IP Library › Granted Patent US 12,486,335
Granted Patent B2
US 12,486,335 · App. 17/550,839 · Granted Dec 2, 2025

Mice that make VL binding proteins

Inventors: Lynn Macdonald (Harrison, NY); Sean Stevens (Del Mar, CA); Cagan Gurer (Chappaqua, NY); Karolina A. Meagher (Yorktown Heights, NY); Andrew J. Murphy (Croton-on-Hudson, NY)
Assignee: Regeneron Pharmaceuticals, Inc.
C07K16/468A01K67/0275A01K67/0278C07K16/00C07K16/082C07K16/461C12N15/8509A01K2217/072A01K2227/105A01K2267/01C07K2317/14C07K2317/21C07K2317/31C07K2317/56C07K2317/92C12N2015/8518
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Quick Facts
Patent No.
US 12,486,335
App. No.
17/550,839
Granted
Dec 2, 2025
Kind
B2
Abstract

Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.

Claims (13)

1 . A method for making a binding protein comprising

obtaining a nucleotide sequence encoding a Vκ domain from a gene encoding a Vκ domain fused to a C H region from a cell of a mouse,

wherein the germline genome of the mouse comprises an endogenous immunoglobulin (Ig) heavy chain locus modified to comprise a human genomic germline kappa (κ) sequence that comprises:

(i) unrearranged functional human Ig light chain variable κ (hVκ) gene segments and

(ii) all five unrearranged functional human Ig light chain joining κ (hJκ1-hJκ5) gene segments,

wherein the human genomic germline k sequence:

(A) replaces, at the endogenous Ig heavy chain locus, an endogenous genomic sequence comprising endogenous immunoglobulin heavy chain V gene segments, all endogenous immunoglobulin heavy chain D gene segments, and all endogenous immunoglobulin heavy chain J gene segments, and

(B) rearranges in a B cell during B cell development to form a rearranged Ig hVκ/hJκ gene sequence operably linked to an endogenous Ig heavy chain constant region (C H ) nucleic acid sequence at the endogenous Ig heavy chain locus, and

wherein the mouse comprises a CD19 + B cell comprising the rearranged Ig hVκ/hJκ gene sequence operably linked to the endogenous Ig C H nucleic acid sequence,

cloning the nucleotide sequence encoding the Vκ domain in frame with a gene encoding a human C H region to form a human binding protein encoding sequence, and

expressing the human binding protein encoding sequence in a suitable cell.

2 . The method of claim 1 , wherein the mouse is homozygous for the modified endogenous Ig heavy chain locus.

3 . The method of claim 1 , wherein the mouse is heterozygous for the modified endogenous Ig heavy chain locus.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 3, 2025
From: MACDONALD, LYNN; STEVENS, SEAN; GURER, CAGAN; MEAGHER, KAROLINA A.; MURPHY, ANDREW J.
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 070385/0070 →
Continuity (5)
Division 15497043 · Apr 25, 2017
Division 14135510 · Dec 19, 2013
Division 13195951 · Aug 2, 2011
Provisional Application 61369909 · Aug 2, 2010
Related Publication 20220177606A1 · Jun 9, 2022
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