US 11,248,027 B2 · Engineered outer domain (eOD) of HIV GP120, mutants and use thereof

Abstract

The present invention relates to engineered outer domain (eOD) immunogens of HIV gp120 and mutants thereof and methods of making and using the same. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity. The mutant eODs bind to neutralizing antibody precursors. The mutant eODs can activate germline precursors on the pathway to eliciting a broadly neutralizing antibody (bnAb) response. The invention also relates to immunized knock-in mice expressing germline-reverted heavy chains. Induced antibodies showed characteristics of bnAbs and mutations that favored binding to near-native HIV-1 gp120 constructs. In contrast, native-like immunogens failed to activate precursors. The invention also relates to rational epitope design that can prime rare B cell precursors for affinity maturation to desired targets.

Claims5

Dependent claims

A non-naturally occurring protein comprising a monomeric engineered outer domain (eOD), wherein the protein comprises SEQ ID NO:

10 (eOD-GT8).

Dependencies are inferred from the claim text.

Facts

Application

15/844,753Filed 18 Dec 2017 · continuation in part

Priority

17 Jun 2015

Published

US 2018/0194809 A112 Jul 2018

Granted

15 Feb 2022

Term ends

Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07K 14/005
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: from viruses
A01K 67/0278
Genetically modified vertebrates, e.g. transgenic: knock-in vertebrates, e.g. humanised vertebrates
A61K 39/12
Medicinal preparations containing antigens or antibodies: viral antigens
A61K 39/21
Viral antigens: retroviridae, e.g. equine infectious anemia virus

Engineered outer domain (eOD) of HIV GP120, mutants and use thereof

Life of this patent

Engineered outer domain (eOD) of HIV GP120, mutants and use thereof

Life of this patent

Abstract

Claims5