JP2005504507A5 - - Google Patents
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- JP2005504507A5 JP2005504507A5 JP2002570676A JP2002570676A JP2005504507A5 JP 2005504507 A5 JP2005504507 A5 JP 2005504507A5 JP 2002570676 A JP2002570676 A JP 2002570676A JP 2002570676 A JP2002570676 A JP 2002570676A JP 2005504507 A5 JP2005504507 A5 JP 2005504507A5
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| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5625126A (en) * | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| ES2246502T3 (es) | 1990-08-29 | 2006-02-16 | Genpharm International, Inc. | Animales no humanos transgenicos capaces de producir anticuerpos heterologos. |
| US5789650A (en) * | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| ES2301158T3 (es) * | 1992-07-24 | 2008-06-16 | Amgen Fremont Inc. | Produccion de anticuerpos xenogenicos. |
| CA2157659C (en) | 1993-03-16 | 2003-10-21 | Mauro S. Sandrin | Use of porcine gal .alpha. (1,3) galactosyl transferase in xenograft therapies |
| WO1995016670A1 (en) | 1993-12-16 | 1995-06-22 | The Procter & Gamble Company | Process for making sulfonated fatty acid alkyl ester surfactant |
| US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
| US5639940A (en) * | 1994-03-03 | 1997-06-17 | Pharmaceutical Proteins Ltd. | Production of fibrinogen in transgenic animals |
| CA2219361C (en) | 1995-04-27 | 2012-02-28 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5683993A (en) | 1995-06-22 | 1997-11-04 | Ciba Vision Corporation | Compositions and methods for stabilizing polymers |
| JP3030092B2 (ja) | 1995-08-29 | 2000-04-10 | 麒麟麦酒株式会社 | キメラ動物およびその作製法 |
| EP0773288A3 (en) | 1995-08-29 | 1997-07-09 | Kirin Brewery | Chimera animal and its method of manufacture |
| EP1972194A1 (en) | 1996-12-03 | 2008-09-24 | Amgen Fremont Inc. | Transgenic mammals having human ig loci including plural vh and vk regions and antibodies produced therefrom |
| TWI255853B (en) | 1998-08-21 | 2006-06-01 | Kirin Brewery | Method for modifying chromosomes |
| WO2001035735A1 (en) * | 1999-11-19 | 2001-05-25 | Hematech, Llc | Production of ungulates, preferably bovines that produce human immunoglobulins |
| US6721750B1 (en) | 2001-07-03 | 2004-04-13 | Bellsouth Intellectual Property Corporation | System and method for broadband capacity tracking |
-
2001
- 2001-11-16 NZ NZ525664A patent/NZ525664A/en not_active IP Right Cessation
- 2001-11-16 MX MXPA03004313A patent/MXPA03004313A/es not_active Application Discontinuation
- 2001-11-16 AU AU2001297523A patent/AU2001297523B2/en not_active Expired
- 2001-11-16 AT AT01273248T patent/ATE432343T1/de not_active IP Right Cessation
- 2001-11-16 AT AT08016978T patent/ATE503012T1/de not_active IP Right Cessation
- 2001-11-16 WO PCT/US2001/043128 patent/WO2002070648A2/en not_active Ceased
- 2001-11-16 KR KR1020077030804A patent/KR100882030B1/ko not_active Expired - Fee Related
- 2001-11-16 JP JP2002570676A patent/JP3797974B2/ja not_active Expired - Fee Related
- 2001-11-16 CN CN018220762A patent/CN1486365B/zh not_active Expired - Lifetime
- 2001-11-16 EP EP01273248A patent/EP1343880B1/en not_active Expired - Lifetime
- 2001-11-16 EP EP08016978A patent/EP2042594B1/en not_active Expired - Lifetime
- 2001-11-16 CA CA2428053A patent/CA2428053C/en not_active Expired - Lifetime
- 2001-11-16 DE DE60144305T patent/DE60144305D1/de not_active Expired - Lifetime
- 2001-11-16 DE DE60138832T patent/DE60138832D1/de not_active Expired - Lifetime
- 2001-11-16 KR KR1020037006659A patent/KR100882029B1/ko not_active Expired - Fee Related
-
2005
- 2005-05-09 JP JP2005136675A patent/JP2005224250A/ja active Pending
-
2007
- 2007-04-17 AU AU2007201700A patent/AU2007201700A1/en not_active Abandoned
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