Transgenic non-human animals for producing chimeric antibodies

• US 8,158,419 B2
• Filed: 09/26/2008
• Issued: 04/17/2012
• Est. Priority Date: 03/09/1994
• Status: Expired due to Fees

• Current Assignee: Medarex Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Medarex Incorporated (Bristol-Myers Squibb Company)
• Inventors: Lonberg, Nils, Kay, Robert M.
• Primary Examiner(s): Wehbe, Anne Marie S
• Application Number:
  US12/239,493
• Publication Number:
  US 20100287629A1
• Time in Patent Office: 1,299 Days
• Field of Search: 435/328, 435/346, 435/355
• US Class Current: 435/328
• 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. An isolated B lymphocyte hybridoma clone wherein the B lymphocyte hybridoma clone expresses an antibody comprising a heavy chain consisting of a human immunoglobulin heavy chain variable region and a mouse immunoglobulin heavy chain gamma constant region, wherein the isolated B lymphocyte hybridoma is derived from a fusion of:

(a) a B lymphocyte from a transgenic mouse, wherein the genome of said transgenic mouse comprises inactivated murine heavy chain variable regions and an unrearranged human heavy chain immunoglobulin variable region operably linked to a mu constant region gene segment, wherein the unrearranged heavy chain variable region comprises multiple human V_H gene segments, multiple human D gene segments, and multiple human J_H gene segments, and wherein the mu constant region is selected from the group consisting of;

(i) a human S-mu sequence and a human or mouse mu coding sequence; and

(ii) a mouse S-mu sequence and a human or mouse mu coding sequence; and

(b) a myeloma cell.

2. The isolated B lymphocyte hybridoma clone of claim 1, wherein the antibody comprising a heavy chain consisting of human immunoglobulin heavy chain variable region and a mouse immunoglobulin heavy chain gamma constant region expressed by said isolated B lymphocyte hybridoma clone binds to a predetermined antigen.