Production of antibodies from transgenic animals

• US 5,545,807 A
• Filed: 08/05/1994
• Issued: 08/13/1996
• Est. Priority Date: 10/12/1988
• Status: Expired due to Term

• Current Assignee: The Babraham Institute
• Original Assignee: Medical Research Council (Government of United Kingdom), The Babraham Institute
• Inventors: Surani, Azim M., Bruggemann, Marianne, Neuberger, Michael S.
• Primary Examiner(s): Ziska, Suzanne E.
• Application Number:
  US08/286,399
• Time in Patent Office: 739 Days
• Field of Search: 800/2, 514/44, 536/23.53
• US Class Current: 800/6
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• 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 67/0278 Knock-in vertebrates, e.g. humanised vertebrates
• CPC Class Codes: C07K 16/461 Igs containing Ig-regions, -domains or -residues form different species
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic

Abstract

Chimaeric or wholly foreign immunoglobulin is obtained from cells or body fluid of a transgenic animal which has had inserted into its germline genetic material that encodes for at least part of an immunoglobulin, of foreign origin or that can rearrange to encode a repertoire of immunoglobulins, i.e. derived from a different animal source. For example, wholly human immunoglobulins may be produced from a transgenic mouse, possibly in response to an immunogen subsequently introduced to the mouse.

Claims

1. A transgenic mouse which has had inserted into its genome DNA comprising human Vh, human Dh, human Jh segments and human mu segments of human immunoglobulins in germline configuration, such that said Vh, Dh, Jh and mu DNA segments in said germline configuration rearrange in said mouse to form a repertoire of immunoglobulins containing portions which correspond to said human DNA segments, and are expressed in said mouse to produce heavy chains, said heavy chains being capable of forming functional heavy chain-light chain immunoglobulins, said immunoglobulins being expressed in an amount allowing for recovery from suitable cells or body fluids of said mouse.

2. A method of producing immunoglobulins to a particular antigen comprising administering said antigen to the transgenic mouse of claim 1, and obtaining said immunoglobulins from the cells or body fluids of said mouse.

3. The method according to claim 2 wherein said immunoglobulins are polyclonal.

4. The method according to claim 2 wherein said immunoglobulins are obtained from the B cells of said mouse.

5. A method for producing a monoclonal antibody comprising immunizing the mouse of claim 1, and isolating the B cells therefrom, fusing said B cells with a suitable myeloma fusion partner to produce hybridomas, culturing said resulting hybridomas under suitable conditions for production of monoclonal antibodies and recovering the produced chimeric mouse-human monoclonal antibodies.