Transgenic animals bearing human Igλ light chain genes

• US 7,435,871 B2
• Filed: 11/27/2002
• Issued: 10/14/2008
• Est. Priority Date: 11/30/2001
• Status: Expired due to Term

• Current Assignee: Amgen Fremont Inc. (Amgen Inc.)
• Original Assignee: Amgen Fremont Inc. (Amgen Inc.)
• Inventors: Green, Larry L., Ivanov, Vladimir
• Primary Examiner(s): WEHBE, ANNE MARIE SABRINA
• Application Number:
  US10/307,231
• Publication Number:
  US 20030217373A1
• Time in Patent Office: 2,148 Days
• Field of Search: 800/18, 800/4, 435/70.21, 435/326
• US Class Current: 800/18
• 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 2217/052 inducing gain of function
• 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 2227/105 Murine
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A01K 2267/0381 Animal model for diseases of the hematopoietic system
• 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 16/24 against cytokines, lymphokines or interferons
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 2800/206 of yeast origin, e.g. YAC, 2u

Abstract

The invention relates to transgenic animals bearing one or more human λ light chain loci. The invention also relates to methods and compositions for making transgenic animals that have incorporated human λ light chain loci. The invention further relates to methods of using and compositions derived from the transgenic animals that have incorporated human λ light chain loci.

Claims

1. A transgenic mouse whose genome comprises a substantially complete human λ

light chain locus comprising V, J, and constant region genes, wherein the mouse comprises YAC yL.

2. The transgenic mouse according to claim 1, wherein said mouse further comprises a human immunoglobulin heavy chain locus comprising V, D, J, and constant region genes or a portion thereof, a human immunoglobulin κ

light chain locus comprising V, J, and constant region genes or a portion thereof or both said human immunoglobulin heavy chain locus or portion thereof and said human immunoglobulin κ

light chain locus or portion thereof.

4. A method for producing a cell line that produces a human monoclonal antibody or a fragment thereof directed to an antigen, comprising:

a) immunizing the transgenic mouse of claim 2 or 3 with said antigen;

b) allowing said transgenic mouse to mount an immune response to said antigen;

c) isolating B lymphocytes from said transgenic mouse;

d) immortalizing said B lymphocytes;

e) creating individual monoclonal populations of said immortalized B-lymphocytes; and

f) screening said immortalized B lymphocytes to identify a cell line that produces an antibody directed to said antigen.

5. A cell line produced by the method according to claim 4.

6. The transgenic mouse of claim 1, comprising an active endogenous lambda light chain locus.

7. The transgenic mouse of claim 2, wherein the human immunoglobulin heavy chain locus is introduced by a YAC.

9. A method for producing a B lymphocyte that produces a human monoclonal antibody or a fragment thereof directed to an antigen, comprising:

a) immunizing the transgenic mouse of claim 2 or 3 with said antigen;

b) allowing said transgenic mouse to mount an immune response to said antigen;

c) isolating B lymphocytes from said transgenic mouse; and

d) screening said B lymphocytes to identify a cell that produces an antibody directed to said antigen.

3. A transgenic mouse whose genome comprises:

a) a substantially inactivated endogenous heavy chain locus;

b) a substantially inactivated endogenous κ

light chain locus;

c) a human heavy chain locus comprising V, D, J, and constant region genes;

d) a human κ

light chain locus comprising V, J, and constant region genes; and

e) a substantially complete human λ

light chain locus comprising V, J, and constant region genes,

wherein the mouse comprises YAC yL.

8. The transgenic mouse of claim 3, wherein the transgenic mouse expresses human Ig-kappa chains and human Ig-lambda chains in a ratio of 60:

40.