Interleukin-18 variants and methods of use
AssigneeYale University
InventorsAaron Ring, Ting Zhou, Suzanne Fischer
Life of this patent
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Abstract
The present invention provides compositions and methods comprising an activator of interleukin-18 (IL-18) activity for use in therapeutic and non-therapeutic applications. The activator provides IL-18 signaling activity even in the presence of an inhibitory molecule 5 such as IL-18 binding protein (IL-18BP).
Claims28
A method comprising administering to a subject a composition comprising a modified interleukin 18 (IL-18) polypeptide conjugated, with or without a linker, to an anti-PD-1 antibody, wherein the modified IL-18 polypeptide comprises an amino acid sequence having 93% or more sequence identity with the wild-type (WT) IL-18 sequence as set forth in SEQ ID NO:
- 30 and at least three mutations, relative to WT human IL-18 as set forth in SEQ ID NO:30, that reduce binding to IL-18 binding protein (IL-18BP) as compared to WT IL-18 as set forth in SEQ ID NO:
- 30, wherein the at least three mutations comprise at least one substitution at a position selected from:
- Methionine-51, Lysine-53, Serine-55, Glutamine-56, Proline-57, Glycine-59, and Methionine-60.
A method comprising administering to a subject a composition comprising a nucleic acid encoding a modified interleukin 18 (IL-18) polypeptide fused, with or without a linker, to an anti-PD-1 antibody, wherein the modified IL-18 polypeptide comprises an amino acid sequence having 93% or more sequence identity with the wild-type (WT) IL-18 sequence as set forth in SEQ ID NO:
- 30 and at least three mutations, relative to WT human IL-18 as set forth in SEQ ID NO:30, that reduce binding to IL-18 binding protein (IL-18BP) as compared to WT IL-18 as set forth in SEQ ID NO:
- 30, wherein the at least three mutations comprise at least one substitution at a position selected from:
- Methionine-51, Lysine-53, Serine-55, Glutamine-56, Proline-57, Glycine-59, and Methionine-60.
Dependencies are inferred from the claim text.