Title:
COMPOSITIONS FOR PROLONGING THE SURVIVAL AFTER ORTHOPIC AND HETEROPIC XENOGENEIC HEART, KIDNEY, LUNG OR LIVER TRANSPLANTATIONS
Document Type and Number:
WIPO Patent Application WO/2019/185936
Kind Code:
A3
Abstract:
The present invention relates to methods for prolonging the survival of a primate that is transplanted a genetically modified heart, kidney, lung or liver from a xenogeneic mammal in a life supporting technique, and to compositions for use in a method of prolonging the survival of a primate that has been transplanted a genetically modified heart, kidney, lung or liver from a xenogeneic mammal in a life supporting technique. The invention is also directed to a living primate, whose heart, kidney, lung or liver is functionally substituted by a transplanted, genetically modified heart, kidney, lung or liver, respectively, from a xenogeneic mammal. Finally, the invention is directed to a genetically modified mammal and a donor organism for xenogeneic organ transplants as well as to methods of producing same.
Inventors:
REICHART BRUNO (DE)
ABICHT JAN-MICHAEL (DE)
MAYR TANJA (DE)
LÄNGIN MATTHIAS (DE)
BRENNER PAOLO (DE)
WOLF ECKHARD (DE)
KLYMIUK NIKOLAI (DE)
ABICHT JAN-MICHAEL (DE)
MAYR TANJA (DE)
LÄNGIN MATTHIAS (DE)
BRENNER PAOLO (DE)
WOLF ECKHARD (DE)
KLYMIUK NIKOLAI (DE)
Application Number:
PCT/EP2019/058115
Publication Date:
December 05, 2019
Filing Date:
March 29, 2019
Export Citation:
Assignee:
REICHART BRUNO (DE)
International Classes:
A61K31/436; A01K67/027; A61K31/138; A61K31/401; A61K45/06; A61P37/06
Domestic Patent References:
| WO2006041763A1 | 2006-04-20 | |||
| WO1999016437A1 | 1999-04-08 |
Other References:
KLINTMALM G.B. & NASHAN B.: "The Role of mTOR Inhibitors in Liver Transplantation:Reviewing the Evidence", J. TRANSPL., vol. 2014, 845438, 2014, pages 1 - 45, XP002794870, DOI: 10.1155/2014/845438
DAVID K. C. COOPER ET AL: "Progress in pig-to-non-human primate transplantation models (1998-2013): a comprehensive review of the literature", XENOTRANSPLANTATION, vol. 21, no. 5, 1 September 2014 (2014-09-01), US, pages 397 - 419, XP055505566, ISSN: 0908-665X, DOI: 10.1111/xen.12127
BURCIN EKSER ET AL: "Therapeutic issues in the treatment of vascularized xenotransplants using gal-knockout donors in nonhuman primates :", CURRENT OPINION IN ORGAN TRANSPLANTATION, vol. 16, no. 2, 1 April 2011 (2011-04-01), US, pages 222 - 230, XP055505539, ISSN: 1087-2418, DOI: 10.1097/MOT.0b013e3283446c3c
MCGREGOR ET AL: "Cardiac xenotransplantation: Recent preclinical progress with 3-month median survival", JOURNAL OF THORACIC AND CARDIOVASCULAR SURG, vol. 130, no. 3, 1 September 2005 (2005-09-01), MOSBY-YEAR BOOK, INC., ST. LOUIS, MO, US, pages 844.e1 - 844.e9, XP005087684, ISSN: 0022-5223, DOI: 10.1016/J.JTCVS.2005.04.017
BRANDL ET AL: "Transgenic Animals in Experimental Xenotransplantation Models: Orthotopic Heart Transplantation in the Pig-to-Baboon Model", TRANSPLANTATION PROCEED., vol. 39, no. 2, 13 March 2007 (2007-03-13), , ELSEVIER INC, ORLANDO, FL; US, pages 577 - 578, XP005931660, ISSN: 0041-1345, DOI: 10.1016/J.TRANSPROCEED.2006.12.021
ANDREAS BAUER ET AL: "hDAF porcine cardiac xenograft maintains cardiac output after orthotopic transplantation into baboon - a perioperative study", XENOTRANSPLANTATION, vol. 12, no. 6, 1 November 2005 (2005-11-01), US, pages 444 - 449, XP055505577, ISSN: 0908-665X, DOI: 10.1111/j.1399-3089.2005.00242.x
LARS H. LUND ET AL: "The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Heart Transplantation Report-2017; Focus Theme: Allograft ischemic time", JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol. 36, no. 10, 1 October 2017 (2017-10-01), US, pages 1037 - 1046, XP055506497, ISSN: 1053-2498, DOI: 10.1016/j.healun.2017.07.019
