US 12,127,536 B2
Humanized M-CSF mice
Andrew J. Murphy, Croton-on-Hudson, NY (US); Sean Stevens, San Diego, CA (US); Chozhavendan Rathinam, Yonkers, NY (US); Elizabeth Eynon, New Haven, CT (US); Markus Manz, Zollikon (CH); Richard Flavell, Guilford, CT (US); and George D. Yancopoulos, Yorktown Heights, NY (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US); Yale University, New Haven, CT (US); and Institute for Research in Biomedicine (IRB), Bellinzona (CH)
Filed on Aug. 21, 2020, as Appl. No. 17/000,105.
Application 17/000,105 is a continuation of application No. 15/488,177, filed on Apr. 14, 2017, granted, now 10,785,966.
Application 15/488,177 is a continuation of application No. 14/469,308, filed on Aug. 26, 2014, granted, now 9,655,352, issued on May 23, 2017.
Application 14/469,308 is a continuation of application No. 13/372,787, filed on Feb. 14, 2012, granted, now 8,847,004, issued on Sep. 30, 2014.
Claims priority of provisional application 61/442,946, filed on Feb. 15, 2011.
Prior Publication US 2021/0112791 A1, Apr. 22, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A01K 67/0278 (2024.01); A01K 67/027 (2024.01); A01K 67/0271 (2024.01); A61K 49/00 (2006.01); C12N 15/85 (2006.01); G01N 33/50 (2006.01)
CPC A01K 67/0278 (2013.01) [A01K 67/027 (2013.01); A01K 67/0271 (2013.01); A61K 49/0008 (2013.01); C12N 15/8509 (2013.01); G01N 33/5088 (2013.01); A01K 2207/12 (2013.01); A01K 2207/15 (2013.01); A01K 2217/072 (2013.01); A01K 2217/15 (2013.01); A01K 2227/105 (2013.01); A01K 2267/03 (2013.01); A01K 2267/0337 (2013.01); C12N 2015/8536 (2013.01); G01N 2500/10 (2013.01)] 21 Claims
 
1. A method of isolating a human immune cell, the method comprising:
isolating a human immune cell from a humanized Macrophage Colony Stimulating Factor (M-CSF) mouse,
wherein the mouse comprises an allele comprising a nucleic acid sequence incorporated into the genome of the mouse, which sequence encodes a human M-CSF protein, is operably linked to the endogenous promoter of the mouse M-CSF gene at the mouse M-CSF locus, and replaces some or all of the mouse M-CSF coding sequence at the mouse M-CSF locus,
wherein the only M-CSF expressed by the allele is human M-CSF,
wherein the mouse expresses M-CSF RNA encoded by the nucleic acid sequence in bone marrow, spleen, blood, liver, brain, lung, testis and kidney,
wherein the mouse expresses human M-CSF protein in blood and/or tissue in substantially the same amount as a wild-type mouse expresses mouse M-CSF protein,
wherein the mouse is immunodeficient, and
wherein the mouse comprises human hematopoietic cells.