IP Library › Granted Patent US 12,714,077
Granted Patent B2
US 12,714,077 · App. 15/758,895 · Granted Aug 25, 2026

Multi-transgenic pig for Xenotransplantation

View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,714,077
App. No.
15/758,895
Filed
Mar 9, 2018
Granted
Aug 25, 2026
Kind
B2
Art Unit
1634
USPC
424/93.21
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 12, 2018
From: AYARES, DAVID L.
To: REVIVICOR, INC.
Reel/Frame 045175/0904 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 12, 2018
From: PHELPS, CAROL
To: REVIVICOR, INC.
Reel/Frame 045175/0063 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 12, 2018
From: AYARES, DAVID L.
To: REVIVICOR, INC.
Reel/Frame 045175/0427 →
Continuity (3)
Provisional Application 62216225 · Sep 9, 2015
Provisional Application 62256068 · Nov 16, 2015
Related Publication 20180249688A1 · Sep 6, 2018
References Cited (191)
US 4736866A · Leder et al. · 1988 [cited by applicant]
US 4873191A · Wagner et al. · 1989 [cited by applicant]
US 4888274A · Radding et al. · 1989 [cited by applicant]
US 4944384A · Herron · 1990 [cited by applicant]
US 5057420A · Massey · 1991 [cited by applicant]
US 5334575A · Noonan et al. · 1994 [cited by applicant]
US 5453457A · Meltzer et al. · 1995 [cited by applicant]
US 5496720A · Susko-Parrish et al. · 1996 [cited by applicant]
US 5523226A · Wheeler · 1996 [cited by applicant]
US 5730403A · Johnson · 1998 [cited by applicant]
US 5747340A · Harats et al. · 1998 [cited by applicant]
US 5821117A · Sandrin et al. · 1998 [cited by applicant]
US 5859307A · Mombaerts et al. · 1999 [cited by applicant]
US 5945577A · Stice et al. · 1999 [cited by applicant]
US 5977318A · Linsley et al. · 1999 [cited by applicant]
US 6066725A · Deboer et al. · 2000 [cited by applicant]
US 6147276A · Campbell et al. · 2000 [cited by applicant]
US 6153428A · Gustafsson et al. · 2000 [cited by applicant]
US 6166288A · Diamond et al. · 2000 [cited by applicant]
US 6215041B1 · Stice et al. · 2001 [cited by applicant]
US 6235969B1 · Stice et al. · 2001 [cited by applicant]
US 6252133B1 · Campbell et al. · 2001 [cited by applicant]
US 6258998B1 · Damiani et al. · 2001 [cited by applicant]
US 6376743B1 · Yanagimachi · 2002 [cited by applicant]
US 6413769B1 · Gustafsson et al. · 2002 [cited by applicant]
US 6423316B1 · Riesbeck et al. · 2002 [cited by applicant]
US 6506559B1 · Fire et al. · 2003 [cited by applicant]
US 6525243B1 · Stockman Campbell et al. · 2003 [cited by applicant]
US 6548741B2 · Desousa et al. · 2003 [cited by applicant]
US 6573099B2 · Graham · 2003 [cited by applicant]
US 6639122B1 · Tu et al. · 2003 [cited by applicant]
US 6872868B1 · Wagner et al. · 2005 [cited by applicant]
US 7304033B2 · Larsen et al. · 2007 [cited by applicant]
US 7368284B2 · Koike · 2008 [cited by applicant]
US 7378569B2 · Tu et al. · 2008 [cited by applicant]
US 7462466B2 · Morgan et al. · 2008 [cited by applicant]
US 7755462B2 · Fullerton et al. · 2010 [cited by applicant]
US 11179496B2 · Ayares · 2021 [cited by applicant]
US 20010044937A1 · Schatten et al. · 2001 [cited by applicant]
US 20020062492A1 · Lubon et al. · 2002 [cited by applicant]
US 20020068713A1 · Rade et al. · 2002 [cited by applicant]
US 20020108132A1 · Rapp · 2002 [cited by applicant]
US 20030014770A1 · Gustafsson et al. · 2003 [cited by applicant]
