Molecules that selectively activate regulatory t cells for the treatment of autoimmune diseases
AssigneeDelinia, Inc.
InventorJeffrey Greve
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Abstract
This invention provides for a fusion protein between an IL2αβγ Selective Agonist protein (IL2 Selective Agonist) and a IgG Fc protein. The IL2 Selective Agonist moiety provides a therapeutic activity by selectively activating the IL2αβγ form of the receptor, thus selectively stimulating Tregs. The Fc moiety provides a prolonged circulating half-life compared to the circulating half-life of IL-2 or an IL2SA protein.
Claims21
A fusion protein comprising:
- a. a human IL-2 variant protein domain;
- b. a peptide linker domain;
- and
- c. an IgG Fc protein domain,
- wherein each domain has an amino-terminus (N-terminus) and a carboxy terminus (C-terminus);
- and
- wherein the fusion protein is configured so that the C-terminus of the human IL-2 variant protein domain is fused through a peptide bond to the N-terminus of the peptide linker domain, and the N-terminus of the IgG Fc protein domain is fused through a peptide bond to the C-terminus of the peptide linker domain.
A nucleic acid encoding a fusion protein comprising:
- a. a human IL-2 variant protein domain;
- b. a peptide linker domain;
- and
- c. an IgG Fc protein domain,
- wherein each domain has an amino-terminus (N-terminus) and a carboxy terminus (C-terminus);
- and
- wherein the fusion protein is configured so that the C-terminus of the human IL-2 variant protein domain is fused through a peptide bond to the N-terminus of the peptide linker domain, and the N-terminus of the IgG Fc protein domain is fused through a peptide bond to the C-terminus of the peptide linker domain.
A dimeric protein comprising two identical chains, wherein each chain comprises a fusion protein comprising:
- a. a human IL-2 variant protein domain;
- b. a peptide linker domain;
- and
- c. an IgG Fc protein domain,
- wherein each domain has an amino-terminus (N-terminus) and a carboxy terminus (C-terminus);
- and
- wherein the fusion protein is configured so that the C-terminus of the human IL-2 variant protein domain is fused through a peptide bond to the N-terminus of the peptide linker domain, and the N-terminus of the IgG Fc protein domain is fused through a peptide bond to the C-terminus of the peptide linker domain.
A pharmaceutical composition comprising a fusion protein comprising:
- a. a human IL-2 variant protein domain;
- b. a peptide linker domain;
- and
- c. an IgG Fc protein domain,
- wherein each domain has an amino-terminus (N-terminus) and a carboxy terminus (C-terminus);
- and
- wherein the fusion protein is configured so that the C-terminus of the human IL-2 variant protein domain is fused through a peptide bond to the N-terminus of the peptide linker domain, and the N-terminus of the IgG Fc protein domain is fused through a peptide bond to the C-terminus of the peptide linker domain.
A method for treating an autoimmune disease, the method comprising administering to a subject in need thereof a therapeutically-effective amount of a pharmaceutical composition comprising a fusion protein comprising:
- a. a human IL-2 variant protein domain;
- b. a peptide linker domain;
- and
- c. an IgG Fc protein domain,
- wherein each domain has an amino-terminus (N-terminus) and a carboxy terminus (C-terminus);
- and
- wherein the fusion protein is configured so that the C-terminus of the human IL-2 variant protein domain is fused through a peptide bond to the N-terminus of the peptide linker domain, and the N-terminus of the IgG Fc protein domain is fused through a peptide bond to the C-terminus of the peptide linker domain.
A method of selectively activating human regulatory T cells, the method comprising administering a pharmaceutical composition comprising a fusion protein comprising:
- a. a human IL-2 variant protein domain;
- b. a peptide linker domain;
- and
- c. an IgG Fc protein domain,
- wherein each domain has an amino-terminus (N-terminus) and a carboxy terminus (C-terminus);
- and
- wherein the fusion protein is configured so that the C-terminus of the human IL-2 variant protein domain is fused through a peptide bond to the N-terminus of the peptide linker domain, and the N-terminus of the IgG Fc protein domain is fused through a peptide bond to the C-terminus of the peptide linker domain,
- wherein said pharmaceutical composition is administered at a therapeutically effective dose until human regulatory T cell concentrations reach desired levels.
Dependencies are inferred from the claim text.