprising the sequence of a chaperone protein and a gene encoding a heterologous protein; (d) culturing the host cell in a culture medium under conditions that allow the expression of the gene encoding the chaperone protein and the gene encoding a heterologous protein; (e) purifying the thus expressed heterologous protein from the cultured host cell or the culture medium.
    Type: Application
    Filed: May 17, 2012
    Publication date: September 13, 2012
    Applicant: NOVOZYMES BIOPHARMA DK A/S
    Inventors: Darrell Sleep, Gillian Shuttleworth, Christopher John Arthur Finnis
  • Patent number: 8211428
    Abstract: Methods for identifying modified proteases with modified substrate specificity or other properties are provided. The methods screen candidate and modified proteases by contacting them with a substrate, such as a serpin, an alpha macroglobulins or a p35 family protein or modified serpins and modified p35 family members or modified alpha macroglobulins, that, upon cleavage of the substrate, traps the protease by forming a stable complex. Also provided are modified proteases.
    Type: Grant
    Filed: July 5, 2007
    Date of Patent: July 3, 2012
    Assignees: Torrey Pines Institute for Molecular Studies, Catalyst Biosciences, Inc.
    Inventor: Edwin L. Madison
  • Publication number: 20120164127
    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.
    Type: Application
    Filed: March 9, 2010
    Publication date: June 28, 2012
    Inventors: Jay M. Short, Hwai Wen Chang, Gerhard Frey, Gregory Frost
  • Patent number: 8168159
    Abstract: The present invention discloses a method for the enzyme-mediated, site-specific, in-vivo precipitation of a water soluble molecule in an animal. The enzyme is either unique to tumor cells, or is produced within a specific site (e.g., tumor) at concentrations that are higher than that in normal tissues. Alternatively, the enzyme is conjugated to a targeting moiety such as an antibody or a receptor-binding molecule.
    Type: Grant
    Filed: April 3, 2009
    Date of Patent: May 1, 2012
    Assignee: President and Fellows of Harvard College
    Inventors: Amin I. Kassis, Ravi S. Harapanhalli
  • Publication number: 20120070403
    Abstract: The present invention relates to the use of G-CSF and derivatives thereof for extending the therapeutic window of subsequent thrombolytic treatment of acute stroke, and thereby, allowing the diagnostic examinations which are necessary prior to the thrombolytic treatment in order to avoid hemorrhagic and other severe adverse side effects of the thrombolysis.
    Type: Application
    Filed: February 17, 2010
    Publication date: March 22, 2012
    Applicant: SYGNIS BIOSCIENCE GMBH & CO. KG
    Inventors: Marc Fisher, Armin Schneider
  • Publication number: 20120003695
    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.
    Type: Application
    Filed: February 24, 2010
    Publication date: January 5, 2012
    Inventors: Robert C. Davidson, Piotr Bobrowicz, Dongxing Zha
  • Publication number: 20110091936
    Abstract: The present invention relates generally to glutamine-free cell culture media supplemented with arginine. The invention further concerns the production of recombinant proteins, such as antibodies, in arginine-supplemented glutamine-free mammalian cell culture.
    Type: Application
    Filed: August 6, 2010
    Publication date: April 21, 2011
    Inventors: Martin GAWLITZEK, Shun Luo, Christina Teresa Petraglia
  • Publication number: 20110070607
    Abstract: A chemoenzymatic method for the preparation of a homogeneous glycoprotein or glycopeptide, including (a) providing an acceptor selected from the group consisting of GlcNAc-protein and GlcNAc-peptide; and (b) reacting the acceptor with a donor substrate including an activated oligosaccharide moiety, in the presence of a catalyst comprising endoglycosidase (ENGase), to transfer the oligosaccharide moiety to the acceptor and yield the homogeneous glycoprotein or glycopeptide. The donor substrate includes, in a specific implementation, a synthetic oligosaccharide oxazoline. A related method of glycoprotein or glycopeptide remodeling with a predetermined natural N-glycan or a tailor-made oligosaccharide moiety, and a method of remodeling an antibody including a heterogeneous sugar chain, are also described. The disclosed methodology enables glycoprotein drugs to be modified for prolonged half-life in vivo, reduced immunogenicity, and enhanced in vivo activity, and for targeting and drug delivery.