US 20050155095A1 · Koike · 2005 [cited by applicant]
US 20050223418A1 · Koike · 2005 [cited by applicant]
US 20060068479A1 · Koike · 2006 [cited by applicant]
US 20070113297A1 · Yang et al. · 2007 [cited by applicant]
US 20070286845A1 · Harats et al. · 2007 [cited by applicant]
US 20090186097A1 · Ayares · 2009 [cited by applicant]
US 20110038841A1 · Ayares · 2011 [cited by examiner]
US 20130347134A1 · Diacovo et al. · 2013 [cited by applicant]
US 20140017215A1 · Ayares · 2014 [cited by examiner]
US 20150106962A1 · Sachs et al. · 2015 [cited by applicant]
US 20210392863A1 · Kim et al. · 2021 [cited by applicant]
US 20220072200A1 · Ayares · 2022 [cited by applicant]
CN 1582332 · 2005 [cited by applicant]
CN 108949832A · 2018 [cited by applicant]
WO WO9003432A1 · 1990 [cited by applicant]
WO WO9421799A1 · 1994 [cited by applicant]
WO WO9424274A1 · 1994 [cited by applicant]
WO WO9426884A1 · 1994 [cited by applicant]
WO WO9520661A1 · 1995 [cited by applicant]
WO WO9528412A1 · 1995 [cited by applicant]
WO WO9707668A1 · 1997 [cited by applicant]
WO WO9707669A1 · 1997 [cited by applicant]
WO WO9807841A1 · 1998 [cited by applicant]
WO WO9815626A2 · 1998 [cited by applicant]
WO WO9830683A2 · 1998 [cited by applicant]
WO WO9907829A1 · 1999 [cited by applicant]
WO WO9949029A1 · 1999 [cited by applicant]
WO WO9953042A2 · 1999 [cited by applicant]
WO WO9957266A2 · 1999 [cited by applicant]
WO WO0004217A1 · 2000 [cited by applicant]
WO WO0022098A1 · 2000 [cited by applicant]
WO WO0031126A2 · 2000 [cited by applicant]
WO WO0051424A2 · 2000 [cited by applicant]
WO WO0130966A2 · 2001 [cited by applicant]
WO WO03005810A2 · 2003 [cited by applicant]
WO WO03055302A1 · 2003 [cited by applicant]
WO WO03059923A2 · 2003 [cited by applicant]
WO WO2004016742A2 · 2004 [cited by applicant]
WO WO2004028243A2 · 2004 [cited by applicant]
WO WO2007035213A2 · 2007 [cited by applicant]
WO WO2009069986 · 2009 [cited by applicant]
WO WO2011020120 · 2011 [cited by applicant]
WO WO2012112586 · 2012 [cited by applicant]
WO WO2014066505 · 2014 [cited by applicant]
WO WO2016065046 · 2016 [cited by applicant]
WO WO2019185936A2 · 2019 [cited by applicant]
WO WO2020085788A1 · 2020 [cited by applicant]
Deng et al. (2011) PLoS One, vol. 6(5), e19986, pp. 1-9. [cited by examiner]
Hai et al. (2014) Cell Research, vol. 24, 372-375. [cited by examiner]
Nottle et al. (2007) Xenotransplantation, vol. 14(4), 339-344; doi.org/10.1111/j.1399-3089.2007.00417.x. [cited by examiner]
Deng et al. (2011) PLoS One, vol. 6(5):e19986. doi:10.1371/journal.pone.0011986, pp. 1-9. [cited by examiner]
Harris et al. (2014) Xenotransplantation, vol. 21(6), 496-506, published online Jul. 5, 2014. Doi:10.1111/xen.12116, pp. 1-21. [cited by examiner]
Kriz et al. (2010) Nat. Commun.1:120 doi: 10.1038/ncomms1120, pp. 1-6, and Supplemental Material, pp. 1-21. [cited by examiner]
Tena et al. (2014) Am.J.Tranplant., vol. 14(12):2713-2722.doi:10.1111/ajt.12918. [cited by examiner]
Yu et al. (2003) Mol. Ther., vol. 7(6), 827-838. [cited by examiner]
Quadros et al. (Mar. 10, 2015) FEBS Open Bio, vol. 5, 191-197. [cited by examiner]
Lee et al. (Oct. 2015) Proceedings of the Korean Veterinary Medical Association, p. 544, abstract P300. [cited by examiner]
