ZA200307893B - Treatment of prophylaxis of insulin-producing cell graft rejection. - Google Patents
Treatment of prophylaxis of insulin-producing cell graft rejection. Download PDFInfo
- Publication number
- ZA200307893B ZA200307893B ZA200307893A ZA200307893A ZA200307893B ZA 200307893 B ZA200307893 B ZA 200307893B ZA 200307893 A ZA200307893 A ZA 200307893A ZA 200307893 A ZA200307893 A ZA 200307893A ZA 200307893 B ZA200307893 B ZA 200307893B
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- South Africa
- Prior art keywords
- combination according
- insulin
- antibody
- receptor
- optionally substituted
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- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- A61K39/39541—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against normal tissues, cells
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- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
Landscapes
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Applications Claiming Priority (1)
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| US29706901P | 2001-06-08 | 2001-06-08 |
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| ZA200307893B true ZA200307893B (en) | 2004-09-06 |
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| ZA200307893A ZA200307893B (en) | 2001-06-08 | 2003-10-09 | Treatment of prophylaxis of insulin-producing cell graft rejection. |
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| EP (1) | EP1429845B1 (pt) |
| JP (1) | JP4476623B2 (pt) |
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| AU (1) | AU2002320828B2 (pt) |
| BR (1) | BR0209319A (pt) |
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| PL (1) | PL364359A1 (pt) |
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| RU (1) | RU2003136730A (pt) |
| WO (1) | WO2002100148A2 (pt) |
| ZA (1) | ZA200307893B (pt) |
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|---|---|---|---|---|
| CA2435739A1 (en) * | 2001-02-22 | 2002-09-06 | Novartis Ag | Use of accelerated lymphocyte homing agents for the manufacture of a medicament for the treatment of delayed graft function |
| WO2005110481A2 (en) * | 2004-05-14 | 2005-11-24 | Alexion Pharmaceuticals, Inc. | Prolongation of survival of an allograft by inhibiting complement activity |
| WO2006009092A1 (ja) * | 2004-07-16 | 2006-01-26 | Kyorin Pharmaceutical Co., Ltd. | 効果的な医薬の使用法及び副作用発現の防御に関する方法 |
| EP1819326B1 (en) * | 2004-11-29 | 2014-07-02 | Novartis AG | Dosage regimen of an s1p receptor agonist |
| CN101111259A (zh) * | 2005-02-08 | 2008-01-23 | 诺瓦提斯公司 | 组合s1p受体激动剂/调节剂和免疫抑制药的抗淋巴细胞抗体诱导 |
| US8778327B2 (en) * | 2005-05-11 | 2014-07-15 | Loma Linda University | Substances, compositions and methods for preventing and treating immune-mediated inflammatory disorders |
| US20090191218A1 (en) | 2005-05-11 | 2009-07-30 | Fengchun Li | DNA Vaccines And Methods For The Prevention Of Transplantation Rejection |
| CA2633374C (en) | 2005-12-15 | 2013-10-01 | Mitsubishi Tanabe Pharma Corporation | Amine compound and use thereof for medical purposes |
| RU2445975C2 (ru) * | 2006-03-02 | 2012-03-27 | Алексион Фармасьютикалз, Инк. | Продление срока выживаемости аллотрансплантата путем ингибирования активности комплемента |
| EP3351252B1 (en) * | 2006-09-28 | 2020-04-22 | Loma Linda University | Apoptotic cell-mediated transfection of mammalian cells with interfering rna |
| US8476305B2 (en) | 2008-02-07 | 2013-07-02 | Kyorin Pharmaceutical Co., Ltd. | Therapeutic agent or prophylactic agent for inflammatory bowel disease comprising amino alcohol derivative as active ingredient |
| CA2716058C (en) * | 2008-03-12 | 2016-07-05 | Loma Linda University | Dna vaccines and methods for the prevention of transplantation rejection |
| NZ588505A (en) | 2008-03-17 | 2012-09-28 | Actelion Pharmaceuticals Ltd | Dosing regimen for a selective S1P1 receptor agonist (R)-5-[3-chloro-4-(2,3-dihydroxy-propoxy)-benz[Z]ylidene]-2-([Z]-propylimino)-3-o-tolyl-thiazolidin-4-one |
| ES2643161T3 (es) * | 2008-11-11 | 2017-11-21 | Novartis Ag | Formas cristalinas de HCL de fingolimod |
| EP2358660A2 (en) * | 2008-11-11 | 2011-08-24 | Novartis AG | Salts of fingolimod |
| EP3973855A1 (en) * | 2009-06-30 | 2022-03-30 | Lifescan, Inc. | Analyte testing methods and device for calculating basal insulin therapy |
