# US 8,541,033 B2 · Production of human antibodies using NOD/SCID/γcnull mice

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- Number: US 8,541,033 B2
- Document ID: US8541033B2
- Status: Granted
- Kind: B2
- Application number: 12/620,469
- Filed: 2009-11-17
- Published: 2011-01-13
- Granted: 2013-09-24
- Earliest claimed: 2000-12-01
- Assignees: Central Institute for Experimental Animals
- Applicants: Mamoru Ito; Kimio Kobayashi; Tatsutoshi Nakahata; Koichiro Tsuji; Sonoko Habu; Yoshio Koyanagi; Naoki Yamamoto; Kazuo Sugamura; Kiyoshi Ando; Tatsuji Nomura
- Inventors: Mamoru Ito; Kimio Kobayashi; Tatsutoshi Nakahata; Koichiro Tsuji; Sonoko Habu; Yoshio Koyanagi; Naoki Yamamoto; Kazuo Sugamura; Kiyoshi Ando; Tatsuji Nomura
- Web page: https://patentgrep.com/patent/US8541033B2

## CPC

- C07K 16/18: against material from animals or humans
- A01K 67/027: New or modified breeds of vertebrates
- A01K 67/0271: Chimeric vertebrates, e.g. comprising exogenous cells
- A61K 40/10: characterised by the cell type used
- A61K 40/46: Viral antigens
- A01K 2267/03: Animal model, e.g. for test or diseases
- A01K 2267/0331: Animal model for proliferative diseases
- A01K 2267/0337: Animal models for infectious diseases
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention provides an immunodeficient mouse (NOG mouse) suitable for engraftment, differentiation and proliferation of heterologous cells, and a method of producing such a mouse. This mouse is obtained by backcrossing a C.B-17-scid mouse with an NOD/Shi mouse, and further backcrossing an interleukin 2-receptor γ-chain gene-knockout mouse with the thus backcrossed mouse. It is usable for producing a human antibody and establishing a stem cell assay system, a tumor model and a virus-infection model.

## Claims

### Claim 1

A method of producing a human antibody comprising:
introducing human B-cells, or both human B cells and T-cells, or human stem cells which differentiate into human B-cells or both human B cells and T-cells, into a mouse produced by a method comprising backcrossing a mouse B with a mouse A, wherein said mouse A is a NOD-scid/scid mouse, and wherein said mouse B is an interleukin 2-receptor γ chain gene knockout mouse, wherein said mouse produced by the method retains the human B-cells or both human B cells and T-cells;
immunizing said mouse with an antigen; and
collecting the human antibody produced from the mouse.

### Claim 2

A method of producing an antibody-producing cell line which produces a human antibody, comprising:
introducing human B-cells, or both human B cells and T-cells, or human stem cells which differentiate into human B-cells or both human B cells and T-cells, into a mouse produced by a method comprising backcrossing a mouse B with a mouse A, wherein said mouse A is a NOD-scid/scid mouse, and wherein said mouse B is an interleukin 2-receptor γ chain gene knockout mouse, wherein said mouse produced by the method retains the human B-cells or both human B cells and T-cells;
immunizing said mouse with an antigen;
collecting from the mouse a cell which produced the antibody against the antigen; and
establishing a cell line of the cell.

### Claim 3 (depends on 1)

The method of claim 1, wherein the human B-cells, or both human B cells and T-cells, or human stem cells which differentiate into human B-cells or both human B cells and T-cells, are introduced intravenously.

### Claim 4 (depends on 1)

The method of claim 1, wherein the human stem cells which differentiate into human B-cells or both human B cells and T-cells are CD34+ cells.

### Claim 5 (depends on 1)

The method of claim 1, wherein the human stem cells which differentiate into human B-cells or both human B cells and T-cells are cord blood cells.

### Claim 6 (depends on 2)

The method of claim 2, wherein the human stem cells which differentiate into human B-cells or both human B cells and T-cells are cord blood cells.

### Claim 7 (depends on 2)

The method of claim 2, wherein the antibody-producing cell is collected from the spleen.

### Claim 8 (depends on 2)

The method of claim 2, wherein the antibody-producing cell is collected from a lymph node.