Estrada et al. (Mar. 2015) Xenotransplantation, vol. 22, 194-202. [cited by examiner]
Aigner et al. (2010) Curr. Opin. Organ Transplant., vol. 15, 201-206. [cited by examiner]
Olsson et al. (2006) Int. J. Biochem. & Cell Biol., vol. 38: 492-497. [cited by examiner]
Ohtsuka et al. (2015) BMC Genomics, vol. 16:274, DOI 10.1186/s12864-015-1432-5, pp. 1-16. [cited by examiner]
Definition of “permit” (2024) Dictionary.com, pp. 1-6. [cited by examiner]
Ayares, David et al.: “Genetic Engineering of Source Pigs for Xenotransplantation: Progress and Pro-spects”, Xenotransplantation, Sep-Oct. 2013, vol. 20, No. 5, 408, Sep. 20, 2013 (Sep. 20, 2013), p. 361. [cited by applicant]
Hayato, Iwase et al.: “Pig Kidney Graft Survival in a Baboon for 136 Days: Longest Life-Supporting Organ Graft Survival to Date”, Xenotransplantation, vol. 22, No. 4, Jun. 29, (Jun. 29, 2015), pp. 302-309. [cited by applicant]
Tang, Hai et al.: “One Step Generation of Knockout Pigs by Zgote Injectcion of CRISPR/Cas System”, Cell Resesarch—Xibao Yanjiu, vol. 24, No. 3, Jan. 31, 2014 (Jan. 31, 2014), pp. 372-375. [cited by applicant]
Hilton, Gock, et al.: “Genetic Modification of Pigs for Solid Organ Xenotransplantation”, Transplanta-tion Reviews, vol. 25, No. 1, Jan. 1, 2011 (Jan. 1, 2011), pp. 9-20. [cited by applicant]
Nella, Fisicaro et al.: “Versatile Co-Expression of Graft-Protective Proteins Using 2A-Linked Cassettes: Transgene Co-Expression Using 2A”, Xenotransplantation, vol. 18, No. 2, Mar. 1, 2011 (Mar. 1, 2011), pp. 121-130. [cited by applicant]
Salvaris, Evelyn et al.: “IXA-0-7.1: Multi-Gene Constructs to Accelerate the Generation of Multi-Transgenic GalT Knockout Pigs”, Xenotransplantation. Sep. 2009, vol. 16, No. 5, Sep. 2009 (Sep. 2009), p. 373. [cited by applicant]
Wei, Deng et al.: “Use of the 2A Peptide for Generation of Multi-Transgenic Pigs through a Single Round of Nuclear Transfer”, Plos One, vol. 6, No. 5, May 13, 2011 (May 13, 2011), p. e19986. [cited by applicant]
David KC Cooper et al.: “Recent Advances in Understanding Xenotransplantation: Implications for the Clinic”, Expert Review of Clinical Immunology, vol. 11, No. 12, Sep. 1, 2015 (Sep. 1, 2015), pp. 1379-1390. [cited by applicant]
Donald G. Harris et al.: “Meta-Analysis of 1-8, the Independent and Cumulative Effects of 11-27 Multi-ple Genetic Modifications on Pig Lung Xenograft Performance During Ex Vivo Perfusion with Human Blood”, Xenotransplan… [cited by applicant]
Hayato, Iwase et al.: “Immunological and Physiological Observations in Baboons with Life-Supporting Genetically Engineered Pig Kidney Grafts”, Xenotransplantation, vol. 24, No. 2, Mar. 17, 2017 (Mar. 17, 2017), p. e1229… [cited by applicant]
U.S. Appl. No. 17/531,416, filed Nov. 19, 2021, Rothblatt et al. [cited by applicant]
Aigner et al., “Transgenic pigs for xenotransplantation: Selection of promoter sequences for reliable transgene expression,” Current Opinion in Organ Transplantation, 2010, 15:201-206. [cited by applicant]
Ayares, “Genetic Modification of Pigs for Regenerative Medicine”, Presentation from UC Davis Transgenic Animal Research Conference VII, Aug. 20, 2009. [cited by applicant]
Ayares, David. “Genetic Modification of Pigs for Xenotransplantation,” Transgenic Research, vol. 19, No. 143 (2010). [cited by applicant]