| WO2011002791A2 (en) * | 2009-06-30 | 2011-01-06 | Lifescan Scotland Limited | Systems for diabetes management and methods |
| RU2559931C2 (ru) * | 2009-09-29 | 2015-08-20 | Лайфскэн Скотлэнд Лимитед | Способ тестирования аналита и устройство для контроля для пациентов, страдающих сахарным диабетом |
| BR112012021572A2 (pt) * | 2010-02-25 | 2016-10-25 | Lifescan Scotland Ltd | método e sistema de teste de análito com notificação de tendências de glicose sanguínea altas e baixas. |
| US11680273B2 (en) | 2011-09-23 | 2023-06-20 | Loma Linda University | Treatment of autoimmune diseases |
| ES2806605T3 (es) | 2011-09-23 | 2021-02-18 | Univ Loma Linda | Cepas bacterianas que expresan genes de metilasa y sus usos |
| CN114306643A (zh) * | 2021-11-30 | 2022-04-12 | 中国科学院昆明动物研究所 | 一种恒河猴免疫抑制模型的构建方法及在car-t细胞植活上的应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2126658T3 (es) * | 1992-10-21 | 1999-04-01 | Yoshitomi Pharmaceutical | Compuesto de 2-amino-1,3-propanodiol e inmunosupresor. |
| US5679546A (en) * | 1993-09-24 | 1997-10-21 | Cytomed, Inc. | Chimeric proteins which block complement activation |
| ES2204944T3 (es) * | 1994-03-03 | 2004-05-01 | Alexion Pharmaceuticals, Inc. | Genes y proteinas de fusion inhibidores del complemento terminal. |
| GB9624038D0 (en) * | 1996-11-19 | 1997-01-08 | Sandoz Ltd | Organic compounds |
| JPH1180026A (ja) * | 1997-09-02 | 1999-03-23 | Yoshitomi Pharmaceut Ind Ltd | 新規免疫抑制剤、その使用方法およびその同定方法 |
| CA2435739A1 (en) * | 2001-02-22 | 2002-09-06 | Novartis Ag | Use of accelerated lymphocyte homing agents for the manufacture of a medicament for the treatment of delayed graft function |
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2002
- 2002-06-07 AT AT02754637T patent/ATE424893T1/de active
- 2002-06-07 DE DE60231522T patent/DE60231522D1/de not_active Expired - Lifetime
- 2002-06-07 CA CA002445605A patent/CA2445605A1/en not_active Abandoned
- 2002-06-07 PL PL02364359A patent/PL364359A1/xx not_active Application Discontinuation
- 2002-06-07 ES ES02754637T patent/ES2322442T3/es not_active Expired - Lifetime
- 2002-06-07 NZ NZ529044A patent/NZ529044A/en unknown
- 2002-06-07 US US10/164,755 patent/US20030003099A1/en not_active Abandoned
- 2002-06-07 RU RU2003136730/15A patent/RU2003136730A/ru not_active Application Discontinuation
- 2002-06-07 WO PCT/EP2002/006278 patent/WO2002100148A2/en active IP Right Grant
- 2002-06-07 JP JP2003502981A patent/JP4476623B2/ja not_active Expired - Fee Related
- 2002-06-07 EP EP02754637A patent/EP1429845B1/en not_active Expired - Lifetime
- 2002-06-07 PT PT02754637T patent/PT1429845E/pt unknown
- 2002-06-07 IL IL15838402A patent/IL158384A0/xx unknown
- 2002-06-07 AU AU2002320828A patent/AU2002320828B2/en not_active Ceased
- 2002-06-07 BR BR0209319-7A patent/BR0209319A/pt not_active IP Right Cessation
- 2002-06-07 CN CNA028098498A patent/CN1524002A/zh active Pending
-
2003
- 2003-10-09 ZA ZA200307893A patent/ZA200307893B/en unknown
- 2003-12-05 NO NO20035434A patent/NO20035434D0/no not_active Application Discontinuation
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2006
- 2006-03-09 US US11/372,383 patent/US20060153842A1/en not_active Abandoned
-
2008
- 2008-04-22 US US12/107,726 patent/US20080199465A1/en not_active Abandoned
-
2011
- 2011-06-06 US US13/154,106 patent/US20110236382A1/en not_active Abandoned
-
2013
- 2013-12-05 US US14/098,179 patent/US20140093502A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20110236382A1 (en) | 2011-09-29 |
| CA2445605A1 (en) | 2002-12-19 |
| PT1429845E (pt) | 2009-06-15 |
| WO2002100148A3 (en) | 2004-04-22 |
| US20060153842A1 (en) | 2006-07-13 |
| CN1524002A (zh) | 2004-08-25 |
| ATE424893T1 (de) | 2009-03-15 |
| IL158384A0 (en) | 2004-05-12 |
| US20030003099A1 (en) | 2003-01-02 |
| ES2322442T3 (es) | 2009-06-22 |
| PL364359A1 (en) | 2004-12-13 |
| AU2002320828B2 (en) | 2006-02-02 |
| US20080199465A1 (en) | 2008-08-21 |
| US20140093502A1 (en) | 2014-04-03 |
| RU2003136730A (ru) | 2005-05-20 |
| WO2002100148A2 (en) | 2002-12-19 |
| NZ529044A (en) | 2008-03-28 |
| DE60231522D1 (de) | 2009-04-23 |
| BR0209319A (pt) | 2004-07-20 |
| EP1429845B1 (en) | 2009-03-11 |
| JP2004534788A (ja) | 2004-11-18 |
| JP4476623B2 (ja) | 2010-06-09 |
| EP1429845A2 (en) | 2004-06-23 |
| NO20035434D0 (no) | 2003-12-05 |
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