Transgenic non-human animals for producing heterologous and chimeric antibodies

• US 20060026703A1
• Filed: 12/10/2004
• Published: 02/02/2006
• Est. Priority Date: 08/29/1990
• Status: Abandoned Application

• Current Assignee: Genpharm Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Genpharm International Inc (Bristol-Myers Squibb Company)
• Inventors: Kay, Robert M., Lonberg, Nils
• Application Number:
  US11/009,769
• Publication Number:
  US 20060026703A1
• Time in Patent Office: Days
• US Class Current: 800/18
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• 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 67/0276 Knock-out vertebrates
• 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 16/462 Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic

Abstract

The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Claims

1. A transgenic mouse comprising an unrearranged human heavy chain immunoglobulin variable region,

wherein the variable region comprises multiple human V_H gene segments, multiple human D gene segments, multiple human J_H gene segments, and

wherein B lymphocytes of the transgenic mouse express an antibody comprising a human immunoglobulin heavy chain variable region.

2. The transgenic mouse according to claim 1 wherein the transgenic mouse further comprises an unrearranged human light chain immunoglobulin variable region.

3. The transgenic mouse according to claim 2 wherein the light chain variable region comprises multiple human V_L gene segments and multiple human J_L gene segments.

4. The transgenic mouse according to claim 1 wherein the antibody comprises a human light chain.

5. The transgenic mouse according to claim 4 wherein the human light chain comprises a kappa constant region.

6. The transgenic mouse according to claim 4 wherein the human light chain comprises a lambda constant region.

7. The transgenic mouse according to claim 1 wherein the heavy chain immunoglobulin variable region is encoded on a nucleic acid molecule of about 25 Kb to about 150 Kb.

8. The transgenic mouse according to claim 1 wherein the immunoglobulin heavy chain comprises a human mu constant region.

9. The transgenic mouse according to claim 1 wherein the immunoglobulin heavy chain comprises a human gamma constant region.

10. The transgenic mouse according to claim 1 wherein the human heavy chain immunoglobulin variable region further comprises a cis-acting transcriptional regulatory region containing at least one promoter.

11. A transgenic mouse comprising an unrearranged human light chain immunoglobulin variable region,

wherein the variable region comprises multiple human V_L gene segments, multiple human J_L gene segments, and

wherein B lymphocytes of the transgenic mouse express an antibody comprising a human immunoglobulin light chain variable region.

12. The transgenic mouse according to claim 11 wherein the transgenic mouse further comprises an unrearranged human heavy chain immunoglobulin variable region.

13. The transgenic mouse according to claim 12 wherein the heavy chain variable region comprises multiple human V_L gene segments, multiple human D gene segments and multiple human J_L gene segments.

14. The transgenic mouse according to claim 12 wherein the transgenic mouse further comprises a heavy chain constant region.

15. The transgenic mouse according to claim 14 wherein the heavy chain constant region comprises a mu constant region and a gamma constant region.

16. The transgenic mouse according to claim 11 wherein the antibody comprises a human heavy chain.

17. The transgenic mouse according to claim 11 wherein the light chain comprises a kappa constant region.

18. The transgenic mouse according to claim 11 wherein the light chain comprises a lambda constant region.

19. The transgenic mouse according to claim 11 wherein the light chain immunoglobulin variable region is encoded on a nucleic acid molecule of about 25 Kb to about 150 Kb.

20. The transgenic mouse according to claim 11 wherein the human heavy chain immunoglobulin variable region further comprises a cis-acting transcriptional regulatory region containing at least one promoter.