Bach et al., “Delayed xenograft rejection”, Immunol Today, 1996, vol. 17(8), pp. 379-384. [cited by applicant]
Bronson et al., “Single-copy transgenic mice with chosen-site integration,” Proc. Natl. Acad. Sci. USA, Aug. 1996, 93:9067-9072. [cited by applicant]
Byrne et al., “Increased Immunosuppression, Not Anticoagulation, Extends Cardiac Xenograft Survival,” Transplantation, 2006, 82:1787-1791. [cited by applicant]
Byrne et al., “Transgenic Pigs Expressing Human CD59 and Decay-Accelerating Factor Produce an Intrinsic Barrier to Complement-Mediated Damage1,” Transplantation, 1997, 63(1):149-155. [cited by applicant]
Chen et al., “Complete Inhibition-of Acute Humoral Rejection Using Regulated Expression of Membrane-tethered Anticoagulants on Xenograft Endothelium”, American Journal of Transplantation, 2004, vol. 4, pp. 1958-1963. [cited by applicant]
Chen et al., “Inhibition of intravascular thrombosis in murine endotoxemia by targeted expression of hirudin and tissue factor pathway inhibitor analogs to activated endothelium”, Blood, 2004, vol. 104(5), pp. 1344-1349. [cited by applicant]
Costa et al., “Expression of the human al ,2-fucosyltransferase in transgenic pigs modifies the cell surf ace carbohydrate phenotype and confers resistance to human serum-mediated cytolysis”, Faseb J, 1999, vol. 13, pp.… [cited by applicant]
Cowan et al., “Coagulation and the xenograft endothelium”, Xenotransplantation, 2007, vol. 14(1), pp. 7-12. [cited by applicant]
Cozzi et al., “Preliminary study in a life supporting pig to primate xenotransplantation model using GAL KO pigs transgenic for human CD39, CD55, CD59 and fucosyltransferase,” (Abstract LB IXA O-4), Xenotransplantation,… [cited by applicant]
Dai et al., “Targeted disruption of the a1 ,3-galactosyltransferase gene in cloned pigs”, Nature Biotechnology, 2002, vol. 20, pp. 251-255. [cited by applicant]
Dalmasso et al., “Reaction of Complement With Endothelial Cells in a Model of Xenotransplantation”, Clin. Exp. Immunol., 1991, vol. 86, pp. 31-35. [cited by applicant]
Dalmasso et al., “Inhibition of Complement-Mediated Endothelial Cell Cytotoxicity By Decay-Accelerating Factor”, Transplantation, 1991, vol. 52(3), pp. 530-533. [cited by applicant]
Denning et al., “Deletion of the a(1,3)galactosyl transferase (GGTA 1) gene and the prion protein (PrP) gene in sheep”, Nature Biotechnology, 2001, vol. 19, pp. 559-562. [cited by applicant]
Diamond et al., “Human CD59 expressed in transgenic mouse hearts inhibits the activation of complement”, Transplant Immunology, 1995, vol. 3, pp. 305-312. [cited by applicant]
Dwyer et al., “Thromboregulatory manifestations in human CD39 transgenic mice and the implications for thrombotic disease and transplantation”, The Journal of Clinical Investigation, 2004, vol. 113(10), pp. 1440-1446. [cited by applicant]
Galili et al., “Man, Apes, and Old World Monkeys Differ from Other Mammals in the Expression of a-Galactosyl Epitopes on Nucleated Cells”, The Journal of Biological Chemistry, 1988, vol. 263, pp. 17755-17762. [cited by applicant]
Genbank Accession No. NM_213888.1, 2 pages, downloaded from http://www.ncbi.nlm.nih.gov/nuccore/NM_213888.1 on Feb. 9, 2015. [cited by applicant]
Giraldo et al,. “Size matters: use of YACs, BACs and PACs in transgenic animals,” Transgenic Research, 2001, 10:83-103. [cited by applicant]
