Genetically modified non-human animals and methods for producing heavy chain-only antibodies
AssigneeAkeagen, Inc.
InventorsLibin Cui, Xiaolin Sun
Life of this patent
Estimating the term…
Abstract
The present application provides genetically modified non-human animals and methods for producing heavy chain-only antibodies (HcAbs), wherein the genetically modified non-human animal comprises a germline genome comprising an engineered immunoglobulin heavy chain (IgH) allele at an endogenous IgH locus, wherein the engineered IgH allele lacks functional gene segments encoding CH1 domains of all endogenous IgG subclasses. In some embodiments, a genetically modified mouse is provided, comprising an engineered IgH allele that lacks a functional endogenous gene segment encoding Cγ3, Cγ1, Cγ2b and CH1 exon of Cγ2c. Further provided are HcAbs or derivatives thereof produced by the genetically modified non-human animals.
Claims11
A method of producing a heavy chain-only antibody (HcAb) that specifically binds to an antigen of interest, comprising:
- (a) immunizing a genetically modified non-human animal with the antigen, wherein the genetically modified non-human animal comprises a germline genome comprising an engineered immunoglobulin heavy chain (IgH) allele at an endogenous IgH locus, wherein the engineered IgH allele lacks endogenous gene segments encoding functional CH1 domains of all endogenous IgG subclasses, wherein the genetically modified non-human animal is a mouse or a rat, and wherein the engineered IgH allele lacks an endogenous gene segment comprising Cγ3, Cγ1, Cγ2b and CH1 exon of Cγ2c;
- and
- (b) obtaining a HcAb that specifically binds to the antigen from the immunized genetically modified non-human animal, thereby producing the HcAb.
A B cell isolated from a genetically modified non-human animal, wherein the genetically modified non-human animal comprises a germline genome comprising an engineered immunoglobulin heavy chain (IgH) allele at an endogenous IgH locus, wherein the engineered IgH allele lacks endogenous gene segments encoding functional CH1 domains of all endogenous IgG subclasses, wherein the genetically modified non-human animal is a mouse or a rat, and wherein the engineered IgH allele lacks an endogenous gene segment comprising Cγ3, Cγ1, Cγ2b and CH1 exon of Cγ2c.
Dependencies are inferred from the claim text.