| 序号 | 专利名 | 申请号 | 申请日 | 公开（公告）号 | 公开（公告）日 | 发明人 |
|---|---|---|---|---|---|---|
| 101 | Enzyme and Preparation Method | US10598280 | 2005-03-07 | US20080020416A1 | 2008-01-24 | Mark McAlister; Antonio Pineda-Lucena |
| A method for preparing a soluble protein comprising urokinase-type plasminogen activator (uPA) or an active fragment thereof, or a variant of either of these which has uPA activity, which method comprises contacting said protein with a buffer at a pH of from 8.5-10.5, said buffer comprising a reducing agent and an oxidising agent which forms a redox pair, wherein the reducing agent is present in excess compared to the oxidising agent, and wherein the reducing agent is present in a concentration of at least 5 mM. Material obtainable in this way forms a further aspect of the invention. It has been refolded in a “native-like” form and is useful in studies such as N.M.R. analysis to detect ligands. | ||||||
| 102 | Targeting of Herpes Simplex Virus to Specific Receptors | US11677026 | 2007-02-20 | US20070243170A1 | 2007-10-18 | Bernard Roizman; Guoying Zhou |
| The invention relates to engineered herpes simplex virus (HSV) particles that are targeted to one or more specific binding pair members, such as receptors. Also, recombinant vectors for producing such HSV particles are provided. By reducing the affinity of HSV for its natural receptor(s) and increasing the affinity for a selected receptor, the HSV particles of the invention are useful for targeting cells that express the selected receptor, which itself may be a product of genetic engineering. The ability to selectively target cells renders the HSV particles particularly useful in selectively diagnosing, treating, and imaging cells bearing the selected binding pair member, such as a receptor. The invention also provides for polynucleotide-based therapy to cells bearing the selected binding pair member such as a receptor. | ||||||
| 103 | Remodeling and glycoconjugation of peptides | US11404266 | 2006-04-12 | US07276475B2 | 2007-10-02 | Shawn DeFrees; David A. Zopf; Caryn Bowe |
| The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group a peptide. | ||||||
| 104 | Malarial animal model having a chimeric human liver | US11207176 | 2005-08-17 | US07273963B2 | 2007-09-25 | Norman M. Kneteman; John B. Sacci, Jr.; D. Lorne Tyrrell; John F. Elliott; Abdu F. Azad |
| The present invention features a non-human animal model of malaria, e.g., Plasmodium, particularly Plasmodium falciparum. The model is based on a non-human, immunocompromised transgenic animal having a human-mouse chimeric liver, where the transgene provides for expression of a urokinase-type plasminogen activator in the liver. The invention also features methods for identifying candidate therapeutic agents, e.g., agents having anti-pathogenic activity against malaria. | ||||||
| 105 | Methods, devices, and compositions for lysis of occlusive blood clots while sparing wound sealing clots | US11447455 | 2006-06-06 | US20070148160A1 | 2007-06-28 | Victor Gurewich; Jian-Ning Liu; Paolo Sarmientos |
| 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. | ||||||
| 106 | Method for increasing the serum half-life of a biologically active molecule | US11701298 | 2007-01-31 | US20070135349A1 | 2007-06-14 | Robert Drummond; Steve Rosenberg |
| 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. | ||||||
| 107 | Carrier chimeric proteins, targeted carrier chimeric proteins and preparation thereof | US11483433 | 2006-07-07 | US20070123457A1 | 2007-05-31 | Mustapha Abdelouahed |
| A chimeric carrier protein having a multimerization domain and at least one drug attached thereto via a spacer is disclosed. The protein may be targeted by associating at least one amino acid sequence having an amino acid domain targeted to a specific site of action. In a further embodiment of the invention a nucleic acid molecule is provided which encodes the protein. Vectors containing the nucleic acid molecule and the host cells containing the vectors may also be provided. A method for producing the carrier chimeric protein on the targeted carrier chimeric protein is also disclosed. | ||||||
| 108 | Methods for production of recombinant urokinase | US11444594 | 2006-05-31 | US20070009506A1 | 2007-01-11 | Xinli Lin |