Gock et al., “Genetic modification of pigs for solid organ xenotransplantation,” Transplantation Reviews, Jan. 2011, 25:9-20. [cited by applicant]
Godwin et al., “Towards endothelial cell-specific transgene expression in pigs: characterization of the pig ICAM-2 promoter”, Xenotransplantation, 2006, vol. 13(6), pp. 514-521. [cited by applicant]
Harrison et al., “Efficient generation of a.(1,3) galactosyltransferase knockout porcine fetal fibroblasts for nuclear transfer”, Transgenic Research, 2002, vol. 11, pp. 143-150. [cited by applicant]
Houdebine, Louis-Marie, “Relations between animal transgenesis and reproduction,” Reprod. Nutr. Dev., 2005, 45:363-376. [cited by applicant]
Koike et al., “Direct gene replacement of the mouse a(1,3)-galactosyltransferase gene with human a(1,2)-fucosyltransferase gene: Converting a-galactosyl epitopes into H anti.gens”, Xenotransplantation, 1997, vol. 4, pp.… [cited by applicant]
Lai et al., “.Production of a-1,3-Galactosyltransferase Knockout Pigs by Nuclear Transfer Cloning”, Science, 2002, vol. 295, pp. 1089-1092. [cited by applicant]
Larin et al., “A method for linking yeast artificial chromosomes,” Nucleic Acids Research, 1996, 24(21):4192-4196. [cited by applicant]
Lee et al., “Characterization of Transgenic Pigs That Express Human Decay Accelerating Factor and Cell Membrane-tethered Human Tissue Factor Pathway Inhibitor”, Reprod Dom Anim, 2010, pp. 1-8. [cited by applicant]
Lui et al., “Mammary gland-specific secretion of biologically active immunosuppressive agent cytotoxic-T lymphocyte antigen 4 human immunoglobulin fusion protein (CTLA4lg) in milk by transgenesis”, Journal of Immunologi… [cited by applicant]
Martin et al., “Transgenic expression of CTLA4-lg by fetal pig neurons for xenotransplantation”, Transgenic Research, 2005, vol. 14, pp. 373-384. [cited by applicant]
Mirenda et al., “Achieving Permanent Survival of Islet Xenografts by Independent Manipulation of Direct and Indirect T-Cell Responses”, Diabetes, 2005, vol. 54, pp. 1048-1055. [cited by applicant]
Miyagawa et al., “Remodeling of the Major Pig Xenoantigen by N-Acetylglucosaminyltransferase III in Transgenic Pig”, The Journal of Biological Chemistry, 2001, vol. 276(42), pp. 39310-39319. [cited by applicant]
Mohiuddin et al., “One-Year Heterotopic Cardiac Xenograph Survival in a Pig to Baboon Model,” Am. J. Transplant, Feb. 2014, 14(2):488-489. [cited by applicant]
Niemann et al. “Production and characterization of multi-transgenic pigs for xenotransplantation,” Transgenic Research, vol. 19 (2010) (pp. 143-144). [cited by applicant]
Niemann et al., “Production and Characterization of Multi-transgenic Pigs for Xeno Transplantation,” Transgenic Research, 2010, 19:143-144. [cited by applicant]
Phelps et al., “Production of u 1,3-Galactosyltransferase Deficient Pigs”, Science, 2003, vol. 299, pp. 411-414. [cited by applicant]
Piedrahita et al., “Cloning and transgenesis in mammals: Implications for xenotransplantation,” American Journal of Transplantation, 2004, 4(Suppl.6):43-50. [cited by applicant]
Ramsoondar et al., “Production of al,3-Galactosyltransferase-Knockout Cloned Pigs Expressing Human al,2-Fucosylosyltransferase”, Biology of Reproduction, 2003, vol. 69, pp. 437-445. [cited by applicant]
