US 12,098,179 B2 · Antigenic peptides deriving from urocortin 3 and uses thereof for the diagnosis and treatment of type 1 diabetes

Antigenic peptides deriving from urocortin 3 and uses thereof for the diagnosis and treatment of type 1 diabetes

AssigneesInserm (Institut National De La Sante Et De La Recherche Medicale), Universite De Paris, Centre National de la Recherche Scientifique (CNRS), Ecole Superieure De Physique Et De Chimie Industrielles De La Ville De Paris

InventorsRoberto Mallone, Sergio Gonzalez-Duque, Yann Verdier, Marie-Eliane Azoury, Georgia Afonso, Joëlle Vinh

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Abstract

Despite the notion that human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes (T1D), none of their target epitopes has been demonstrated to be naturally processed and presented by β cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. Urocortin 3 was identified as a novel β-cell antigen, which was processed into HLA-A2- and HLA-A3-restricted epitopes recognized by circulating naive CD8+ T cells in type 1 diabetic and healthy donors. Accordingly, the present invention relates to antigenic peptides derived from urocortin-3 and uses thereof for the diagnosis and treatment of T1D.

Claims7

Dependent claims

A fusion protein comprising a peptide fused to a heterologous polypeptide or an immunoconjugate comprising an antibody fused or conjugated to the peptide, wherein the peptide comprises at least 8 consecutive amino acids of urocortin 3 (UCN3), and wherein:

the at least 8 consecutive amino acids comprise the sequence ranging from the amino acid residue at position 1 to the amino acid residue at position 21 in SEQ ID NO:1 (UCN3), or
the at least 8 consecutive amino acids comprise the sequence ranging from the amino acid residue at position 22 to the amino acid residue at position 71 in SEQ ID NO:1 (UCN3), or
the at least 8 consecutive amino acids comprise the sequence ranging from the amino acid residue at position 119 to the amino acid residue at position 162 in SEQ ID NO:1 (UCN3);
and wherein the peptide is not SEQ ID NO:
2 (MLMPVHFL), SEQ ID NO:
3 (MLMPVHFLL) or SEQ ID NO:
7 (LMPVHFLL).

4 more elements

Dependencies are inferred from the claim text.

Facts

Application

16/981,474Filed 15 Mar 2019

Priority

EP 1830528816 Mar 2018

Published

US 2021/0024603 A128 Jan 2021

Granted

24 Sep 2024

Term ends

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Classification10 codes

C07K 14/57509
Hormones: corticotropin releasing factor [CRF]
C07K 14/70539
Immunoglobulin superfamily: mHC-molecules, e.g. HLA-molecules
C07K 16/26
Against material from animals or humans: against hormones ; against hormone releasing or inhibiting factors
C12N 15/115
DNA or RNA fragments; Modified forms thereof ; Non-coding nucleic acids having a biological activity: aptamers, i.e. nucleic acids binding a…