| 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. | ||||||
| 109 | Remodeling and glycoconjugation of peptides | US11404266 | 2006-04-12 | US20060287223A1 | 2006-12-21 | Shawn DeFrees; David Zopf; Caryn Bowe |
| The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group a peptide. | ||||||
| 110 | Method for increasing the serum half-life of a biologically active molecule | US10123092 | 2002-04-11 | US07022673B2 | 2006-04-04 | Robert J. Drummond; Steve Rosenberg |
| 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. | ||||||
| 111 | Propagation of human hepatocytes in non-human animals | US09930781 | 2001-08-15 | US06995299B2 | 2006-02-07 | George Y. Wu; Catherine H. Wu |
| The present invention relates to the preparation of non-human animals having chimeric livers, whereby some or substantially all of the hepatocytes present are human hepatocytes. It is based, at least in part, on the discovery that rats, tolerized in utero against human hepatocytes, were found to serve as long-term hosts for human hepatocytes introduced post-natally, and the introduced hepatocytes maintained their differentiated phenotype, as evidenced by continued production of human albumin. The present invention further relates to the use of such animals as models of various liver diseases, including viral invention. Such embodiments are based on the discovery that transplanted human hepatocytes in chimeric livers were found to be susceptible to Hepatitis B virus and Hepatitis C virus infection. | ||||||
| 112 | Cyclic peptidomimetic urokinase receptor antagonists | US10031401 | 2000-07-19 | US06906032B1 | 2005-06-14 | Olaf Wilhelm; Horst Kessler; Markus Bürgle; Nils Potthoff; Niko Schmiedeberg |
| The present invention relates to cyclic peptides as inhibitors of urokinase binding to the urokinase receptor. Said cyclic peptides are suitable as pharmaceutical active substances for disorders mediated by urokinase and its receptor. | ||||||
| 113 | Inhibitors for urokinase receptor | US09402464 | 1999-04-14 | US06872702B1 | 2005-03-29 | Horst Kessler; Heinrich Graeff; Manfred Schmitt; Viktor Magdolen; Olaf G. Wilhelm; Christoph Riemer; Markus Bürgle |
| The present invention concerns peptides as inhibitors of the binding of urokinase to the urokinase receptor. These peptides, which are preferably cyclic, are suitable as pharmaceutical agents for diseases that are mediated by urokinase and its receptor. | ||||||
| 114 | Methods of making pro-urokinase mutants | US10826598 | 2004-04-16 | US20050019863A1 | 2005-01-27 | Paolo Sarmientos; Massimiliano Pagani |
| Methods are provided for producing non-glycosylated, single-chain and two-chain pro-urokinase (pro-UK) mutants. The methods include cultivating a specific E. coli type B strain that has been transformed with specific plasmids carrying a cDNA sequence that encodes pro-UK mutants and carries specific promoter sequences. Products produced by the methods have medical use for thrombolysis performed while sparing hemostatic clots, e.g., for particular applications such as after a stroke or heart attack. | ||||||
| 115 | Propagation of human hepatocytes in non-human animals | US10819564 | 2004-04-07 | US20050005312A1 | 2005-01-06 | George Wu; Catherine Wu |
| The present invention relates to the preparation of non-human animals having chimeric livers, whereby some or substantially all of the hepatocytes present are human hepatocytes. It is based, at least in part, on the discovery that rats, tolerized in utero against human hepatocytes, were found to serve as long-term hosts for human hepatocytes introduced post-natally, and the introduced hepatocytes maintained their differentiated phenotype, as evidenced by continued production of human albumin. The present invention further relates to the use of such animals as models of various liver diseases, including viral invention. Such embodiments are based on the discovery that transplanted human hepatocytes in chimeric livers were found to be susceptible to Hepatitis B virus and Hepatitis C virus infection. | ||||||
| 116 | Cyclic peptide ligands that target urokinase plasminogen activator receptor | US10744927 | 2003-12-22 | US20040204348A1 | 2004-10-14 | Terence R. Jones; David N. Haney; Janos Varga; Andrew P. Mazar |