Sachs et al., “Genetic Manipulation in Pigs,” Curr. Opin. Organ Transplant., Apr. 2009, 14(2):148-153. [cited by applicant]
Schlaeger et al., “Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice”, 1997, vol. 94(7), pp. 3058-3063. [cited by applicant]
Shimizu et al., “Thrombotic Microangiopathic Glomerulopathy in Human Decay Accelerating Factor-Transgenic Swine-to-Baboon Kidney Xenografts,” J. Am. Soc. Nephrol., 2005, 16:2732-2745. [cited by applicant]
Sprangers et al., “Xenotransplantation: Where are we in 2008?”, Kidney International, Apr. 16, 2008, 74:14-21. [cited by applicant]
Squinto, “Xenogeneic organ transplantation”, Current Opinion in Biotechnology, Dec. 1996, vol. 7(6), pp. 641-645. [cited by applicant]
Stone et al., “Porcine and Bovine Cartilage Transplants in Cynomolgus Monkey”, Transplantation, 1997, vol. 63(5), pp. 640-645. [cited by applicant]
Strahan et al., “PIG alphal,3GALACTOSYLTRANSFERASE: A Major Target for Genetic Manipulation in Xenotransplantation”, Frontiers in Bioscience, 1996, vol. 1, pp. 34-41. [cited by applicant]
Sutherland et al., “Protective Effect of CTLA4lg Secreted By Transgenic Fetal Pancreas Allografts”, Transplantation, 2000, vol. 69(9), pp. 1806-1812. [cited by applicant]
Tai et al., “Progress in Xenotransplantation Following the Introduction of Gene-knockout Technology,” Transplant International, 2007, 20:107-117. [cited by applicant]
Tanemura et al., “Reduction of the Major Swine Xenoantigen, the a-Galactosyl Epitope by Transfection of the a2,3-Sialyltransferase Gene”, The Journal of Biological Chemistry, 1998, vol. 273(26), pp. 16421-16425. [cited by applicant]
Van de Wouwer et al., “Thrombomodulin-Protein C-EPCR System : Integrated to Regulate Coagulation and Inflammation”, Arterioscler Thromb Vasc Biol, 2004, vol. 24, pp. 1374-1383. [cited by applicant]
van der Windt et al., “Rapid loss of intraportally transplanted islets: an overview of pathophysiology and preventive strategies”, Xenotransplantation, Jul. 2007, vol. 14(4), pp. 288-297. [cited by applicant]
Vaughan et al., “Porcine CTLA4-lg Lacks a MYPPPY Motif, Binds Inefficiently to Human B7 and Specifically Suppresses Human CD4 T Cell Responses Costimulated by Pig But Not Human B7”, The Journal of Immunology, 2000, pp. … [cited by applicant]
Ye et al., “Evidence That Intravenously Administered a-Galactosyl Carbohydrates Reduce Baboon Serum Cytotoxicity to Pig Kidney Cells (PK15) and Transplanted Pig Hearts”, Transplantation, 1994, vol. 58, pp. 330-337. [cited by applicant]
Burdorf et al., “Day Xeno Lung Recipient Survival—Progress towards the Clinic,” Journal of Heart and Lung Transplantation, Apr. 2019, 38(4):S39, 72. [cited by applicant]
Kemter et al., “Xeno-organ donor pigs with multiple genetic modifications—the more the better?”, Current Opinion in Genetics & Development, Jun. 30, 2020, 64:60-65. [cited by applicant]
Niu et al., “Porcine genome engineering for xenotransplantation,” Advanced Drug Delivery Reviews, 2021, 168:229-245. [cited by applicant]
Pierson et al., “Progress Toward Cardiac Xenotransplantation,” Circulation, 142(14):1389-1398. [cited by applicant]
Beaton et al., “GGTA-1 targeting efficiency with a xenograft transgene”, 2012, retrieved from https://mospace.umsystem.edu/xmlui/handle/10355/35385# on Aug. 31, 2022. [cited by applicant]
