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US 10,294,287 B2Granted
Molecules that selectively activate regulatory T cells for the treatment of autoimmune diseases
AssigneeDelinia, Inc.
InventorJeffrey Greve
Life of this patent
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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 using a linker. 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.
Claims13
A fusion protein comprising:
- a. a human IL-2 variant protein domain comprising a C125S substitution relative to SEQ ID NO:
- 1 and a substitution selected from the group consisting of:
- N88R, N88G, D20H, Q126L, and Q126F;
- b. a peptide linker domain of from 5 to 30 amino acid residues, wherein the peptide linker domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO:
- 15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 18 and SEQ ID NO:
- 19;
- 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 protein yield of the fusion protein is increased by at least two-fold relative to a fusion protein that comprises the human IL-2 variant protein domain and the IgG Fc protein domain, but does not comprise the peptide linker domain.
10 more elements
A dimeric protein comprising two identical chains, wherein each chain comprises a fusion protein comprising:
- a. a human IL-2 variant protein domain comprising a C125S substitution relative to SEQ ID NO:
- 1 and a substitution selected from the group consisting of:
- N88R, N88G, D20H, Q126L, and Q126F;
- b. a peptide linker domain of from 5 to 30 amino acid residues, wherein the peptide linker domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO:
- 15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 18 and SEQ ID NO:
- 19;
- 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 protein yield of the fusion protein is increased by at least two-fold relative to a fusion protein that comprises the human IL-2 variant protein domain and the IgG Fc protein domain, but does not comprise the peptide linker domain.
10 more elements
A pharmaceutical composition comprising a fusion protein comprising:
- a. a human IL-2 variant protein domain comprising a C125S substitution relative to SEQ ID NO:
- 1 and a substitution selected from the group consisting of:
- N88R, N88G, D20H, Q126L, and Q126F;
- b. a peptide linker domain of from 5 to 30 amino acid residues, wherein the peptide linker domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO:
- 15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 18 and SEQ ID NO:
- 19;
- 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 protein yield of the fusion protein is increased by at least two-fold relative to a fusion protein that comprises the human IL-2 variant protein domain and the IgG Fc protein domain, but does not comprise the peptide linker domain.
10 more elements
A fusion protein comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
- 4, SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, SEQ ID NO:
- 10, SEQ ID NO:
- 20, SEQ ID NO:
- 21 and SEQ ID NO:
- 31.
5 more elements
Dependencies are inferred from the claim text.