Methods and compositions for preventing the onset of type 1 diabetes
View Patent ↗The present invention relates generally to methods and compositions for treatment, prevention, suppression, and/or delaying the onset of type 1 diabetes. More specifically, the present invention relates to the administration of a fusion protein comprising at least one immunoglobulin having one or more diabetogenic epitopes inserted within the variable region, for suspending, preventing or delaying the onset of type 1 diabetes in a pre-diabetic subject.
1. A method of delaying the onset of type 1 diabetes in a pre-diabetic subject, the method comprising administering to the pre-diabetic subject a pharmaceutically acceptable composition comprising at least one soluble immunoglobulin having a variable region and at least one peptide inserted within the variable region, wherein the at least one peptide is GAD2 represented by SEQ ID NO: 3, and wherein the composition is administered to the subject in one or more dosage administrations.
2. The method of claim 1 , wherein the immunoglobulin is human or humanized.
3. The method of claim 1 , wherein the subject is a human subject.
4. The method of claim 1 , wherein administration of the composition to the subject results in down regulation of an autoreactive T cell.
5. The method of claim 1 , wherein the variable region of the immunoglobulin comprises complementarity determining regions CDR1, CDR2, and CDR3 and the peptide is inserted in the CDR3 region.
6. The method of claim 1 , wherein activation of an autoreactive T cell specific for the peptide is substantially reduced or prevented.
7. The method of claim 1 , wherein the soluble composition is capable of binding to at least one Fc receptor.
8. The method of claim 7 , wherein the Fc receptor is a Fcγ receptor.
9. The method of claim 7 , wherein the composition is endocytosed by antigen presenting cells.
10. The method of claim 1 , wherein the subject is insulin autoantibody positive at initiation of the administering step.
11. The method of claim 1 , wherein the subject is glutamate decarboxylase autoantibody positive at initiation of the administering step.
12. The method of claim 1 , wherein upon administration of the composition to the subject, the subject undergoes a dose dependent suspension or delay in the onset of type 1 diabetes.