| 序号 | 专利名 | 申请号 | 申请日 | 公开（公告）号 | 公开（公告）日 | 发明人 |
|---|---|---|---|---|---|---|
| 121 | Method for increasing the serum half-life of a biologically active molecule | US09263117 | 1999-03-05 | US06423685B1 | 2002-07-23 | 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. | ||||||
| 122 | METHOD FOR INCREASING THE SERUM HALF-LIFE OF A BIOLOGICALLY ACTIVE MOLECULE | US09263117 | 1999-03-05 | US20020086819A1 | 2002-07-04 | 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 nulluPAnull or nullhUPAnull) 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. | ||||||
| 123 | Pharmaceutical preparation containing protein C and a thrombolytically active substance | US07899866 | 1992-06-17 | US06403556B1 | 2002-06-11 | Johann Eibl; Anton Philapitsch; Hans Peter Schwarz |
| A pharmaceutical preparation contains protein C and a thrombolytically active substance that does not activate protein C. This preparation prevents reocclusion usually occurring in the course of thrombolysis therapy. | ||||||
| 124 | Pathogen-targeted biocatalysts | US09410882 | 1999-10-04 | US06287561B1 | 2001-09-11 | Roberto Crea |
| This invention pertains to biocatalysts that are specifically targeted to bind pathogens, such as viruses, and to degrade components of pathogens in order to abrogate their pathogenicity, and to methods of preventing or treating infection by pathogenic organisms. The biocatalysts comprise a binding agent which specifically binds a surface component of a pathogen, for instance the gp120 viral coat protein of the Human Immunodeficiency Virus, and a catalytic moiety which degrades a component of the pathogen so that its pathogenicity is abrogated. The binding agent and the catalytic moiety are linked by chemical linkers or genetic engineering techniques. | ||||||
| 125 | Antibodies and their use | US580166 | 1995-12-28 | US6113897A | 2000-09-05 | Keld Dan.o slashed.; Ebbe R.o slashed.nne; Niels Behrendt; Vincent Ellis; Gunilla H.o slashed.yer-Hansen; Charles Pyke; Nils Bruenner |
| A monoclonal or polyclonal antibody directed against urokinase plasminogen activator receptor (u-PAR), or a subsequence, analogue or glycosylation variant thereof. Antibodies are disclosed which react with free u-PAR or with complexes between u-PA and u-PAR and which are capable of 1) catching u-PAR in ELISA, or 2) detecting u-PAR, e.g. in blotting, or 3) in radioimmunoprecipitation assay precipitate purified u-PAR in intact or fragment form, or 4) is useful for immunohistochemical detection of u-PAR, e.g. in immunostaining of cancer cells, such as in tissue sections at the invasive front, or 5) inhibits the binding of pro-u-PA and active u-PA and thereby inhibits cell surface plasminogen activation. Methods are disclosed 1) for detecting or quantifying u-PAR, 2) for targeting a diagnostic to a cell containing a u-PAR on the surface, 3) for preventing or counteracting proteolytic activity in a mammal. Methods for for selecting a substance suitable for inhibiting u-PA/u-PAR interaction, for preventing or counteracting localized proteolytical activity in a mammal, for inhibiting the invasion and/or metastasis comprise the use of the antibodies and of nude mice inoculated with human cancer cells which are known to invade and/or metastasize in mice and having a distinct color, f.x. obtained by means of an enzyme and a chromogenic substrate for the enzyme, the color being different from the cells of the mouse. | ||||||
| 126 | Peptide analog inhibitors of urokinase receptor activity | US800213 | 1997-02-12 | US6030940A | 2000-02-29 | Steven Rosenberg; Kerry L. Spear; Robert Valerio; Andrew Bray |
| Effective urokinase-type plasminogen activator receptor antagonists have sequences selected from the group LNFGQYLWYT, LCFGCYLWYT, LNFGCYLWCT, LNFGQYLnAYT, LNFdSQYLWYT, LCFGCYLWY, LNFdSQYLnAYT, LNFGdCYLWCT, LCFdSCYLWYT, LCFdSCYLnAYT, LNFdSCYLWCT, or active analogs or active portions thereof. | ||||||
| 127 | Pathogen-targeted biocatalysts | US558269 | 1995-11-13 | US5961973A | 1999-10-05 | Roberto Crea |
| This invention pertains to biocatalysts that are specifically targeted to bind pathogens, such as viruses, and to degrade components of pathogens in order to abrogate their pathogenicity, and to methods of preventing or treating infection by pathogenic organisms. The biocatalysts comprise a binding agent which specifically binds a surface component of a pathogen, for instance the gp120 viral coat protein of the Human Immunodeficiency Virus, and a catalytic moiety which degrades a component of the pathogen so that its pathogenicity is abrogated. The binding agent and the catalytic moiety are linked by chemical linkers or genetic engineering techniques. | ||||||
