Method of producing xenogenous antibodies using a bovine

• US 7,928,285 B2
• Filed: 06/25/2008
• Issued: 04/19/2011
• Est. Priority Date: 04/22/2004
• Status: Active Grant

• Current Assignee: SAB LLC (W.P. Carey, Inc. (Real Estate))
• Original Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited)
• Inventors: Kuroiwa, Yoshimi, Kasinathan, Poothappillai, Tomizuka, Kazuma, Ishida, Isao, Robl, James M.
• Primary Examiner(s): Kaushal; Sumesh
• Application Number:
  US12/215,085
• Publication Number:
  US 20090222935A1
• Time in Patent Office: 1,028 Days
• Field of Search: None
• US Class Current: 800/4
• 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 2227/101 Bovine
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A01K 2267/02 Animal zootechnically ameliorated
• CPC Class Codes: A01K 2267/0343 Animal model for prion disease
• CPC Class Codes: A01K 67/0271 Chimeric vertebrates, e.g. comprising exogenous cells
• CPC Class Codes: A01K 67/0273 Cloned 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: C07K 2317/00 Immunoglobulins specific features
• 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 15/8771 Bovine embryos

Abstract

In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.

Claims

1. A method of producing xenogenous antibodies, said method comprising the steps of:

(a) providing a transgenic bovine whose genome comprises a homozygous mutation of both alleles of two different unrearranged IgM heavy chain loci, said mutations disrupting IgM heavy chain production and said transgenic bovine producing less than 10% of endogenous IgM heavy chain relative to a control bovine lacking the mutations, wherein said bovine further comprises a nucleic acid encoding all or part of a xenogenous immunoglobulin locus that undergoes rearrangement and expresses a xenogenous immunoglobulin;

(b) administering one or more antigens of interest to said bovine; and

(c) recovering xenogenous antibodies from said bovine.

2. The method of claim 1, wherein said xenogenous antibodies are human antibodies.

3. The method of claim 1, wherein said xenogenous antibodies are recovered from the serum or milk of the bovine.

4. The method of claim 1, wherein said bovine lacks functional IgM heavy chain.

5. The method of claim 1, wherein one of said loci is Igμ

U and one of said loci is Igμ

AY.

6. The method of claim 1, wherein said nucleic acid is contained within a chromosome fragment.