IL-2 variants for the treatment of psoriasis
AssigneeDelinia, Inc.
InventorJeffrey Greve
Life of this patent
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Abstract
This disclosure provides for a method for treating a condition by administering to a subject in need thereof a therapeutically-effective amount of a compound that comprises an IL-2 receptor-binding moiety. The methods described in the present disclosure provide enhanced pharmacokinetic profiles. The disclosure also provides methods for treating autoimmune disease comprising administering a therapeutically-effective amount of a fusion protein comprising an IL-2 variant protein.
Claims13
A method for treating an autoimmune disease in a subject in need thereof, the method comprising administering to the subject at least two doses of a pharmaceutical composition comprising a therapeutically-effective amount of a fusion protein comprising:
- a. a human IL-2 variant protein domain comprising a substitution selected from the group consisting of T3A and C125S relative to the amino acid sequence of SEQ ID NO:
- 2, and a substitution selected from the group consisting of D20H, N88I, N88G, N88R, Q126L, and Q126F relative to the amino acid sequence of SEQ ID NO:
- 2;
- b. a peptide linker domain comprising the amino acid sequence (GGGGS)n (SEQ ID NO:
- 8), wherein n is 1, 2, 3 or 4;
- 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 the composition is administered to the subject at a dosing frequency from once every week to once every month and at a dose of 20 μg/kg to 2 mg/kg,
- wherein administration of the pharmaceutical composition to the subject increases the ratio of regulatory T cells to conventional T cells (Treg/Tconv) by at least 2.9-fold six days after administration relative to the Treg/Tconv ratio in the subject before treatment with the pharmaceutical composition,
- and wherein the autoimmune disease is selected from the group consisting of psoriasis, ulcerative colitis, and Crohn's disease.
A method for increasing proliferation of regulatory T cells in a subject in need thereof, the method comprising administering to the subject at least two doses of a pharmaceutical composition comprising a therapeutically effective amount of a fusion protein comprising:
- a. a human IL-2 variant protein domain comprising a substitution selected from the group consisting of T3A and C125S relative to the amino acid sequence of SEQ ID NO:
- 2, and a substitution selected from the group consisting of D2OH, N88I, N88G, N88R, Q126L, and Q126F relative to the amino acid sequence of SEQ ID NO:
- 2;
- b. a peptide linker domain comprising the amino acid sequence (GGGGS)n (SEQ ID NO:
- 8), wherein n is 1, 2, 3 or 4;
- 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 the composition is administered to the subject at a dosing frequency from once every week to once every month and at a dose of 20 μg/kg to 2 mg/kg, and wherein administration of the pharmaceutical composition to the subject increases the ratio of regulatory T cells to conventional T cells (Treg/Tconv) by at least 2.9-fold six days after administration relative to the Treg/Tconv ratio in the subject before treatment with the pharmaceutical composition.
A method for maintaining the ratio of regulatory T cells (Treg) to conventional T cells (Tconv) at a level of at least 0.2 in a subject, the method comprising administering to the subject at least two doses of a pharmaceutical composition comprising a therapeutically effective amount of a fusion protein comprising:
- a. a human IL-2 variant protein domain comprising a substitution selected from the group consisting of T3A and C125S relative to the amino acid sequence of SEQ ID NO:
- 2, and a substitution selected from the group consisting of D2OH, N88I, N88G, N88R, Q126L, and Q126F relative to the amino acid sequence of SEQ ID NO:
- 2;
- b. a peptide linker domain comprising the amino acid sequence (GGGGS)n (SEQ ID NO:
- 8), wherein n is 1, 2, 3 or 4;
- 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 the composition is administered to the subject at a dosing frequency from once every week to once every month and at a dose of 20 μg/kg to 2 mg/kg,
- and wherein administration of the pharmaceutical composition to the subject increases the Treg/Tconv ratio by at least 2.9-fold six days after administration relative to the Treg/Tconv ratio in the subject before treatment with the pharmaceutical composition.
Dependencies are inferred from the claim text.