# US 11,896,648 B2 · Interleukin-2 variant proteins fused to human IgG4 Fc and uses thereof

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- Number: US 11,896,648 B2
- Document ID: US11896648B2
- Status: Granted
- Kind: B2
- Application number: 17/506,483
- Filed: 2021-10-20
- Published: 2022-04-28
- Granted: 2024-02-13
- Earliest claimed: 2020-10-22
- Assignees: Gilead Sciences, Inc.
- Applicants: Gilead Sciences, Inc.
- Inventors: Manuel Baca; Sarah A. Gilmore; Hassan Javanbakht; Prasenjit K. Mukherjee
- Web page: https://patentgrep.com/patent/US11896648B2

## CPC

- A61K 38/2013: {IL-2}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 31/12: Antivirals
- A61P 31/20: for DNA viruses
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- C07K 14/55: IL-2
- 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 2319/00: Fusion polypeptide
- C07K 2319/02: containing a signal sequence
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Provided are serum half-life extended-IL-2 variant (IL-2v) heterodimers having reduced binding to the IL2Rα (CD25) subunit. In particular, Fc-IL-2v heterodimers are provided and methods for making and using, e.g. for enhancing an immune response, e.g. in the prevention and treatment of viral infections and cancer.

## Claims

### Claim 1

A heterodimer comprising a human IgG4 Fc-IL-2v fusion protein comprising (i) a first amino acid sequence of SEQ ID NO: 114 comprising a first Fc domain; and (ii) a second Fc domain comprising an amino acid sequence of SEQ ID NO: 46.

### Claim 2 (depends on 1)

The heterodimer of claim 1, wherein the fusion protein comprising the first Fc domain comprises a first N-terminal signal peptide or leader sequence and the second Fc domain comprises a second N-terminal signal peptide or leader sequence.

### Claim 3 (depends on 1)

The heterodimer of claim 1, wherein the heterodimer does not specifically bind any antigen other than an Fc receptor or a complex of interleukin 2 receptor subunit beta (IL-2RB; CD122) and interleukin 2 receptor subunit gamma (IL-2RG; CD132).

### Claim 4 (depends on 1)

The heterodimer of claim 1, wherein the second Fc domain is not fused to an antigen binding domain.

### Claim 5 (depends on 1)

The heterodimer of claim 1, wherein neither the first Fc domain nor the second Fc domain is fused to an antigen binding domain.

### Claim 6 (depends on 1)

The heterodimer of claim 1, wherein the heterodimer comprises a serum half-life in a human of at least 6, 9, 12, 15, 18, 21, 24 hours, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 days, or longer.

### Claim 7 (depends on 1)

A polynucleotide or multiple polynucleotides encoding the Fc-IL-2v fusion protein and the second Fc domain of the heterodimer of claim 1.

### Claim 8 (depends on 7)

An expression cassette or multiple expression cassettes comprising one or more regulatory sequences operably linked to the polynucleotide or polynucleotides of claim 7.

### Claim 9 (depends on 7)

A vector comprising the polynucleotide or polynucleotides of claim 7.

### Claim 10 (depends on 7)

A cell or population of cells comprising the polynucleotide or polynucleotides of claim 7.

### Claim 11 (depends on 7)

A method of producing an Fc-IL-2 fusion protein heterodimer, the method comprising:
a) culturing a cell or population of cells transformed with the polynucleotide or polynucleotides of claim 7, in a cell culture under conditions sufficient to express the Fc-IL-2 fusion protein heterodimer molecules; and
b) isolating or purifying the Fc-IL-2 fusion protein heterodimer molecules from the cell culture.

### Claim 12 (depends on 1)

A pharmaceutical composition comprising the heterodimer of claim 1, and a pharmaceutically acceptable carrier.

### Claim 13 (depends on 1)

A method of preventing, reducing and/or inhibiting the recurrence, growth, proliferation, migration and/or metastasis of a cancer cell or population of cancer cells in a subject in need thereof, comprising administering to the subject an effective amount of the heterodimer of claim 1, wherein the cancer cell or population of cancer cells are selected from melanoma and colon cancer.

### Claim 14 (depends on 1)

A kit comprising one or more unitary doses of the the heterodimer of claim 1.