US 10,701,911 B2 · Genetically modified non-human animals and methods relating to complement dependent cytotoxicity

Abstract

The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/BIN, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom IL2rgtm1Wjl/SzJ (NRG) and NOD.Cg-Prkdcscid IL2rgtm1Sug/JicTAc (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice. Methods for assessment of therapeutic antibodies or putative therapeutic antibodies in the genetically modified immunodeficient mice characterized by an intact complement system are provided according to specific aspects of the present invention.

Claims9

Dependent claims

A method of producing a NSG-Hc1 mouse, the method comprising:

outcrossing mice comprising a wild-type Hc1 allele to NOD mice to produce progeny mice;
backcrossing the progeny mice to NOD mice to produce homozygous NOD-Hc1 mice;
mating the homozygous NOD-Hc1 mice with NSG mice to produce F1 offspring heterozygous for a wild type Hc allele (Hc0/Hc1), a Prkdcscid allele, and a Il2rgnull allele;
and
intercrossing the heterozygous F1 offspring to produce a NSG-Hc1 mouse homozygous for the Prkdcscid allele, the IL2rgtm1Wjl allele, and the Hc1 allele.

2 more elements

Dependencies are inferred from the claim text.

Facts

Application

15/736,951Filed 16 Jun 2016 · us provisional application

Priority

16 Jun 2015

Published

US 2018/0184629 A15 Jul 2018

Granted

7 Jul 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

A01K 67/0275
New or modified breeds of vertebrates: genetically modified vertebrates, e.g. transgenic
A01K 67/027
Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals: new or modified breeds of vertebrates
A01K 67/0271
New or modified breeds of vertebrates: chimeric vertebrates, e.g. comprising exogenous cells
A61K 49/0008
Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for…:…

Genetically modified non-human animals and methods relating to complement dependent cytotoxicity

Life of this patent

Genetically modified non-human animals and methods relating to complement dependent cytotoxicity

Life of this patent

Abstract

Claims9