Transgenic transchromosomal rodents for making human antibodies

• US 7,041,870 B2
• Filed: 11/30/2001
• Issued: 05/09/2006
• Est. Priority Date: 11/30/2000
• Status: Expired due to Term

• Current Assignee: ER Squibb & Sons LLC (Bristol-Myers Squibb Company)
• Original Assignee: Medarex Incorporated (Bristol-Myers Squibb Company), Kirin Brewery Company Limited (Kirin Holdings Company Limited)
• Inventors: Tomizuka, Kazuma, Ishida, Isao, Halk, Edward L., Lonberg, Nils
• Primary Examiner(s): LI, QIAN JANICE
• Application Number:
  US10/000,433
• Publication Number:
  US 20020199213A1
• Time in Patent Office: 1,621 Days
• Field of Search: 800 13- 25
• US Class Current: 800/13
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• CPC Class Codes: A01K 2217/072 maintaining or altering function, i.e. knock in
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2217/15 Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
• CPC Class Codes: A01K 2217/30 Animal model comprising expression system for selective cell killing, e.g. toxins, enzyme dependent prodrug therapy using ganciclovir
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A01K 67/02 Breeding vertebrates
• 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: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: C07K 14/70535 Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
• 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 16/243 Colony Stimulating Factors
• CPC Class Codes: C07K 16/2812 against CD4
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 2317/14 : Specific host cells or culture conditions, e.g. components, pH or temperature
• 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 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C12N 15/8509 : for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 2015/8518 : expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles
• CPC Class Codes: C12N 5/0635 : B lymphocytes
• CPC Class Codes: C12N 5/163 : one of the fusion partners being a B or a T lymphocyte
• CPC Class Codes: C12P 21/005 : Glycopeptides, glycoproteins
• CPC Class Codes: C12Q 1/6881 : for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
• CPC Class Codes: C12Q 2600/158 : Expression markers

Abstract

The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.

Claims

1. A transgenic mouse comprising two human immunoglobulin loci, wherein one of said human immunoglobulin loci is a human heavy chain locus and the other locus is a human light chain locus;

wherein the human heavy chain locus is carried by transchromosome SC20 and the human light chain locus is carried by a transgene integrated into the genome of said mouse; and

wherein an endogenous mouse heavy chain locus and at least one endogenous mouse light chain locus are inactivated.

2. The transgenic mouse of claim 1, wherein the endogenous mouse heavy chain locus and the endogenous mouse kappa light chain locus are inactivated.

3. The transgenic mouse of claim 1, wherein at least a part of the human light chain locus is cloned into a YAC vector.

4. The transgenic mouse of claim 1, wherein the transgene is the KCo5 transgene.