NZ525664A - Expression of xenogenous (human) immunoglobulins in cloned, transgenic ungulates - Google Patents
Expression of xenogenous (human) immunoglobulins in cloned, transgenic ungulatesInfo
- Publication number
- NZ525664A NZ525664A NZ525664A NZ52566401A NZ525664A NZ 525664 A NZ525664 A NZ 525664A NZ 525664 A NZ525664 A NZ 525664A NZ 52566401 A NZ52566401 A NZ 52566401A NZ 525664 A NZ525664 A NZ 525664A
- Authority
- NZ
- New Zealand
- Prior art keywords
- ungulate
- nucleic acid
- cell
- human
- gene
- Prior art date
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- Molecular Biology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71418500A | 2000-11-17 | 2000-11-17 | |
| US25645800P | 2000-12-20 | 2000-12-20 | |
| US31162501P | 2001-08-09 | 2001-08-09 | |
| PCT/US2001/043128 WO2002070648A2 (en) | 2000-11-17 | 2001-11-16 | Expression of xenogenous (human) immunoglobulins in cloned, transgenic ungulates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ525664A true NZ525664A (en) | 2008-08-29 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ525664A NZ525664A (en) | 2000-11-17 | 2001-11-16 | Expression of xenogenous (human) immunoglobulins in cloned, transgenic ungulates |
Country Status (11)
| Country | Link |
|---|---|
| EP (2) | EP2042594B1 (OSRAM) |
| JP (2) | JP3797974B2 (OSRAM) |
| KR (2) | KR100882030B1 (OSRAM) |
| CN (1) | CN1486365B (OSRAM) |
| AT (2) | ATE432343T1 (OSRAM) |
| AU (2) | AU2001297523B2 (OSRAM) |
| CA (1) | CA2428053C (OSRAM) |
| DE (2) | DE60144305D1 (OSRAM) |
| MX (1) | MXPA03004313A (OSRAM) |
| NZ (1) | NZ525664A (OSRAM) |
| WO (1) | WO2002070648A2 (OSRAM) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7414170B2 (en) | 1999-11-19 | 2008-08-19 | Kirin Beer Kabushiki Kaisha | Transgenic bovines capable of human antibody production |
| US7074983B2 (en) | 1999-11-19 | 2006-07-11 | Kirin Beer Kabushiki Kaisha | Transgenic bovine comprising human immunoglobulin loci and producing human immunoglobulin |
| GB0110029D0 (en) | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
| NZ536341A (en) * | 2002-05-17 | 2008-05-30 | Kirin Holdings Kk | Transgenic ungulates capable of human antibody production |
| CA2501068C (en) * | 2002-10-04 | 2014-12-16 | Kirin Beer Kabushiki Kaisha | Human artificial chromosome (hac) vector |
| JP2006505291A (ja) | 2002-11-08 | 2006-02-16 | ヘマテック，エルエルシー | プリオンタンパク質活性が低減されたトランスジェニック有蹄動物及びその用途 |
| CA2535859A1 (en) * | 2003-08-14 | 2005-03-03 | Dyax Corp. | Endotheliase-2 ligands |
| BRPI0415147A (pt) * | 2003-09-30 | 2006-11-28 | Sterrenbeld Biotechnologie North America Inc | método para a produção de uma proteìna, método para a purificação de um hormÈnio de crescimento recombinante do leite de um mamìfero transgênico não humano que produz um hormÈnio de crescimento recombinante e método para a purificação de um hormÈnio de crescimento recombinante do leite de um mamìfero não transgênico que produz um hormÈnio de crescimento recombinante |
| WO2005104835A2 (en) * | 2004-04-22 | 2005-11-10 | Kirin Beer Kabushiki Kaisha | Transgenic animals and uses thereof |
| US20080026457A1 (en) | 2004-10-22 | 2008-01-31 | Kevin Wells | Ungulates with genetically modified immune systems |
| CA2958259C (en) * | 2004-10-22 | 2020-06-30 | Revivicor, Inc. | Ungulates with genetically modified immune systems |
| WO2006117910A1 (ja) | 2005-04-28 | 2006-11-09 | Mochida Pharmaceutical Co., Ltd. | 抗血小板膜糖蛋白質ⅵモノクローナル抗体 |
| DK2348827T3 (en) | 2008-10-27 | 2015-07-20 | Revivicor Inc | IMMUNICIPLY COMPROMATED PETS |
| RU2011129459A (ru) * | 2008-12-18 | 2013-01-27 | Эрасмус Юниверсити Медикал Сентр Роттердам | Трансгенные животные (не человек), экспрессирующие гуманизированные антитела, и их применение |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| PT2564695E (pt) | 2009-07-08 | 2015-06-03 | Kymab Ltd | Modelos animais e moléculas terapêuticas |
| CN102803488A (zh) | 2009-11-17 | 2012-11-28 | 协和发酵麒麟株式会社 | 人类人工染色体载体 |
| WO2013041844A2 (en) | 2011-09-19 | 2013-03-28 | Kymab Limited | Antibodies, variable domains & chains tailored for human use |
| WO2013042426A1 (ja) | 2011-09-21 | 2013-03-28 | 富士レビオ株式会社 | 親和性複合体に対する抗体 |
| WO2013045916A1 (en) | 2011-09-26 | 2013-04-04 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| SG10201805622QA (en) * | 2011-12-22 | 2018-08-30 | Hoffmann La Roche | Expression Vector Organization, Novel Production Cell Generation Methods And Their Use For The Recombinant Production Of Polypeptides |
| US10251377B2 (en) | 2012-03-28 | 2019-04-09 | Kymab Limited | Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies |
| GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
