# US 2014/0157445 A1 · Low affinity fcgr deficient mice

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- Number: US 2014/0157445 A1
- Document ID: US20140157445A1
- Status: Published application
- Kind: A1
- Application number: 14/152,106
- Filed: 2014-01-10
- Published: 2014-06-05
- Earliest claimed: 2009-12-21
- Assignees: Regeneron Pharmaceuticals, Inc.
- Applicants: Regeneron Pharmaceuticals, Inc.
- Inventors: Lynn Macdonald; Naxin Tu; Cagan Gurer; Sean Stevens; Andrew J. Murphy
- Web page: https://patentgrep.com/patent/US20140157445A1

## CPC

- A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure}
- A01K 67/0276: Knock-out vertebrates
- A01K 67/0278: Knock-in vertebrates, e.g. humanised vertebrates
- C07K 14/70535: {Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)}
- G01N 33/5014: {for testing toxicity}
- A01K 2207/15: Humanized animals
- A01K 2217/072: maintaining or altering function, i.e. knock in
- A01K 2217/075: inducing loss of function, i.e. knock out
- A01K 2217/15: Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
- A01K 2227/105: Murine
- A01K 2267/03: Animal model, e.g. for test or diseases
- A01K 2267/0387: Animal model for diseases of the immune system
- 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.

## Claims

### Claim 1

A genetically modified mouse that does not express an endogenous FcγRIIB α-chain, an endogenous FcγRIV α-chain, and an endogenous FcγRIII α-chain.

### Claim 2 (depends on 1)

The mouse of claim 1, wherein the mouse comprises a reduced ability to make an immune response to an antigen as compared to a wild-type mouse with respect to the same antigen.

### Claim 3 (depends on 1)

The mouse of claim 1, wherein the mouse comprises at least a 50% reduction in antibody-dependent cell-mediated cytotoxicity (ADCC).

### Claim 4 (depends on 1)

The mouse of claim 1, wherein the mouse expresses a functional FcR γ-chain.

### Claim 5 (depends on 1)

The mouse of claim 1, wherein the mouse further expresses human CD20.

### Claim 6

A genetically modified mouse comprising a deletion of an endogenous FcγRIIB α-chain gene, an endogenous FcγRIV α-chain gene, and a deletion of an endogenous FcγRIII α-chain gene.

### Claim 7 (depends on 6)

The mouse of claim 6, wherein the mouse comprises a reduced ability to make an immune response to an antigen as compared to a wild-type mouse with respect to the same antigen.

### Claim 8 (depends on 6)

The mouse of claim 6, wherein the mouse comprises at least a 50% reduction in antibody-dependent cell-mediated cytotoxicity (ADCC).

### Claim 9 (depends on 6)

The mouse of claim 6, wherein the mouse comprises a functional FcR γ-chain gene.

### Claim 10 (depends on 6)

The mouse of claim 6, wherein the mouse further comprises a humanized CD20 gene.

### Claim 11

A genetically modified non-human cell comprising a deletion of an endogenous FcγRIIB α-chain gene, an endogenous FcγRIV α-chain gene, and a deletion of an endogenous FcγRIII α-chain gene.

### Claim 12 (depends on 11)

The cell of claim 11, wherein the cell is a mouse cell.

### Claim 13 (depends on 11)

The cell of claim 11, wherein the cell is a rat cell.

### Claim 14 (depends on 11)

The cell of claim 11, wherein the cell comprises a functional FcR γ-chain.

### Claim 15 (depends on 12)

The cell of claim 12, wherein the cell is an embryonic stem (ES) cell.

### Claim 16 (depends on 12)

The cell of claim 12, wherein the cell is a natural killer (NK) cell.

### Claim 17 (depends on 13)

The cell of claim 13, wherein the cell is an ES cell.

### Claim 18 (depends on 11)

The cell of claim 11, wherein the cell comprises a human CD20 gene.

### Claim 19 (depends on 11)

A method of making a genetically modified non-human animal that does not express an endogenous FcγRIIB α-chain, an endogenous FcγRIV α-chain, and an endogenous FcγRIII α-chain, comprising using the cell of claim 11.

### Claim 20 (depends on 15)

A method of making a genetically modified mouse that does not express an endogenous FcγRIIB α-chain, an endogenous FcγRIV α-chain, and an endogenous FcγRIII α-chain, comprising using the cell of claim 15.