Anti-pdl1, il-15 and tgf-beta receptor combination molecules
AssigneeAltor BioScience Corporation
InventorsQiongzhen Li, Xiaoyun Zhu, Hing C. Wong
Life of this patent
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Abstract
The invention features multi-specific protein complexes with one domain comprising IL-15 or a functional variant, a cytokine receptor or cytokine ligand, and a binding domain specific to a disease antigen, immune checkpoint or signaling molecule.
Claims42
An isolated soluble fusion protein complex comprising at least two soluble proteins, wherein
- a first soluble protein comprises an interleukin-15 (IL-15) polypeptide domain and a second soluble protein comprises a soluble IL-15 receptor alpha sushi-binding domain (IL-15RαSu) fused to an immunoglobulin Fc domain, wherein the immunoglobulin Fc domain is fused or linked to a transforming growth factor-beta receptor type 2 (TGFβRII) domain;
- the first and/or second soluble protein further comprises a binding domain that specifically binds to a disease antigen, immune checkpoint molecule or immune signaling molecule, and
- the IL-15 domain of the first soluble protein binds to the IL-15RαSu domain of the second soluble protein to form a soluble fusion protein complex.
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A soluble fusion complex comprising at least two soluble proteins a first fusion protein and a second fusion protein, wherein:
- the first fusion protein comprises a transforming growth factor-beta receptor type 2 (TGFβRII) dimer comprising a first TGFβRII domain linked to a second TGFβRII domain wherein the TGFβRII dimer is fused to an interleukin-15 (IL-15) polypeptide domain;
- the second fusion protein comprises a soluble IL-15 receptor alpha sushi-binding domain (IL-15RαSu) fused to an immunoglobulin Fc domain;
- wherein the second fusion protein further comprises a binding domain that specifically binds to a disease antigen, immune checkpoint molecule or immune signaling molecule, and
- wherein the IL-15 domain of the first fusion protein binds to the IL-15Rα Su domain of the second fusion protein to form a soluble fusion protein complex.
A soluble fusion complex comprising at least two soluble proteins a first fusion protein and a second fusion protein, wherein:
- the first fusion protein comprises an interleukin-15 (IL-15) polypeptide domain fused to a binding domain that specifically binds to a disease antigen, immune checkpoint molecule or immune signaling molecule;
- the second fusion protein comprises a transforming growth factor-beta receptor type 2 (TGFβRII) dimer comprising a first TGFβRII domain linked to a second TGFβRII domain wherein the TGFβRII dimer and a soluble IL-15 receptor alpha sushi-binding domain (IL-15RαSu) fused to an immunoglobulin Fc domain;
- wherein the first or second TGFβRII domain is fused to the IL-15RαSu domain
- wherein the IL-15 polypeptide domain of the first fusion protein binds to the IL-15RαSu domain of the second fusion protein to form a soluble fusion protein complex.
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A nucleic acid sequence comprising SEQ ID NOS:
- 1, 3, 5, 7, 9, 11, 13, 15, 16, 17, 18, 19 or combinations thereof, or an amino acid sequence comprising SEQ ID NOS:
- 2, 4, 6, 8, 10, 12, 14, 20, 21, 22, 23, 24 or 46, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 or 45, 38, 39 or combinations thereof.
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An isolated soluble fusion protein complex comprising at least two soluble proteins, wherein
- a first soluble protein comprises an interleukin-15 (IL-15) polypeptide domain and a second soluble protein comprises a soluble IL-15 receptor alpha sushi-binding domain (IL-15RαSu) fused to an immunoglobulin Fc domain, wherein the immunoglobulin Fc (IgG Fc) domain is fused or linked to a glycosylate or an aglycosylated transforming growth factor-beta receptor type 2 (TGFβRII) domain;
- the first and/or second soluble protein further comprises a binding domain that specifically binds to a disease antigen, immune checkpoint molecule or immune signaling molecule, and
- the IL-15 domain of the first soluble protein binds to the IL-15RαSu domain of the second soluble protein to form a soluble fusion protein complex.
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42-64. (canceled)
Dependencies are inferred from the claim text.