    Type: Application
    Filed: October 5, 2010
    Publication date: March 24, 2011
    Inventor: Lai-Xi Wang
  • Publication number: 20110053214
    Abstract: The present invention provides a novel lower eukaryotic host cell producing human-like glycoproteins characterized as having a terminal ?-galactose residue and essentially lacking fucose and sialic acid residues. The present invention also provides a method for catalyzing the transfer of a galactose residue from UDP-galactose onto an acceptor substrate in a recombinant lower eukaryotic host cell, which can be used as a therapeutic glycoprotein.
    Type: Application
    Filed: July 21, 2010
    Publication date: March 3, 2011
    Applicant: GLYCOFI, INC.
    Inventors: Robert Collier Davidson, Tillman Ulf Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Piotr Bobrowicz, Stephen Robin Hamilton
  • Publication number: 20110020870
    Abstract: Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways.
    Type: Application
    Filed: October 11, 2010
    Publication date: January 27, 2011
    Applicant: GlycoFi, Inc.
    Inventor: Tillman U. Gerngross
  • Patent number: 7871608
    Abstract: A method of treating a subject, the method including administring a composition that includes a reversibly inactivated acidfied plasmin substantially free of a plasminogen activator, in a low buffering capacity buffer, wherein the composition is a solution suitable for pharmacenutical use that can be raised to physiological pH by adding no more than about 5 volumes of serum to the solution relative to a volume of the solution.
    Type: Grant
    Filed: August 25, 2008
    Date of Patent: January 18, 2011
    Assignee: Talecris Biotherapeutics, Inc.
    Inventors: Thomas P. Zimmerman, Valery Novokhatny, Shan Jiang, James Colandene
  • Patent number: 7837992
    Abstract: A mutant prourokinase plasminogen activator (M5) was developed to make prouPA less subject to spontaneous activation during fibrinolysis. C1-inhibitor complexes with tcM5. The effect of C1-inhibitor on fibrinolysis and fibrinogenolysis by M5 was determined. Supplemental C1-inhibitor restores the stability of M5 but not that of prouPA. Clot lysis by M5 with supplemental C1-inhibitor showed no attenuation of the rate of fibrinolysis, whereas fibrinogenolysis was prevented by C1-inhibitor. Due to higher dose tolerance of M5 with C1-inhibitor, the rate of fibrin-specific lysis reached that achievable by nonspecific fibrinolysis without inhibitor. Plasma C1-inhibitor stabilized M5 in plasma by inhibiting tcM5 and thereby non-specific plasminogen activation. At the same time, fibrin-specific plasminogen activation remained unimpaired. This unusual dissociation of effects has significant implications for improving the safety and efficacy of fibrinolysis.
    Type: Grant
    Filed: April 4, 2007
    Date of Patent: November 23, 2010
    Assignee: Beth Israel Deaconess Medical Center
    Inventors: Victor Gurewich, Ralph Pannell
  • Publication number: 20100254943
    Abstract: The invention provides compositions and methods of identifying, modifying and producing modified target molecules, including therapeutic molecules by modification with non-natural amino acids. Certain aspects of the invention include methods of adding a chemical moiety to a target molecule, and the compositions resulting therefrom. Certain aspects of the invention also relate to kits for identifying, modifying and producing modified target molecules described herein.
    Type: Application
    Filed: November 2, 2009
    Publication date: October 7, 2010
    Applicant: ALLOZYNE, INC.
    Inventors: Kenneth H. Grabstein, Aijun Wang, Natalie Winblade Nairn, Thomas James Graddis, Stephen McCraith, Deepshikha Datta
  • Publication number: 20100184641
    Abstract: Method for increasing half-life of therapeutic agents in plasma and novel polypeptide derivatives.
    Type: Application
    Filed: March 30, 2010
    Publication date: July 22, 2010
    Applicant: Novo Nordisk A/S
    Inventors: Florencio Zaragoza Dorwald, Bernd Peschke
  • Publication number: 20100055762
    Abstract: This invention relates to an agent for promoting differentiation of an ES cell, preferably an agent for promoting differentiation of an ES cell into a hepatocyte or a prophylactic agent for teratoma, comprising uPA. Furthermore this invention relates to a method of promoting differentiation of an ES cell, preferably a method of promoting differentiation of an ES cell into a hepatocyte, comprising the step of contacting uPA with the ES cell, or a method of preparing a hepatocyte comprising the step of contacting uPA with an ES cell to differentiate the ES cell into a hepatocyte.
