IL-15-based fusions to IL-12 and IL-18

Patent metadata

Field	Value
Publication number	US-11129883-B2
Application number	US-201815913837-A
Country	US
Kind code	B2
Filing date	Mar 6, 2018
Priority date	Mar 6, 2017
Publication date	Sep 28, 2021
Grant date	Sep 28, 2021

Abstract

The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.

First claim

What is claimed is:

1. An isolated soluble fusion protein complex comprising at least two soluble proteins, wherein
a first soluble protein comprises an interleukin-15 (IL-15) domain and an IL-12 domain, and a second soluble protein comprises an IL-18 domain and a soluble IL-15 receptor alpha sushi-binding domain (IL-15RαSu) fused to a homodimeric immunoglobulin crystallizable fragment (Fc) domain,
wherein the homodimeric immunoglobulin Fc domain comprises two monomers covalently linked by a disulfide bond, and
wherein 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.

2. The soluble fusion protein complex of claim 1 , wherein the IL-12 domain comprises p40 and p35 subunits of IL-12.

3. The soluble fusion protein complex of claim 2 , wherein the p40 and p35 subunits of IL-12 are linked by a flexible polypeptide linker into a single-chain format.

4. The soluble fusion protein complex of claim 3 , wherein the first soluble protein comprises the amino acid sequence set forth in SEQ ID NO: 8.

5. The soluble fusion protein complex of claim 4 , wherein the second soluble protein comprises the amino acid sequence set forth in SEQ ID NO: 6.

6. The soluble protein complex of claim 1 , wherein the first soluble protein complex is covalently linked to the second soluble protein complex by a disulfide bond linking the Fc domain of the first soluble protein complex to the Fc domain of the second soluble protein complex.

7. The soluble fusion protein complex of claim 1 , wherein the first or second soluble protein further comprises a binding domain that binds to a disease antigen and/or an immune checkpoint or signaling molecule.

8. The soluble fusion protein complex of claim 7 , wherein the disease antigen is associated with neoplasia or infectious disease.

9. An isolated soluble fusion protein complex comprising at least two soluble proteins, wherein
a first soluble protein comprises an IL-15 domain and an IL-18 domain, and a second soluble protein comprises an IL-12 domain and a soluble IL-15RαSu fused to a homodimeric immunoglobulin Fc domain,
wherein the homodimeric immunoglobulin Fc domain comprises two monomers covalently linked by a disulfide bond, and
wherein 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.

10. The soluble fusion protein complex of claim 9 , wherein the IL-12 domain comprises p40 and p35 subunits of IL-12.

11. The soluble fusion protein complex of claim 10 , wherein the p40 and p35 subunits of IL-12 are linked by a flexible polypeptide linker into a single-chain format.

12. The soluble fusion protein complex of claim 11 , wherein the first soluble protein comprises the amino acid sequence set forth in SEQ ID NO: 4.

13. The soluble fusion protein complex of claim 12 , wherein the second soluble protein comprises the amino acid sequence set forth in SEQ ID NO: 2.

14. The soluble protein complex of claim 9 , wherein the first soluble protein is covalently linked to the second soluble protein by a disulfide bond linking an Fc domain of the first soluble protein to an Fc domain of the second soluble protein.

Assignees

• Altor Bioscience Llc

Inventors

• Marcus Warren D
• Newman Robert
• Liu Bai
• You Lijing
• Kong Lin
• Rhode Peter
• Wong Hing C

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• C07K14/7155

  for interleukins [IL] · CPC title

• C07K14/54

  Interleukins [IL] · CPC title

• C07K14/5443 Primary

  IL-15 · CPC title