US 12,389,888 B2
Mice expressing a limited immunoglobulin light chain repertoire
John McWhirter, Sanremo (IT); Lynn Macdonald, Harrison, NY (US); Sean Stevens, Del Mar, CA (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 Apr. 23, 2021, as Appl. No. 17/238,710.
Application 17/238,710 is a continuation of application No. 16/530,030, filed on Aug. 2, 2019, granted, now 11,026,407.
Application 16/530,030 is a continuation of application No. 16/128,360, filed on Sep. 11, 2018, granted, now 10,412,940, issued on Sep. 17, 2019.
Application 16/128,360 is a continuation of application No. 15/700,973, filed on Sep. 11, 2017, granted, now 10,167,344, issued on Jan. 1, 2019.
Application 15/700,973 is a continuation of application No. 13/798,455, filed on Mar. 13, 2013, granted, now 9,796,788, issued on Oct. 24, 2017.
Application 13/798,455 is a continuation in part of application No. 13/488,628, filed on Jun. 5, 2012, abandoned.
Application 13/488,628 is a continuation in part of application No. 13/412,936, filed on Mar. 6, 2012, abandoned.
Application 13/412,936 is a continuation in part of application No. 13/093,156, filed on Apr. 25, 2011, abandoned.
Application 13/093,156 is a continuation in part of application No. 13/022,759, filed on Feb. 8, 2011, granted, now 10,143,186, issued on Dec. 4, 2018.
Claims priority of provisional application 61/302,282, filed on Feb. 8, 2010.
Prior Publication US 2021/0315189 A1, Oct. 14, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A01K 67/0278 (2024.01); A01K 67/0275 (2024.01); C07K 16/00 (2006.01); C07K 16/46 (2006.01); C12N 15/85 (2006.01)
CPC A01K 67/0278 (2013.01) [A01K 67/0275 (2013.01); C07K 16/00 (2013.01); C07K 16/462 (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 2317/24 (2013.01); C07K 2317/515 (2013.01)] 12 Claims
 
1. A method of making a mouse, comprising genetically modifying the germline genome of the mouse so that it includes:
a) exactly two unrearranged human immunoglobulin Vκ gene segments and five unrearranged human immunoglobulin Jκ gene segments operably linked to a mouse immunoglobulin light chain constant region sequence at the endogenous kappa light chain loci of the mouse, wherein the two unrearranged human immunoglobulin Vκ gene segments are a human Vκ1-39 gene segment and a human Vκ3-20 gene segment; and
b) one or more unrearranged human immunoglobulin VH gene segments, one or more unrearranged human immunoglobulin DH gene segments, and one or more unrearranged human immunoglobulin JH gene segments operably linked to a mouse immunoglobulin heavy chain constant region sequence at the endogenous heavy chain loci of the mouse;
wherein the unrearranged human immunoglobulin heavy chain and kappa light chain gene segments are capable of rearranging and encoding human immunoglobulin variable domains of an antibody, and wherein the mouse does not comprise endogenous immunoglobulin Vκ or Jκ gene segments that are capable of rearranging to form an immunoglobulin light chain variable region sequence.