    Type: Application
    Filed: March 24, 2006
    Publication date: March 4, 2010
    Inventors: Toyohiko Ariga, Taiichiro Seki, Go Watanabe, Hiroto Nakashima, Nobuaki Okumura, Yuichi Hasebe
  • Patent number: 7662582
    Abstract: An efficient method for identifying important cancer biomarkers and identifying progression of bladder cancer using pro-u-PA as a clinical tool is provided. Searching for biomarkers critical for bladder carcinoma diagnosis and prognosis, secreted proteomes of highly malignant U1 and pre-malignant U4 cell lines are first analyzed. Proteins in the cultured media of the U1 and U4 cell-lines were systematically examined by SDS-PAGE combined with MALDI-TOF mass spectrometry. Expression of pro-u-plasminogen activator (pro-u-PA) was confirmed by Western blot analysis and further evaluated. A statistically significant relationship between the low level and absence of pro-u-PA in urine with high stages and grades of the tumor samples was established. Constitutive expression of Ras dominant negative protein led to increased expression of pro-u-PA in cultured media, indicating the loss of pro-u-PA is associated with oncogenic transformation.
    Type: Grant
    Filed: June 24, 2007
    Date of Patent: February 16, 2010
    Assignee: Chang Gung University
    Inventor: Benjamin Yat Ming Yung
  • Publication number: 20100015123
    Abstract: New thrombolytic protein molecules such as recombinant staphylokinase or streptokinase, urokinase, tissue plasminogen activator and the like, and suitable variants thereof, for targeting to brain tissue or any other tissue by either fusing to, or by synthesizing the candidate thrombolytic molecule(s) with a protein sequence comprising a strong amphipathic alpha helix containing protein transduction domain. Thrombolytic protein molecule(s) so engineered with the protein transduction domain is useful for enhanced uptake of such protein thrombolytic molecule(s) across the cell membranes and tissues including the blood brain barrier and find their use in the treatment of vascular thrombosis including cerebrovascular disorders caused by cerebral thrombosis or cerebral haemorrhage when used a as a therapeutic. The design and processes for cloning, expression, purification and protein transduction of such proteins across cell membranes.
    Type: Application
    Filed: May 11, 2007
    Publication date: January 21, 2010
    Applicant: BHARAT BIOTECH INTERNATIONAL LIMITED
    Inventors: Krishna Murthy Ella, Kandaswamy Sumathy
  • Publication number: 20090226413
    Abstract: It has now been discovered that certain mutant forms of pro-urokinase (“pro-UK”), such as so-called pro-UK mutant “M5” (Lys.sup.300.fwdarw.His)-, perform in the manner of pro-UK in lysing “bad” blood clots (those clots that occlude blood vessels), while sparing hemostatic fibrin in the so-called “good” blood clots (those clots that seal wounds, e.g., after surgery or other tissue injury). Thus, these pro-UK mutants are excellent and safe thrombolytic agents. These advantages allow them to be used in a variety of new methods, devices, and compositions useful for thrombolysis and treating various cardiovascular disorders in clinical situations where administration of other known thrombolytic agents has been too risky or even contraindicated.
    Type: Application
    Filed: July 1, 2008
    Publication date: September 10, 2009
    Inventors: Victor GUREWICH, Jian-Ning LIU, Paolo SARMIENTOS
  • Publication number: 20090123452
    Abstract: Methods for identifying modified proteases with modified substrate specificity or other properties are provided. The methods screen candidate and modified proteases by contacting them with a substrate, such as a serpin, an alpha macroglobulins or a p35 family protein or modified serpins and modified p35 family members or modified alpha macroglobulins, that, upon cleavage of the substrate, traps the protease by forming a stable complex. Also provided are modified proteases.
