	US 11,950,578 B2
	ADAM6 mice
Lynn Macdonald, Harrison, NY (US); Sean Stevens, Del Mar, CA (US); Andrew J. Murphy, Croton-on-Hudson, NY (US); and Margaret Karow, Santa Rosa Valley, CA (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Dec. 21, 2020, as Appl. No. 17/129,708.
Application 17/129,708 is a division of application No. 16/059,922, filed on Aug. 9, 2018, granted, now 10,905,109.
Application 16/059,922 is a continuation of application No. 14/600,829, filed on Jan. 20, 2015, granted, now 10,072,095, issued on Sep. 11, 2018.
Application 14/600,829 is a continuation of application No. 14/192,051, filed on Feb. 27, 2014, granted, now 9,932,408, issued on Apr. 3, 2018.
Application 14/192,051 is a continuation of application No. 13/890,519, filed on May 9, 2013, granted, now 8,697,940, issued on Apr. 15, 2014.
Application 13/890,519 is a continuation of application No. 13/404,075, filed on Feb. 24, 2012, granted, now 8,642,835, issued on Feb. 4, 2014.
Claims priority of provisional application 61/595,200, filed on Feb. 6, 2012.
Claims priority of provisional application 61/497,650, filed on Jun. 16, 2011.
Claims priority of provisional application 61/446,895, filed on Feb. 25, 2011.
Prior Publication US 2021/0105985 A1, Apr. 15, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/00 (2006.01); A01K 67/0275 (2024.01); A01K 67/0278 (2024.01); B60H 1/32 (2006.01); C07K 16/22 (2006.01); C07K 16/28 (2006.01); C07K 16/40 (2006.01); C07K 16/46 (2006.01); C12N 9/64 (2006.01); C12N 15/85 (2006.01)

CPC A01K 67/0278 (2013.01) [A01K 67/0275 (2013.01); B60H 1/32281 (2019.05); C07K 16/22 (2013.01); C07K 16/28 (2013.01); C07K 16/2866 (2013.01); C07K 16/40 (2013.01); C07K 16/461 (2013.01); C07K 16/462 (2013.01); C12N 9/6489 (2013.01); C12N 15/8509 (2013.01); A01K 2207/15 (2013.01); A01K 2217/072 (2013.01); A01K 2217/15 (2013.01); A01K 2227/105 (2013.01); A01K 2267/01 (2013.01); C07K 2317/21 (2013.01); C07K 2317/92 (2013.01); C12N 2800/204 (2013.01); C12N 2800/30 (2013.01)]

14 Claims

1. A method of determining a nucleotide sequence encoding a human heavy or light chain variable domain comprising the steps of:

(a) immunizing a genetically modified mouse with an antigen, wherein the mouse:

(i) has a genome that comprises:

(A) one or more human V_Hgene segments, one or more human D_Hgene segments, and one or more human J_Hgene segments operably linked to a mouse heavy chain constant region at an endogenous mouse immunoglobulin heavy chain locus,

(B) one or more human V_Lgene segments and one or more human J_Lgene segments operably linked to a light chain constant region, and

(C) a nucleotide sequence that encodes a mouse ADAM6 protein, which nucleotide sequence is integrated in the genome of the mouse, wherein the mouse ADAM6 protein is expressed in the genetically modified mouse;

(ii) generates antibodies when immunized with the antigen, wherein the antibodies each comprise a heavy chain including a human heavy chain variable domain operably linked to a mouse heavy chain constant domain and a light chain including a human light chain variable domain operably linked to a light chain constant domain; and

(iii) is fertile; and

(b) allowing the genetically modified mouse to mount an immune response to the antigen,

(c) isolating a B cell from the genetically modified mouse that expresses an antibody that specifically binds the antigen, and

(d) determining a human heavy or light chain variable region sequence that encodes a human heavy or light chain variable domain, respectively, of an antibody that specifically binds the antigen and that was generated by the genetically modified mouse.