JP2005523681A - Ｕｌ１６結合タンパク質４ - Google Patents
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| US20030022239A1 (en) | 1997-06-18 | 2003-01-30 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| WO1999031241A1 (en) | 1997-12-17 | 1999-06-24 | Immunex Corporation | Cell surface glycoproteins associated with human b cell lymphomas - ulbp, dna and polypeptides |
| AU758004B2 (en) | 1997-12-17 | 2003-03-13 | Genset S.A. | Extended cDNAs for secreted proteins |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| CA2378403A1 (en) | 1999-07-26 | 2001-02-01 | Genentech, Inc. | Novel polynucleotides and method for the use thereof |
| CA2391455A1 (en) * | 1999-12-01 | 2001-06-07 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| WO2001049728A2 (en) * | 2000-01-06 | 2001-07-12 | Protegene Inc. | HUMAN PROTEINS HAVING HYDROPHOBIC DOMAINS AND DNAs ENCODING THESE PROTEINS |
| US20040219521A1 (en) * | 2000-01-21 | 2004-11-04 | Tang Y. Tom | Novel nucleic acids and polypeptides |
| EP1266014A2 (en) | 2000-03-24 | 2002-12-18 | Peter Kufer | Multifunctional polypeptides comprising a binding site to an epitope of the nkg2d receptor complex |
| US20050074754A1 (en) * | 2000-04-27 | 2005-04-07 | Shoichi Okubo | Novel protein and use thereof |
| EP1278778A2 (en) | 2000-05-03 | 2003-01-29 | Amgen Inc., | Modified peptides, comprising an fc domain, as therapeutic agents |
| WO2002068615A2 (en) | 2001-02-28 | 2002-09-06 | Fred Hutchinson Cancer Research Center, Inc. | Activation of lymphocyte populations expressing nkg2d using anti-nkg2d antibodies and ligand derivatives |
| US6821522B2 (en) * | 2001-05-31 | 2004-11-23 | The Regents Of The University Of California | Tumor Therapy |
| CA2456369A1 (en) | 2001-08-08 | 2003-02-20 | Incyte Genomics, Inc. | Proteins associated with cell growth, differentiation, and death |
| WO2003054152A2 (en) | 2001-12-10 | 2003-07-03 | Nuvelo, Inc. | Novel nucleic acids and polypeptides |
| WO2003074556A1 (fr) | 2002-03-04 | 2003-09-12 | Shanghai Genomics, Inc. | Marqueur tumoral et ses applications |
| AU2003270063A1 (en) | 2002-09-04 | 2004-03-29 | The Trustees Of The University Of Pennsylvania | Immune cell receptor ligand and immune cell receptor |
-
2002
- 2002-10-04 JP JP2003532654A patent/JP2005523681A/ja active Pending
- 2002-10-04 AT AT02778459T patent/ATE434624T1/de not_active IP Right Cessation
- 2002-10-04 PL PL02373594A patent/PL373594A1/xx unknown
- 2002-10-04 US US10/265,811 patent/US7563450B2/en not_active Expired - Fee Related
- 2002-10-04 DE DE60232742T patent/DE60232742D1/de not_active Expired - Lifetime
- 2002-10-04 CA CA002462790A patent/CA2462790A1/en not_active Abandoned
- 2002-10-04 AU AU2002340118A patent/AU2002340118B2/en not_active Ceased
- 2002-10-04 MX MXPA04003057A patent/MXPA04003057A/es unknown
- 2002-10-04 EP EP02778459A patent/EP1451333B1/en not_active Expired - Lifetime
- 2002-10-04 WO PCT/US2002/031994 patent/WO2003029436A2/en not_active Ceased
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2009
- 2009-06-05 US US12/479,543 patent/US8129167B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US8129167B2 (en) | 2012-03-06 |
| PL373594A1 (en) | 2005-09-05 |
| US20090274699A1 (en) | 2009-11-05 |
| ATE434624T1 (de) | 2009-07-15 |
| WO2003029436A3 (en) | 2003-11-13 |
| EP1451333A2 (en) | 2004-09-01 |
| MXPA04003057A (es) | 2005-06-20 |
| US7563450B2 (en) | 2009-07-21 |
| CA2462790A1 (en) | 2003-04-10 |
| AU2002340118B2 (en) | 2007-09-13 |
| EP1451333B1 (en) | 2009-06-24 |
| DE60232742D1 (de) | 2009-08-06 |
| US20030195337A1 (en) | 2003-10-16 |
| EP1451333A4 (en) | 2005-03-30 |
| WO2003029436A2 (en) | 2003-04-10 |
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