    Type: Application
    Filed: July 5, 2007
    Publication date: May 14, 2009
    Inventor: Edwin L. Madison
  • Publication number: 20090098049
    Abstract: The disclosure provides fusion polypeptides and constructs useful in targeting molecules including diagnostics and therapeutics to a cell type of interest. The fusion constructs include a protein transduction domain, a ligand domain and a cargo domain. Also provided are methods of treating disease and disorders such as cell proliferative disorders.
    Type: Application
    Filed: September 7, 2005
    Publication date: April 16, 2009
    Applicant: The Regents of the University of California
    Inventors: Steven F Dowdy, Eric L. Snyder
  • Publication number: 20080318320
    Abstract: The present invention relates to the targeted delivery of a delivery vehicle construct which specifically binds to and stimulates endocytosis into cells expressing the urokinase plasminogen activator receptor (uPAR), and particularly human airway epithelia. The delivery vehicle construct comprises a portion of uPA and a cargo linked thereto and is useful for the targeted delivery of the cargo to a cell. In one aspect of the invention, the uPA portion of the delivery vehicle construct comprises the wild-type uPA, a fragment of uPA which has the PAI-1 binding region deleted, or a uPA peptide comprising amino acids 13-19 and is useful for the targeted delivery of the cargo to cells, and in particular to airway epithelia. The present invention also provides a method for delivering the delivery vehicle construct to a cell.
    Type: Application
    Filed: August 30, 2006
    Publication date: December 25, 2008
    Inventors: Michael J. Welsh, Paola T. Drapkin
  • Publication number: 20080286803
    Abstract: This invention relates to the field of determining, assaying or quantifying activity of components of the complement system. More particularly, the invention relates to methods for detecting the presence or level of activity in a sample of mannan-binding-lectin associated serine proteases (MASPs) or complexes of such proteases with lectins and to detection of the particular lectins themselves. Provided is a method for determining the activity of a MASP in a sample, comprising incubating the sample with a pro-urokinase comprising at its activation site the consensus sequence Arg/Leu/Gly-Yyy-Arg/Lys-Ile/Leu/Val-Zzz-Gly-Gly cleavable by a MASP, wherein Yyy can be any amino acid and Zzz is preferably an aliphatic amino acid, and determining proteolytic activation of said pro-urokinase.
    Type: Application
    Filed: December 19, 2005
    Publication date: November 20, 2008
    Inventors: Johan Hendrikus Verheijen, Jan Roeland Occo Hanemaaijer, Natascha Alexandra Van Lent, Johannes Hendrikus Nicolaas Lindeman, Mohamed Rahoef Daha, Johanna Roos
  • Publication number: 20080274958
    Abstract: The present invention provides sequon polypeptides with an amino acid sequence including one or more exogenous O-linked glycosylation sequence of the invention. In addition, the present invention provides methods of making polypeptide conjugates as well as methods of using such conjugates and their pharmaceutical compositions. The invention further provides libraries of sequon polypeptides, wherein each member of such library includes at least one exogenous O-linked glycosylation sequence of the invention. Also provided are methods of making and using such libraries.
    Type: Application
    Filed: July 23, 2007
    Publication date: November 6, 2008
    Applicant: Neose Technologies, Inc.
    Inventor: Shawn DeFrees
  • Publication number: 20080255040
    Abstract: The present invention provides sequon polypeptides with an amino acid sequence including one or more exogenous O-linked glycosylation sequence of the invention. In addition, the present invention provides methods of making polypeptide conjugates as well as methods of using such conjugates and their pharmaceutical compositions. The invention further provides libraries of sequon polypeptides, wherein each member of such library includes at least one exogenous O-linked glycosylation sequence of the invention. Also provided are methods of making and using such libraries.
    Type: Application
    Filed: July 23, 2007
    Publication date: October 16, 2008
    Applicant: Neose Technologies, Inc.
    Inventor: Shawn DeFrees
  • Publication number: 20080248959
    Abstract: The present invention provides sequon polypeptides with an amino acid sequence including one or more exogenous O-linked glycosylation sequence of the invention. In addition, the present invention provides methods of making polypeptide conjugates as well as methods of using such conjugates and their pharmaceutical compositions. The invention further provides libraries of sequon polypeptides, wherein each member of such library includes at least one exogenous O-linked glycosylation sequence of the invention. Also provided are methods of making and using such libraries.
