Method to detect autoantibody reactivity for deamidated insulin autoantigen in diabetes

Patent metadata

Field	Value
Publication number	US-2016355564-A1
Application number	US-201615152093-A
Country	US
Kind code	A1
Filing date	May 11, 2016
Priority date	May 11, 2015
Publication date	Dec 8, 2016
Grant date	—

Abstract

Provided herein are epitopes and mimotopes thereof useful in the diagnosis and treatment of type 1 diabetes (T1D), as well as antibodies recognizing such epitopes, and diagnostics, therapeutics, kits, and methods of use thereof.

First claim

1 . A composition comprising a peptide or polypeptide comprising at least 70% sequence identity to a sequence of one of SEQ ID Nos: 101-111.

2 . The composition of claim 1 , wherein the peptide or polypeptide comprises at least one Q to E substitution relative to SEQ ID NO: 2.

3 . The composition of claim 1 , wherein the peptide or polypeptide is pharmaceutically-formulated for administration to a subject for the treatment or prevention of type 1 diabetes.

4 . A method comprising administering of a composition of claim 1 to a subject for the treatment or prevention of type 1 diabetes.

5 . (canceled)

6 . The method of claim 4 , wherein the subject is at risk of developing type 1 diabetes.

7 . The composition of claim 1 , wherein the peptide or polypeptide further comprises a detectable label.

8 . The composition of claim 1 , wherein the peptide or polypeptide is attached to a solid surface.

9 . A method of diagnosing a subject as having type 1 diabetes or of being at increased risk for developing type 1 diabetes comprising contacting a composition of claim 1 with a sample from the subject, and detecting the presence of antibodies in the sample that bind to the peptide or polypeptide.

10 . A composition comprising an antibody or antibody fragment that selectively binds to a peptide with at least 70% sequence identity to a sequence of one of SEQ ID Nos: 101-111.

11 . A method comprising administering of a composition of claim 10 to a subject for the treatment or prevention of type 1 diabetes.

12 . The composition of claim 10 , wherein the antibody or antibody fragment further comprises a detectable label.

13 . The composition of claim 10 , wherein the antibody or antibody fragment is attached to a solid surface.

14 . A method of diagnosing a subject as having type 1 diabetes or of being at increased risk for developing type 1 diabetes comprising contacting a composition of claim 10 with a sample from the subject, and detecting the presence of deamidated insulin in the sample.

15 . A method of treating or preventing type 1 diabetes in a subject comprising interfering with the deamidation of at least one glutamine residue in a pro-insulin of the subject.

16 . The method of claim 15 , wherein the at least one glutamine residue is a C-peptide glutamine.

17 . (canceled)

Assignees

• Univ Northwestern

Inventors

• Jin Jing
• Luo Xunrong
• Aleppo Grazia

Classifications

• C07K14/62 Primary

  Insulins · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K16/26

  against hormones {; against hormone releasing or inhibiting factors} · CPC title

• G01N2800/042

  Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism · CPC title

• G01N2800/50

  Determining the risk of developing a disease · CPC title