Genetic engineering of non-human animals for the production of chimeric antibodies

• US 11,352,444 B2
• Filed: 03/20/2017
• Issued: 06/07/2022
• Est. Priority Date: 03/31/2010
• Status: Active Grant

• Current Assignee: Ablexis LLC
• Original Assignee: Ablexis LLC
• Inventors: Green, Larry, Shizuya, Hiroaki
• Primary Examiner(s): Dahle, Chun W
• Application Number:
  US15/463,752
• Publication Number:
  US 20170188557A1
• Time in Patent Office: 1,905 Days
• Field of Search: None
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/052 inducing gain of function
• CPC Class Codes: A01K 2217/072 maintaining or altering function, i.e. knock in
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A01K 67/0275 Genetically modified vertebrates, e.g. transgenic
• CPC Class Codes: A01K 67/0278 Knock-in vertebrates, e.g. humanised vertebrates
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/461 Igs containing Ig-regions, -domains or -residues form different species
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/51 Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/522 CH1 domain
• CPC Class Codes: C07K 2317/524 CH2 domain
• CPC Class Codes: C07K 2317/526 CH3 domain
• CPC Class Codes: C07K 2317/53 Hinge
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/64 : comprising a combination of variable region and constant region components
• CPC Class Codes: C12N 15/8509 : for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 2510/02 : Cells for production

Abstract

The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.

Claims

1. A chimeric antibody, or antigen-binding fragment thereof, comprising (i) a chimeric immunoglobulin heavy chain comprising a human immunoglobulin heavy chain variable region and a chimeric immunoglobulin heavy chain constant region, wherein the constant region comprises a human CH1 domain, a human upper hinge region, a murine CH2 domain, and a murine CH3 domain and (ii) an immunoglobulin light chain.

2. The chimeric antibody, or antigen-binding fragment thereof, according to claim 1, wherein the CH1 domain isotype is selected from the group consisting of IgM, IgD, IgG1, IgG2, IgG3, IgG4, IgA, and IgE.

3. The chimeric antibody, or antigen-binding fragment thereof, according to claim 1, wherein the upper hinge region isotype is selected from the group consisting of IgM, IgD, IgG1, IgG2, IgG3, IgG4, IgA, and IgE.

4. The chimeric antibody, or antigen-binding fragment thereof, according to claim 1, wherein the immunoglobulin light chain is an immunoglobulin lambda light chain.

5. The chimeric antibody, or antigen-binding fragment thereof, according to claim 1, wherein the immunoglobulin light chain is an immunoglobulin kappa light chain.

6. The chimeric antibody, or antigen-binding fragment thereof, according to claim 1, wherein the immunoglobulin light chain is human.

7. The chimeric antibody, or antigen-binding fragment thereof, according to claim 6, wherein the murine CH2 domain and the murine CH3 domain are mouse.

8. The chimeric antibody, or antigen-binding fragment thereof, according to claim 1, wherein the immunoglobulin light chain is murine.

9. The chimeric antibody, or antigen-binding fragment thereof, according to claim 8, wherein the immunoglobulin light chain is mouse.

10. The chimeric antibody, or antigen-binding fragment thereof, according to claim 4, wherein the murine CH2 domain and the murine CH3 domain are mouse.

11. The chimeric antibody, or antigen-binding fragment thereof, according to claim 5, wherein the murine CH2 domain and the murine CH3 domain are mouse.