PAOLO BRENNER ET AL: "40 Days Survival after Orthotopic Cardiac Xenotransplantation of Multi-Transgenic Pig Hearts in a Pig-to-Baboon Model with CD40mAb or CD40L Costimulation Blockade and Xenograft Preservation using "Steens" Cold Blood Cardioplegia Perfusion", TRANSPLANTATION, vol. 101, no. 5S-3, 24 May 2017 (2017-05-24), pages S65, XP055506519
GARCIA B ET AL: "Xenotransplantation of human decay accelerating factor transgenic porcine kidney to non-human primates: 4 years experience at a Canadian center", TRANSPLANTATION PROCEED, vol. 36, no. 6, 1 July 2004 (2004-07-01), ELSEVIER INC, ORLANDO, FL; US, pages 1714 - 1716, XP004550708, ISSN: 0041-1345, DOI: 10.1016/J.TRANSPROCEED.2004.06.018
YAMADA K. ET AL.: "Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha-1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue", NATURE MED., vol. 11, no. 1, 26 December 2004 (2004-12-26), pages 32 - 34, XP002794871
IWASE H. ET AL.: "Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date.", XENOTRANSPLANTATION, vol. 22, 2015, pages 302 - 309, XP002794872
HAYATO IWASE ET AL: "Pig-to-baboon heterotopic heart transplantation - exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade-based regimens", XENOTRANSPLANTATION, vol. 22, no. 3, 3 April 2015 (2015-04-03), US, pages 211 - 220, XP055404091, ISSN: 0908-665X, DOI: 10.1111/xen.12167
SFRISO R. ET AL.: "Activation of complement and coagulation in xenotransplantation: Effect of growth hormone receptor knockout on porcine aortic endothelial cells", IMMUNOBIOLOGY, vol. 221, no. 10, 98, September 2016 (2016-09-01), pages 1174 - 1175, XP002794873
MARTENS G.R.: "Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs.", TRANSPLANTATION, vol. 101, no. 4, April 2017 (2017-04-01), pages E86 - E92, XP055544939, DOI: 10.1097/TP.0000000000001646
FISCHER K. ET AL.: "Efficient production of multi-modified pigs for xenotransplantation by 'combineering', gene stacking and gene editing.", SCI. REPORTS, vol. 6, 29081, June 2016 (2016-06-01), XP002794875
KLYMIUK NIKOLAI ET AL: "Genetic Modification of Pigs as Organ Donors for Xenotransplantation", MOLECULAR REPRODUCTION AND DEVELOPMENT, vol. 77, no. 3, 1 March 2010 (2010-03-01), WILEY-LISS, INC, NEW YORK, NY, US, pages 209 - 221, XP009135636, ISSN: 1040-452X, [retrieved on 20091208], DOI: 10.1002/MRD.21127
WOLF-VAN BUERCK L. ET AL.: "LEA29Y expression in transgenic neonatal porcine islet-like cluster promotes long-lasting xenograft survival in humanized mice without immunosuppressive therapy.", SCI. REPORTS, vol. 7, no. 1, 3572, 15 June 2017 (2017-06-15), XP002794876
LÄNGIN M. ET AL.: "Consistent success in life-supporting porcie cardiac xenotransplantation (includes Methods)", NATURE, vol. 564, 27 December 2018 (2018-12-27), pages 430 - 433+8pp, XP002794877
DAVID K. C. COOPER ET AL: "Progress in pig-to-non-human primate transplantation models (1998-2013): a comprehensive review of the literature", XENOTRANSPLANTATION, vol. 21, no. 5, 1 September 2014 (2014-09-01), US, pages 397 - 419, XP055505566, ISSN: 0908-665X, DOI: 10.1111/xen.12127
BURCIN EKSER ET AL: "Therapeutic issues in the treatment of vascularized xenotransplants using gal-knockout donors in nonhuman primates :", CURRENT OPINION IN ORGAN TRANSPLANTATION, vol. 16, no. 2, 1 April 2011 (2011-04-01), US, pages 222 - 230, XP055505539, ISSN: 1087-2418, DOI: 10.1097/MOT.0b013e3283446c3c
MCGREGOR ET AL: "Cardiac xenotransplantation: Recent preclinical progress with 3-month median survival", JOURNAL OF THORACIC AND CARDIOVASCULAR SURG, vol. 130, no. 3, 1 September 2005 (2005-09-01), MOSBY-YEAR BOOK, INC., ST. LOUIS, MO, US, pages 844.e1 - 844.e9, XP005087684, ISSN: 0022-5223, DOI: 10.1016/J.JTCVS.2005.04.017