    Type: Application
    Filed: July 23, 2007
    Publication date: October 9, 2008
    Applicant: Neose Technologies, Inc.
    Inventor: Shawn DeFrees
  • Publication number: 20080242607
    Abstract: The present invention provides sequon polypeptides with an amino acid sequence including one or more exogenous O-linked glycosylation sequence of the invention. In addition, the present invention provides methods of making polypeptide conjugates as well as methods of using such conjugates and their pharmaceutical compositions. The invention further provides libraries of sequon polypeptides, wherein each member of such library includes at least one exogenous O-linked glycosylation sequence of the invention. Also provided are methods of making and using such libraries.
    Type: Application
    Filed: July 23, 2007
    Publication date: October 2, 2008
    Applicant: Neose Technologies, Inc.
    Inventor: Shawn DeFrees
  • Patent number: 7074401
    Abstract: It has now been discovered that certain mutant forms of pro-urokinase (“pro-UK”), such as so-called pro-UK mutant “M5” (Lys300?His), perform in the manner of pro-UK in lysing “bad” blood clots (those clots that occlude blood vessels), while sparing hemostatic fibrin in the so-called “good” blood clots (those clots that seal wounds, e.g., after surgery or other tissue injury). Thus, these pro-UK mutants are excellent and safe thrombolytic agents. These advantages allow them to be used in a variety of new methods, devices, and compositions useful for thrombolysis and treating various cardiovascular disorders in clinical situations where administration of other known thrombolytic agents has been too risky or even contraindicated.
    Type: Grant
    Filed: April 16, 2004
    Date of Patent: July 11, 2006
    Assignee: Thrombolytic Science, Inc.
    Inventors: Victor Gurewich, John N. Williams, Jian-Ning Liu, Paolo Sarmientos, Massimiliano Pagani
  • Patent number: 7045280
    Abstract: The present invention provides a method for the measurement of the activity of a plasminogen activator, such as urokinase plasminogen activator (uPA) or tissue plasminogen activator (tPA) in a biological sample using an assay method characterized by the inclusion of an elastase inhibitor in the assay mixture. The invention also provides a diagnostic kit for the measurement of a plasminogen activator using said method and a method of determining the effective therapeutic dose of a plasminogen activator inhibitor using said method. Also provided is a method of preparing a pharmaceutical composition.
    Type: Grant
    Filed: December 5, 2000
    Date of Patent: May 16, 2006
    Assignee: AstraZeneca AB
    Inventors: Paul Elvin, Philip Edwin Pinder
  • Patent number: 7041479
    Abstract: Compositions and methods are provided for the enhanced in vitro synthesis of polypeptides containing disulfide bonds. In order to improve the performance of in vitro protein synthesis reactions, pre-treatment and redox buffering of the reaction mix is performed in order to optimize the redox potential. Exogenous enzymes that enhance protein folding and disulfide bond formation may also be added to the reaction.
    Type: Grant
    Filed: March 31, 2003
    Date of Patent: May 9, 2006
    Assignee: The Board of Trustess of the Leland Stanford Junior University
    Inventors: James Robert Swartz, Dong-Myung Kim
  • Patent number: 7022673
    Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.
    Type: Grant
    Filed: April 11, 2002
    Date of Patent: April 4, 2006
    Assignee: Chiron Corporation
    Inventors: Robert J. Drummond, Steve Rosenberg
  • Patent number: 6964764
    Abstract: Methods of thrombolysis that allow the use of a fibrinolytic composition comprising reversibly inactivated acidified plasmin and the localized delivery of the plasmin to a vascular thrombotic occlusion are disclosed. Further disclosed is a method for administering a therapeutic dose of a fibrinolytic composition substantially free of plasminogen activator to a human or animal having a vascular thrombotic occlusion. The fibrinolytic composition includes a reversibly inactivated acidified plasmin substantially free of plasminogen activator. Intravascular catheter delivery of the fibrinolytic composition directly into or in the immediate vicinity of the thrombus is disclosed to minimize the systemic degradation of fibrin while retaining the maximum plasmin activity against the thrombus.
    Type: Grant
    Filed: May 10, 2002
    Date of Patent: November 15, 2005
    Assignee: Talecris Biotherapeutics, Inc.
