Animals, repertoires & methods
AssigneeKymab Limited
InventorsAllan Bradley, E-Chiang Lee
Life of this patent
Estimating the term…
Abstract
The present invention is directed to the concept of sectoring antibody gene segment repertoires in order to enable the development of novel, synthetic antibody chain repertoires not seen in nature. The present invention is also directed to the realisation of the inventors that sectoring can also alter gene segment expression by providing new arrangements of gene segment clusters relative to other gene segments and regulatory elements in transgenic immunoglobulin loci, thereby providing for new synthetic antibody chain sequence repertoires. The invention also relates to gene segment inversion.
Claims24
1-145. (canceled)
A mouse, wherein the genome of said mouse comprises one or more recombinant immunoglobulin light chain loci, and one or more recombinant immunoglobulin heavy chain loci,
- (a) said recombinant immunoglobulin heavy chain locus comprising one or more human V gene segments, one or more human D gene segments and one or more human J gene segments upstream of one or more constant regions comprising an endogenous C segment;
- and
- (b) said recombinant immunoglobulin light chain locus comprising a human Vλ gene segment repertoire and one or more human Jλ gene segments upstream of one or more light chain constant regions comprising an endogenous C segment;
- wherein following rearrangement, said recombinant immunoglobulin light chain locus expresses light chains comprising variable region sequences derived from said human Vλ gene segment repertoire,
- wherein endogenous kappa light chain expression has been substantially inactivated, and
- wherein endogenous heavy chain expression has been substantially inactivated.
A mouse, wherein the genome of said mouse comprises one or more recombinant immunoglobulin light chain loci, and one or more recombinant immunoglobulin heavy chain loci,
- (a) said recombinant immunoglobulin heavy chain locus comprising one or more human V gene segments, one or more human D gene segments and one or more human J gene segments upstream of one or more heavy chain constant regions comprising an endogenous C segment;
- and
- (b) said recombinant immunoglobulin light chain locus comprising a human Vλ gene segment repertoire and one or more human Jλ gene segments upstream of one or more light chain constant regions comprising an endogenous C segment;
- (c) wherein the human Vλ gene segment repertoire comprises human lambda chain locus distal Vλ gene cluster gene segments, and wherein human lambda locus proximal Vλ. gene cluster gene segments are not present between said distal Vλ gene cluster gene segments and the human Jλ gene segments in the lambda chain locus of the mouse:
- wherein following rearrangement, said recombinant immunoglobulin light chain locus expresses light chains comprising variable region sequences derived from said human Vλ gene segment repertoire,
- wherein the endogenous kappa light chain expression has been substantially inactivated, and
- wherein endogenous heavy chain expression has been substantially inactivated.
Dependencies are inferred from the claim text.