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Polynucleotides encoding rodent antibodies with human idiotypes and animals comprising same

A polynucleotide and rodent technology, applied in the field of polynucleotides, can solve the problems of low efficiency and disappointing expression level of antigen-specific fully human IgG

Active Publication Date: 2015-10-21
欧莫诺艾比公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, in many laboratories, transgenic constructs with incomplete 3'E regions, often providing only hs1,2 elements, resulted in disturbing expression in transgenic mice even when the endogenous IgH locus was knocked out. level of expression of disappointment
This may be one reason why the generation of antigen-specific fully human IgG from genetically engineered mice has so far been inefficient

Method used

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  • Polynucleotides encoding rodent antibodies with human idiotypes and animals comprising same
  • Polynucleotides encoding rodent antibodies with human idiotypes and animals comprising same
  • Polynucleotides encoding rodent antibodies with human idiotypes and animals comprising same

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Embodiment Construction

[0099] In mice transgenic for human immunoglobulin (Ig) loci, the suboptimal efficacy of delivery of fully human antibodies has been attributed to imperfect interactions between the constant regions of human membrane IgH chains and the mouse cell signaling machinery interaction. To avoid this problem, we describe here a humanized rat strain (OmniRat TM ), which carry a chimeric human / rat IgH locus [comprising 22 human V H , all people D and J H Segment, in native configuration but linked to rat C H locus] along with the fully human light chain loci [12 Vκ linked to Jκ-CK and 16 Vλ linked to Jλ-Cλ]. Silencing of the endogenous rat Ig locus by designer zinc finger nucleases. After immunization, OmniRat performed as efficiently as normal rats in producing high-affinity serum IgG. Monoclonal antibodies comprising fully human variable regions with sub-nanomolar antigen affinity and carrying a wide range of somatic mutations can be readily obtained—similar to the yield of conve...

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Abstract

The invention relates to polynucleotides, particularly chimeric polynucleotides useful for optimal production of functional immunoglobulins with human idiotypes in rodents. The invention further relates to rodents comprising such polynucleotides.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to United States Provisional Patent Application U.S.S.N. 61 / 737,371 filed December 14, 2012. This application is expressly incorporated herein by reference in its entirety. field of invention [0003] The present invention relates to polynucleotides, particularly chimeric polynucleotides, useful for producing immunoglobulins with a human idiotype in rodents. The invention also relates to rodent cells comprising such polynucleotides. [0004] Reference Sequence Listing [0005] In this patent document, the sequence listing is provided in a txt file created on December 12, 2012 (size 3MB) and named "189314-US_ST25.txt". The content of this document is incorporated herein by reference in its entirety. Background of the invention [0006] Human monoclonal antibodies have proven invaluable in therapeutic applications as conventional sized IgG, single chain or domain modules 1,2 . Despi...

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01K67/027C07K16/00C12N15/85
CPCC07K16/00A01K67/0275A01K67/0278A01K2227/105A01K2267/01C07K2317/24C07K2317/52C07K2317/56C07K2317/64C07K2317/92C12N15/8509C07K16/18C07K16/2863C07K16/2896C07K2317/21C07K2317/565C07K16/461
Inventor M·布鲁格曼R·布洛夫M·J·奥斯伯恩B·马
Owner 欧莫诺艾比公司
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