Kim et al., “Knock-in Somatic Cells of Human Decay Accelerating Factor and a1,2-Fucosyltransferase Gene on the a1,3-Galactosyltransferase Gene Locus of Miniature Pig”, Reprod Dev Biol, 2015, 39(3):59-67. [cited by applicant]
Kim et al., “Porcine Knock-in Fibroblasts Expressing hDAF on a-1,3-Galactosyltransferase (GGTA1) Gene Locus”, Asian-Aust. J. Anim. Sci., 2012, 25:1473-1480. [cited by applicant]
Cooper et al., “Clinical lung xenotransplantation—what donor genetic modifications may be necessary?”, Xenotransplantation, 2012, 19:144-158. [cited by applicant]
Li et al., “Rosa26-targeted swine models for stable gene over-expression and Cre-mediated lineage tracing,” Cell Research, 2014, 24:501-504. [cited by applicant]
Mohiuddin et al., “Chimeric 2C1OR4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.ACD46.hTBM pig-to-primate cardiac xenograft,” Nature Communications, vol. 7:11138, Apr. 5, 2016, pp. 1-10. [cited by applicant]
Cooper et al., “Experimental Pig Heart Xenotransplantation—Recent Progress and Remaining Problems,” Ann. Thorac. Surg., Apr. 2019, 107(4):989-992. [cited by applicant]
d'Apice et al., “Xenotransplantation: The next generation of engineered animals,” Transplant Immunology, 2009, 21:111-115. [cited by applicant]
Fischer et al., “Multi-transgenic pigs for xenotransplantation,” Xenotransplantation, 2013, 20:64; Berlin Symposium on Xenotransplantation 2012—Abstracts. [cited by applicant]
Fisicaro et al., “Efficient co-expression of multiple graft-protective transgenes using the 2A system,” Xenotransplantation, 2007, 14(4):383, Abstract 106.3. [cited by applicant]
Hinrichs et al., “Inactivation of the GHR gene—a strategy to overcome excess growth of orthotopic pig-to-baboon cardiac xenografts?”, Xenotransplantation, 2017, 24(e12328):39-40, Abstract O.6.2, Abstracts of the 14th Co… [cited by applicant]
Hurh et al., “Expression Analysis of Combinatorial Genes Using a Bi-Cistronic T2A Expression System in Porcine Fibroblasts,” PLoS One, Jul. 2013, 8(7):e70486, 1-11. [cited by applicant]
Phelps et al., “Production and characterization of transgenic pigs expressing porcine CTLA4-lg,” Xenotransplantation, Nov-Dec. 2009, 16(6):477-485. [cited by applicant]
International Search Report and Written Opinion for PCT/US2016/051126 issued Feb. 7, 2017. [cited by applicant]
Deng, W et al. Use of a 2A Peptide for Generation of Multi-Transgenic Pigs through a Single Round of Nuclear Transfer. PLos One, May 13, 2011, vol. 5, No. 5; pp. 1-9; p. 1, col. 2, 2 [cited by applicant]
Estrada, J.L. et al. Evaluation of Human and Non-Human Primate Antibody Binding to Pig Cells Lacking GGTA1/CMAH/b4GaINT2 genes; Xenotransplantation; Mar. 1, 2015; vol. 22, pp. 194-202; doi: 10.1111/xen.12161; Figure 4; … [cited by applicant]
Hai, T. et al. One-Step Generation of Knockout Pigs by Zygote Injection of CRISPR/Cas System; Cell Research; Jan. 31, 2014; vol. 24, pp. 372-375; doi: 10.1038/cr.2014.1; p. 372, 1str column, 2 [cited by applicant]
Ulrichts, H. et al. Shielding of the Al Doman by the D D3 Domains of von Willebrand Factor Mod-ulates its Interaction with Platelet Glycoprotein Ib-IX-V*; The Journal of Biological Chemistry; Feb. 24, 2006; vol. 281, No… [cited by applicant]