| uPAR-targeting cyclic peptide compounds have 11 amino acids that correspond to human uPA(20-30) nullSEQ ID NO:2null, or are substitution variants at selected positions. The N and C terminal residues of these peptides are joined by a linking group L, so that the linear dimension between the null-carbons of the first and the eleventh amino acids is between about 4 and 12 Angstrom units. These cyclic peptides may be further conjugated to diagnostic labels or therapeutic moieties such as radionuclides. Such compounds are useful for targeting uPAR expressed in pathological tissues and for inhibiting the binding of uPA to the uPAR. The pharmaceutical and therapeutic compositions inhibit cell migration, cell invasion, cell proliferation or angiogenesis, or induce apoptosis, and are thus useful for treating diseases or condition associated with undesired cell migration, invasion, proliferation, or angiogenesis, most notably cancer. The cyclic peptides are also used to detect and isolate cells expressing uPAR. | ||||||
| 117 | Remodeling and glycoconjugation of peptides | US10287994 | 2002-11-05 | US20040137557A1 | 2004-07-15 | Shawn DeFrees; David Zopf; Robert Bayer; Caryn Bowe; David Hakes; Xi Chen |
| The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group a peptide. | ||||||
| 118 | Kringle polypeptides and methods for using them to inhibit angiogenesis | US10425000 | 2003-04-29 | US20040052777A1 | 2004-03-18 | Mark Nesbit; Beatrice Cameron; Francis Blanche |
| The present invention relates to kringle polypeptides and polynucleotides encoding kringle polypeptides and their use as therapeutic agents and in methods of identifying agonist compounds. In effect, the kringle polypeptides according to the present invention are particularly useful for inhibiting in vitro and in vivo proliferation, migration and/or invasion of endothelial cells, recruitment of smooth muscle cells, and/or the formation of vasculature in a tissue. The present invention also relates to the use of kringle polypeptides for treating and/or preventing angiogenesis in tumors and inhibiting the growth of tumors. The present invention further relates to a method of modulating angiogenesis in cells affected by an angiogenic-dependent process and inhibiting unwanted or unregulated angiogenesis in an angiogenesis-associated disease. The present invention also concerns a method of production and purification of kringle polypeptides in a soluble and active form. | ||||||
| 119 | Anti-invasive and anti-angiogenic compositions | US09437136 | 1999-11-10 | US06696416B1 | 2004-02-24 | Andrew P. Mazar; Terence R. Jones |
| A peptide compound having the sequence Lys-Pro-Ser-Ser-Pro-Pro-Glu-Glu [SEQ ID NO:2] or a substitution variant, addition variant or other chemical derivative thereof inhibits cell invasion, endothelial tube formation or angiogenesis in vitro. A number of substitution variants and addition variants of this peptide, preferably capped at the N- and C-termini, as well as peptidomimetic derivatives, are useful for treating diseases and conditions mediated by undesired and uncontrolled cell invasion and/or angiogenesis. Pharmaceutical compositions comprising the above peptides and derivatives are administered to subjects in need of such treatment in a dosage sufficient to inhibit invasion and/or angiogenesis . The disclosed compositions and methods are particularly useful for suppressing the growth and metastasis of tumors. | ||||||
| 120 | Urokinase-type plasminogen activator receptor | US09755109 | 2001-01-08 | US20030027981A1 | 2003-02-06 | Keld Dano; Francesco Blasi; Ann Louring Roldan; Maria Vittoria Cubellis; Maria Teresa Masucci; Ettore Appella; Wolf-Dieter Schleuning; Niels Behrendt; Ebbe Ronne; Peter Kristensen; Jari Pollanen; Eeva-Marjatta Salonen; Ross W. Stephens; Hannele Tapiovaara; Antti Vaheri; Lisbeth Birk Moller; Vincent Ellis; Leif Roge Lund; Michael Ploug; Charles Pyke; Laszlo Patthy |
| A polypeptide presenting an epitope cross-reactive with an epitope of urokinase-type plasminogen activator receptor, and/or having uPA binding activity, is described. | ||||||
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