# US 10,766,938 B2 · Nucleic acid encoding human IL-2 variant

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- Number: US 10,766,938 B2
- Document ID: US10766938B2
- Status: Granted
- Kind: B2
- Application number: 16/352,249
- Filed: 2019-03-13
- Published: 2019-07-04
- Granted: 2020-09-08
- Earliest claimed: 2016-01-20
- Assignees: Delinia, Inc.
- Applicants: Delinia, Inc.
- Inventors: Jeffrey Greve
- Web page: https://patentgrep.com/patent/US10766938B2

## CPC

- C07K 14/55: IL-2
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G01N 33/505: {involving T-cells}
- A61K 38/00: 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)
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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.

## Claims

### Claim 1

A nucleic acid encoding a fusion protein comprising:
a. a human IL-2 variant protein domain comprising 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 glycine residues, serine residues, or a mixture of glycine and serine residues; 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.

### Claim 2 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 variant protein domain comprises the N88R substitution.

### Claim 3 (depends on 1)

The nucleic acid of claim 1, wherein the peptide linker domain consists of 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.

### Claim 4 (depends on 1)

A plasmid comprising the nucleic acid of claim 1.

### Claim 5 (depends on 1)

A host cell comprising the nucleic acid of claim 1.

### Claim 6 (depends on 5)

The host cell of claim 5, wherein the host cell is a mammalian cell.

### Claim 7 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 variant protein domain further comprises a C125S substitution.

### Claim 8 (depends on 1)

The nucleic acid of claim 1, 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.

### Claim 9 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 variant protein domain selectively activates the IL2Rαβγ receptor complex relative to the IL2Rβγ receptor complex.

### Claim 10

A nucleic acid encoding 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.

### Claim 11 (depends on 10)

A plasmid comprising the nucleic acid of claim 10.

### Claim 12 (depends on 10)

A host cell comprising the nucleic acid of claim 10.

### Claim 13 (depends on 12)

The host cell of claim 12, wherein the host cell is a mammalian cell.