| 128 | Pharmaceutical preparation containing protein C and a thrombolytically active substance | US456684 | 1995-06-01 | US5830467A | 1998-11-03 | Johann Eibl; Anton Philapitsch; Hans Peter Schwarz |
| A pharmaceutical preparation contains protein C and a thrombolytically active substance that does not activate protein C. This preparation prevents reocclusion usually occurring in the course of thrombolysis therapy. | ||||||
| 129 | Oligonucleotides encloding peptide inhibitors of urokinase receptor activity | US438759 | 1995-05-10 | US5679782A | 1997-10-21 | Steven Rosenberg; Michael V. Doyle |
| Oligonucleotides encoding effective urokinase-type plasminogen activator receptor antagonists have amino acid sequences selected from the group AEPMPHSLNFSQYLWYT, AEWHPGLSFGSYLWSKT, AEHTYSSLWDTYSPLAF, AESSLWTRYAWPSMPSY, AELDLWMRHYPLSFSNR, AEWSFYNLHLPEPQTIF, AETLFMDLWHDKHILLT, AEPLDLWSLYSLPPLAM, AESLPTLTSILWGKESV, AESQTGTLNTLFWNTLR, AESSLWRIFSPSALMMS, AEPALLNWSFFFNPGLH, AEAWFLSNTMKALSARL, AEPTLWQLYQFPLRLSG, AEISFSELMWLRSTPAF, AEWITSSPPLTQYLWGF, AEMHRSLWEWYVPNQSA, AEIKTDEKMGLWDLYSM, AEILNFPLWHEPLWSTE, AELSEADLWITWFGMGS, AESVQYSKLWKPNTTLA, AEPLSLYQKKTLRHFAN, AELPRTNPVTAVKNPSF, AEQLNRSIPDLQFSMFN, and AESHIKSLLDSSTWFLP, or active analogs or active portions thereof. | ||||||
| 130 | Peptide inhibitors of urokinase receptor activity | US370567 | 1995-01-09 | US5656726A | 1997-08-12 | Steven Rosenberg; Michael V. Doyle |
| Effective urokinase-type plasminogen activator receptor antagonists have sequences selected from the group AEPMPHSLNFSQYLWYT, AEWHPGLSFGSYLWSKT, AEHTYSSLWDTYSPLAF, AESSLWTRYAWPSMPSY, AELDLWMRHYPLSFSNR, AEWSFYNLIHILPEPQTIF, AETLFMDLWHDKHILLT, AEPLDLWSLYSLPLAM, AESLPTLTSILWGKESV, AESQTGTLNTLFWNTLR, AESSLWRIFSPSALMMS, AEPALLNWSFFFNPGLH, AEAWFLSNTMKALSARL, AEPTLWQLYQFPLRLSG, AEISFSELMWLRSTPAF, AEWITSSPPLTQYLWGF, AEMHRSLWEWYVPNQSA, AEIKTDFXGWLGLWDLYSM, AEILNFPLWHEPLWSTE, AELSEADLWITWFGMGS, AESVQYSKLWKPNTTLA, AEPLSLYQKKTLRHFAN, AELPRTNPVTAVKNPSF, AEQLNRSIPDLQFSMFN, and AESHIKSLLDSSTWFLP, or active analogs or active portions thereof. | ||||||
| 131 | Plasmids, their construction and their use in the manufacture of a plasminogen activator | US551907 | 1990-07-12 | US5637503A | 1997-06-10 | Regina E. Brigelius-Flohe' ; Leopold Flohe' ; Wolfgang Hillen; Gerd J. Steffens; Wolfgang Strassburger; Martin R. F. Wilhelm |
| Plasmids containing synthetic DNA sequences are described which are suitable for the expression of the intermediate protein of the recombinant scu-PA (i.e., the unglycosylated protein moiety of the single chain prourokinase) in Enterobacteriaceae, especially in E. coli, with expression rates far higher than those obtainable according to prior methods. The plasmids comprise operons that include a regulatable, optionally synthetic, promotor, a Shine-Dalgarno sequence, a start codon, a synthetic structural gene with selected codon usage, and downstream of the structural gene, 1 to 2 transcription terminators. The preparation of the plasmids and of synthetic DNA-sequences starting from commercially available plasmids and intermediates is described. The intermediate protein, expressed in high yields by using the plasmids for transforming suitable hosts, may be refolded to produce the therapeutically useful plasminogen activator recombinant scu-PA. This protein also may serve as a starting material for obtaining the recombinant two chain unglycosylated urokinase protein (rtcu-PA) on a large scale by splitting the single chain product. | ||||||
| 132 | Urokinase-type plasminogen activator receptor antibodies | US85122 | 1993-06-17 | US5519120A | 1996-05-21 | Keld Dano; Ebbe Ronne; Niels Behrendt; Vincent Ellis; Gunilla Hoyer-Hansen; Charles Pyke; Nils Bruenner |
| A monoclonal or polyclonal antibody directed against urokinase plasminogen activator receptor (u-PAR), or a subsequence, analogue or glycosylation variant thereof. Antibodies are disclosed which react with free u-PAR or with complexes between u-PA and u-PAR and which are capable of 1) catching u-PAR in ELISA, or 2) detecting u-PAR, e.g. in blotting, or 3) in radioimmunoprecipitation assay precipitate purified u-PAR in intact or fragment form, or 4) is useful for immunohistochemical detection of u-PAR, e.g. in immunostaining of cancer cells, such as in tissue sections at the invasive front, or 5) inhibits the binding of pro-u-PA and active u-PA and thereby inhibits cell surface plasminogen activation. Methods are disclosed 1) for detecting or quantifying u-PAR, 2) for targeting a diagnostic to a cell containing a u-PAR on the surface, 3) for preventing or counteracting proteolytic activity in a mammal. Methods for for selecting a substance suitable for inhibiting u-PA/u-PAR interaction, for preventing or counteracting localized proteolytical activity in a mammal, for inhibiting the invasion and/or metastasis comprise the use of the antibodies and of nude mice inoculated with human cancer cells which are known to invade and/or metastasize in mice and having a distinct color, f.x. obtained by means of an enzyme and a chromogenic substrate for the enzyme, the color being different from the cells of the mouse. | ||||||