| CN104755493B (zh) | 2012-08-03 | 2020-12-25 | Sab有限责任公司 | 用于在转基因动物中生产人类抗体的复杂的染色体工程 |
| US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
| US9783618B2 (en) | 2013-05-01 | 2017-10-10 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
| US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
| NL2013554B1 (en) | 2013-10-01 | 2016-01-08 | Kymab Ltd | Animal models and therapeutic molecules. |
| AU2015360502A1 (en) | 2014-12-10 | 2017-06-29 | Regents Of The University Of Minnesota | Genetically modified cells, tissues, and organs for treating disease |
| WO2017218714A1 (en) * | 2016-06-14 | 2017-12-21 | Regents Of The University Of Minnesota | Genetically modified cells, tissues, and organs for treating disease |
| US12063913B2 (en) | 2016-10-31 | 2024-08-20 | National University Corporation Tottori University | Human antibody-producing non-human animal and method for preparing human antibodies using same |
| EP4103603A4 (en) * | 2020-02-12 | 2024-03-27 | Sab, Llc | ANTI-THYMOCYTE GLOBULIN |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5789650A (en) * | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| CA2089661C (en) | 1990-08-29 | 2007-04-03 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5770429A (en) * | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | 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 |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| SG48760A1 (en) * | 1992-07-24 | 2003-03-18 | Abgenix Inc | Generation of xenogenetic antibodies |
| CA2157659C (en) | 1993-03-16 | 2003-10-21 | Mauro S. Sandrin | Use of porcine gal .alpha. (1,3) galactosyl transferase in xenograft therapies |
| CN1054840C (zh) | 1993-12-16 | 2000-07-26 | 普罗格特-甘布尔公司 | 制备磺化脂肪酸烷酯表面活性剂的方法 |
| 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 |
| ATE390933T1 (de) | 1995-04-27 | 2008-04-15 | Amgen Fremont Inc | Aus immunisierten xenomäusen stammende menschliche antikörper gegen il-8 |
| 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 |
| AU718138B2 (en) | 1995-08-29 | 2000-04-06 | Kyowa Hakko Kirin Co., Ltd. | Chimeric animal and method for constructing the same |
| EP2314625B1 (en) | 1996-12-03 | 2014-05-07 | Amgen Fremont Inc. | Transgenic mammals having human Ig loci including plural VH and Vkappa regions and antibodies produced therefrom |
| TWI255853B (en) | 1998-08-21 | 2006-06-01 | Kirin Brewery | Method for modifying chromosomes |
| AU1777301A (en) * | 1999-11-19 | 2001-05-30 | 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 WO PCT/US2001/043128 patent/WO2002070648A2/en not_active Ceased
- 2001-11-16 DE DE60144305T patent/DE60144305D1/de not_active Expired - Lifetime
- 2001-11-16 NZ NZ525664A patent/NZ525664A/en not_active IP Right Cessation
- 2001-11-16 EP EP08016978A patent/EP2042594B1/en not_active Expired - Lifetime
- 2001-11-16 KR KR1020077030804A patent/KR100882030B1/ko not_active Expired - Fee Related
- 2001-11-16 MX MXPA03004313A patent/MXPA03004313A/es not_active Application Discontinuation
- 2001-11-16 KR KR1020037006659A patent/KR100882029B1/ko 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 AT AT01273248T patent/ATE432343T1/de not_active IP Right Cessation
- 2001-11-16 CA CA2428053A patent/CA2428053C/en not_active Expired - Lifetime
- 2001-11-16 AU AU2001297523A patent/AU2001297523B2/en not_active Expired
- 2001-11-16 DE DE60138832T patent/DE60138832D1/de not_active Expired - Lifetime
- 2001-11-16 JP JP2002570676A patent/JP3797974B2/ja not_active Expired - Fee Related
- 2001-11-16 AT AT08016978T patent/ATE503012T1/de not_active IP Right Cessation
-
2005
- 2005-05-09 JP JP2005136675A patent/JP2005224250A/ja active Pending
-
2007
- 2007-04-17 AU AU2007201700A patent/AU2007201700A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| KR20080005616A (ko) | 2008-01-14 |
| KR100882030B1 (ko) | 2009-02-09 |
| CN1486365A (zh) | 2004-03-31 |
| AU2007201700A1 (en) | 2007-05-10 |
| JP2005224250A (ja) | 2005-08-25 |
| EP1343880A2 (en) | 2003-09-17 |
| EP2042594B1 (en) | 2011-03-23 |
| ATE503012T1 (de) | 2011-04-15 |
| CN1486365B (zh) | 2010-05-12 |
| KR100882029B1 (ko) | 2009-02-09 |
| EP1343880B1 (en) | 2009-05-27 |
| CA2428053C (en) | 2012-08-21 |
| WO2002070648A2 (en) | 2002-09-12 |
| DE60144305D1 (de) | 2011-05-05 |
| MXPA03004313A (es) | 2007-02-27 |
| ATE432343T1 (de) | 2009-06-15 |
| CA2428053A1 (en) | 2002-09-12 |
| AU2001297523B2 (en) | 2007-01-18 |
| KR20030059260A (ko) | 2003-07-07 |
| DE60138832D1 (de) | 2009-07-09 |
| JP3797974B2 (ja) | 2006-07-19 |
| WO2002070648A3 (en) | 2003-02-13 |
| JP2005504507A (ja) | 2005-02-17 |
| EP2042594A1 (en) | 2009-04-01 |
| EP1343880A4 (en) | 2005-03-16 |
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