    Inventors: Thomas P. Zimmerman, Valery Novokhatny, Kyle A. Landskroner, Gary J. Jesmok, Kathryn K. Taylor
  • Patent number: 6902884
    Abstract: Method of diagnosing and/or prognosticating HIV infection in a subject comprising the steps of: (a) performing in vitro a measurement of the level of a marker in the form of (i) urokinase plasminogen activator receptor (uPAR), (ii) soluble urokinase plasminogen activator receptor (suPAR), (iii) urokinase-type plasminogen activator (uPA), (iv) one or more degradation products of (i), (ii), or (iii), and/or (v) an mRNA for (i), (ii) or (iii), in a biological fluid sample from a subject, and (b) using the measurement value obtained to evaluate the state of the subject.
    Type: Grant
    Filed: November 27, 2000
    Date of Patent: June 7, 2005
    Assignee: Virogates ApS
    Inventor: Jesper Eugen-Olsen
  • Patent number: 6899877
    Abstract: A process for inhibiting vascular proliferation separately introduces components into the eye to generate plasmin in the eye in amounts to induce complete posterior vitreous detachment where the vitreoretinal interface is devoid of cortical vitreous remnants. The process administers a combination of lysine-plasminogen, at least one recombinant plasminogen activator selected from the group consisting of urokinase, streptokinase, tissue plasminogen activator, chondroitinase, pro-urokinase, retavase, metaloproteinase, and thermolysin and a gaseous adjuvant to form a cavity in the vitreous. The composition is introduced into the vitreous in an amount effective to induce crosslinking of the vitreous and to induce substantially complete posterior vitreous detachment from the retina without causing inflammation of the retina.
    Type: Grant
    Filed: August 26, 2002
    Date of Patent: May 31, 2005
    Assignee: Minu, L.L.C.
    Inventor: Gholam A. Peyman
  • Patent number: 6846656
    Abstract: The present invention provides a process for economically producing N-acetylneuraminic acid without using expensive materials such as pyruvic acid and phosphoenolpyruvic acid. The process comprises: allowing (i) a culture of a microorganism having N-acetylneuraminic acid aldolase activity or N-acetylneuraminic acid synthetase activity, or a treated matter of the culture, (ii) a culture of a microorganism capable of producing pyruvic acid or a treated matter of the culture, or a culture of a microorganism capable of producing phosphoenolpyruvic acid or a treated matter of the culture, (iii) N-acetylmannosamine, and (iv) an energy source which is necessary for the formation of pyruvic acid or phosphoenolpyruvic acid to be present in an aqueous medium to form and accumulate N-acetylneuraminic acid in the aqueous medium; and recovering N-acetylneuraminic acid from the aqueous medium.
    Type: Grant
    Filed: August 25, 2000
    Date of Patent: January 25, 2005
    Assignee: Kyowa Hakko Kogyo Co., Ltd.
    Inventors: Satoshi Koizumi, Kazuhiko Tabata, Tetsuo Endo, Akio Ozaki
  • Publication number: 20040265298
    Abstract: Highly efficient methods of producing properly folded recombinant urokinase are provided. Denatured recombinant pro-urokinase is refolded by first solubilizing the protein with a chaotroph at high pH, followed by refolding in the presence of reduced concentrations of chaotroph while the pH is slowly reduced.
    Type: Application
    Filed: April 16, 2004
    Publication date: December 30, 2004
    Inventor: Xinli Lin
  • Patent number: 6680174
    Abstract: The present invention relates to a method of identifying an agent which alters (inhibits, enhances) activity of GDF-9. The method involves combining cells having a receptor for GDF-9 and a gene, wherein expression of the gene is regulated by binding of GDF-9 to the receptor; GDF-9; and an agent to be assessed. The combination produced is maintained under conditions appropriate for binding of GDF-9 to the receptors on the cells. The extent to which binding of GDF-9 to the receptors on the cells occurs is then determined, wherein binding of GDF-9 to the receptor to a lesser or greater extent in the presence of the agent to be assessed than in its absence, is indicative of an agent which alters GDF-9 activity.
    Type: Grant
    Filed: April 1, 1999
    Date of Patent: January 20, 2004
    Assignee: Baylor College of Medicine
    Inventors: Martin M. Matzuk, Julia A. Elvin, Pei Wang