| 133 | Plasminogen activator | US899634 | 1992-06-16 | US5342775A | 1994-08-30 | Shigeyoshi Yasumura; Tatsunari Nishi; Seiga Ito |
| A novel plasminogen activator which is identical in peptide sequence to naturally occurring human prourokinase except that the 155th amino acid counting from the N-terminal amino acid (serine)] is other than the 155th amino acid (proline) of naturally occurring human prourokinase, optionally with the addition of methionine at the N terminus. | ||||||
| 134 | Effective thrombosis mediated by human prourokinase-like polypeptides with increased binding affinity for thrombosis | US651363 | 1991-02-12 | US5316934A | 1994-05-31 | Yoh-ichi Kobayashi; Ken Watabe; Yukuo Mukohara; Masayuki Satoh; Hiroaki Nakamura |
| Human prourokinase-like polypeptides of which oligopeptides having a structure to form a covalent bond with blood clot (thrombus) through enzymatic action of human blood coagulation factor XIII are attached to the NH.sub.2 -terminal sides of human prourokinase derivatives. | ||||||
| 135 | Process for the purification and pasteurization of urokinase | US590557 | 1990-09-28 | US5156967A | 1992-10-20 | Eric Paques |
| A process for the purification and pasteurization of urokinase using an ion exchanger is described, the product obtained having a favorable ratio of high molecular weight to low molecular weight urokinase. The product can be used for therapeutic purposes. | ||||||
| 136 | Pharmaceutically active conjugates having improved body tissue binding specificity | US359662 | 1989-07-21 | US5151412A | 1992-09-29 | Robert A. Brown |
| Pharmaceutically active conjugates comprising a pharmaceutically active substance for treating a disorder of the body that involves a specified body tissue conjugated directly or indirectly with at least one fragment of an adhesive glycoprotein such as fibronectin, the said glycoprotein fragment(s) having improved binding specificity compared with the parent protein for the said body tissue. | ||||||
| 137 | DNA sequences encoding human t-PA substituted at position 275 or at positions 275 and 277 and pharmaceutical compositions | US741120 | 1991-08-05 | US5147643A | 1992-09-15 | Herbert L. Heyneker |
| Biologically active mutant tissue plasminogen activators are disclosed wherein site directed mutagenesis, for example, of a two-chain activation site renders the mutants resistant to conversion to the two-chain form. | ||||||
| 138 | Stabilized plasminogen activator precursor and method of producing the same | US512511 | 1990-04-20 | US5075230A | 1991-12-24 | Kazuo Morimoto; Motoshi Sagane; Kazuhiro Ohara; Shusaku Narita |
| A plasminogen activator precursor obtainable from a serum-free culture fluid of human kidney cells is stabilized by adding to its solution poly-C1-C5-alkylene glycols, polyethylene-polyoxypropylene copolymers, mandelic acid salts, triethanolamine, acid addition salts of acetylglycillysine methyl ester, guanidine salts, thiocyanic acid salts, alkali metal iodides or serine. | ||||||
| 139 | Fibrinophilic urokinase complex | US403895 | 1989-09-05 | US5004609A | 1991-04-02 | Shigeru Hayashi; Kaneo Yamada |
| This invention discloses a fibrinophilic urokinase complex which is a complex of urokinase with a urokinase inhibitor or tissue activator inhibitor and has a molecular weight of 97,500.+-.3,000 and a method for the production of this fibrinophilic urokinase complex from urine. The urokinase complex can be used, as a thombolytic agent exhibiting an outstanding ability to dissolve thrombus. | ||||||
| 140 | Fibrinolytic activity enhancer | US252468 | 1988-10-03 | US4996050A | 1991-02-26 | Minoru Tsukada; Kenji Tanaka; Yoshiro Iga |
| A fibrinolytic activity enhancer for signal-chain pro-urokinase comprising plasminogen as an active ingredient is disclosed. The fibrinolytic activity enhancer of the present invention enhances the fibrinolytic activity of single-chain pro-urokinase without causing systemic fibrinolysis. Thus, it is highly useful in the treatment of thrombosis and obstructive diseases. | ||||||
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