US 12,433,264 B2
Non-human animals having an engineered immunoglobulin lambda light chain locus
Chunguang Guo, Thornwood, NY (US); Faith Harris, Mamaroneck, NY (US); Vera Voronina, Sleepy Hollow, NY (US); John McWhirter, Hastings-on-Hudson, NY (US); Natasha Levenkova, New York, NY (US); Lynn Macdonald, Harrison, NY (US); Naxin Tu, Pleasantville, NY (US); and Andrew J. Murphy, Croton-on-Hudson, NY (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Sep. 24, 2020, as Appl. No. 17/031,367.
Application 17/031,367 is a division of application No. 15/803,513, filed on Nov. 3, 2017, granted, now 10,820,582.
Claims priority of provisional application 62/567,932, filed on Oct. 4, 2017.
Claims priority of provisional application 62/417,845, filed on Nov. 4, 2016.
Prior Publication US 2021/0029978 A1, Feb. 4, 2021
Int. Cl. A01K 67/027 (2024.01); A01K 67/0278 (2024.01); C07K 16/00 (2006.01); C12N 15/90 (2006.01); C12N 15/85 (2006.01)
CPC A01K 67/0278 (2013.01) [C07K 16/00 (2013.01); C12N 15/907 (2013.01); A01K 2207/15 (2013.01); A01K 2217/05 (2013.01); A01K 2217/072 (2013.01); A01K 2217/075 (2013.01); A01K 2227/105 (2013.01); A01K 2267/01 (2013.01); C07K 2317/14 (2013.01); C07K 2317/24 (2013.01); C12N 2015/8518 (2013.01); C12N 2800/30 (2013.01)] 21 Claims
 
1. A method of producing an antibody, the method comprising:
(a) immunizing a genetically modified mouse with an antigen of interest, which genetically modified mouse has a germline genome comprising an engineered endogenous immunoglobulin λ light chain locus comprising:
(i) one or more human Vλ gene segments,
(ii) one or more human Jλ gene segments, and
(iii) one or more human Cλ gene segments,
wherein (i) and (ii) are operably linked to (iii) and a mouse Cλ gene segment, and wherein the engineered endogenous immunoglobulin λ light chain locus further comprises one or more mouse immunoglobulin λ light chain enhancers (Eλ) and one or more human immunoglobulin λ light chain enhancers (Eλ);
(b) maintaining the genetically modified mouse under conditions sufficient for the genetically modified mouse to produce an immune response to the antigen of interest; and
(c) recovering an antibody from the genetically modified mouse, or a cell thereof, wherein the antibody:
(i) is capable of binding the antigen of interest, and
(ii) comprises an immunoglobulin λ light chain comprising a human λ variable domain and either a human λ constant domain or a mouse λ constant domain.