BRANDL ET AL: "Transgenic Animals in Experimental Xenotransplantation Models: Orthotopic Heart Transplantation in the Pig-to-Baboon Model", TRANSPLANTATION PROCEED., vol. 39, no. 2, 13 March 2007 (2007-03-13), , ELSEVIER INC, ORLANDO, FL; US, pages 577 - 578, XP005931660, ISSN: 0041-1345, DOI: 10.1016/J.TRANSPROCEED.2006.12.021
ANDREAS BAUER ET AL: "hDAF porcine cardiac xenograft maintains cardiac output after orthotopic transplantation into baboon - a perioperative study", XENOTRANSPLANTATION, vol. 12, no. 6, 1 November 2005 (2005-11-01), US, pages 444 - 449, XP055505577, ISSN: 0908-665X, DOI: 10.1111/j.1399-3089.2005.00242.x
LARS H. LUND ET AL: "The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Heart Transplantation Report-2017; Focus Theme: Allograft ischemic time", JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol. 36, no. 10, 1 October 2017 (2017-10-01), US, pages 1037 - 1046, XP055506497, ISSN: 1053-2498, DOI: 10.1016/j.healun.2017.07.019
PAOLO BRENNER ET AL: "40 Days Survival after Orthotopic Cardiac Xenotransplantation of Multi-Transgenic Pig Hearts in a Pig-to-Baboon Model with CD40mAb or CD40L Costimulation Blockade and Xenograft Preservation using "Steens" Cold Blood Cardioplegia Perfusion", TRANSPLANTATION, vol. 101, no. 5S-3, 24 May 2017 (2017-05-24), pages S65, XP055506519
GARCIA B ET AL: "Xenotransplantation of human decay accelerating factor transgenic porcine kidney to non-human primates: 4 years experience at a Canadian center", TRANSPLANTATION PROCEED, vol. 36, no. 6, 1 July 2004 (2004-07-01), ELSEVIER INC, ORLANDO, FL; US, pages 1714 - 1716, XP004550708, ISSN: 0041-1345, DOI: 10.1016/J.TRANSPROCEED.2004.06.018
YAMADA K. ET AL.: "Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha-1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue", NATURE MED., vol. 11, no. 1, 26 December 2004 (2004-12-26), pages 32 - 34, XP002794871
IWASE H. ET AL.: "Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date.", XENOTRANSPLANTATION, vol. 22, 2015, pages 302 - 309, XP002794872
HAYATO IWASE ET AL: "Pig-to-baboon heterotopic heart transplantation - exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade-based regimens", XENOTRANSPLANTATION, vol. 22, no. 3, 3 April 2015 (2015-04-03), US, pages 211 - 220, XP055404091, ISSN: 0908-665X, DOI: 10.1111/xen.12167
SFRISO R. ET AL.: "Activation of complement and coagulation in xenotransplantation: Effect of growth hormone receptor knockout on porcine aortic endothelial cells", IMMUNOBIOLOGY, vol. 221, no. 10, 98, September 2016 (2016-09-01), pages 1174 - 1175, XP002794873
MARTENS G.R.: "Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs.", TRANSPLANTATION, vol. 101, no. 4, April 2017 (2017-04-01), pages E86 - E92, XP055544939, DOI: 10.1097/TP.0000000000001646
FISCHER K. ET AL.: "Efficient production of multi-modified pigs for xenotransplantation by 'combineering', gene stacking and gene editing.", SCI. REPORTS, vol. 6, 29081, June 2016 (2016-06-01), XP002794875
KLYMIUK NIKOLAI ET AL: "Genetic Modification of Pigs as Organ Donors for Xenotransplantation", MOLECULAR REPRODUCTION AND DEVELOPMENT, vol. 77, no. 3, 1 March 2010 (2010-03-01), WILEY-LISS, INC, NEW YORK, NY, US, pages 209 - 221, XP009135636, ISSN: 1040-452X, [retrieved on 20091208], DOI: 10.1002/MRD.21127
WOLF-VAN BUERCK L. ET AL.: "LEA29Y expression in transgenic neonatal porcine islet-like cluster promotes long-lasting xenograft survival in humanized mice without immunosuppressive therapy.", SCI. REPORTS, vol. 7, no. 1, 3572, 15 June 2017 (2017-06-15), XP002794876
LÄNGIN M. ET AL.: "Consistent success in life-supporting porcie cardiac xenotransplantation (includes Methods)", NATURE, vol. 564, 27 December 2018 (2018-12-27), pages 430 - 433+8pp, XP002794877
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HOFFMANN EITLE PATENT- UND RECHTSANWÄLTE PARTMBB (DE)
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