# US 12,005,079 B2 · Biologically relevant orthogonal cytokine/receptor pairs

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- Number: US 12,005,079 B2
- Document ID: US12005079B2
- Status: Granted
- Kind: B2
- Application number: 16/953,000
- Filed: 2020-11-19
- Published: 2021-03-11
- Granted: 2024-06-11
- Earliest claimed: 2015-09-11
- Assignees: The Board of Trustees of the Leland Stanford Junior University; University of Washington
- Applicants: The Board of Trustees of the Leland Stanford Junior University; University of Washington
- Inventors: Kenan Christopher Garcia; Jonathan Sockolosky; Lora Picton
- Web page: https://patentgrep.com/patent/US12005079B2

## CPC

- A61K 38/2013: {IL-2}
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 38/1793: {for cytokines; for lymphokines; for interferons}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/4217: {Receptors for interleukins [IL]}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 14/55: IL-2
- C12N 5/0636: {T lymphocytes}
- C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]}
- C12N 15/1034: {Isolating an individual clone by screening libraries}
- A61K 2039/5156: {expressing foreign proteins}
- A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
- C12N 2740/10043: viral genome or elements thereof as genetic vector
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Engineered orthogonal cytokine receptor/ligand pairs, and methods of use thereof, are provided.

## Claims

### Claim 1

A nucleic acid encoding an engineered human IL-2 polypeptide, which comprises amino acid substitutions, numbered relative to reference SEQ ID NO:4:
E15S, E15T, E15Q, or E15H;
H16Q;
L19V or L19I;
D20T, D20S, D20L or D20M; and
M23L, M23S, M23V, M23A, or M23T;
and optionally comprises Q22K, Q22N, R81D, R81Y, T51I or a combination thereof.

### Claim 2 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide comprises amino acid substitution Q22K.

### Claim 3 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide comprises amino acid substitution T51I.

### Claim 4 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide comprises amino acid substitution R81D or R81Y.

### Claim 5 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide comprises amino acid substitutions Q22K and M23A.

### Claim 6 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide comprises amino acid substitutions M23Q, R81D and T51I.

### Claim 7 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide comprises amino acid substitutions M23Q and R81Y.

### Claim 8 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide comprises amino acid substitution M23A.

### Claim 9

A nucleic acid encoding an engineered human IL-2 polypeptide, which comprises a set of amino acid substitutions, numbered relative to reference SEQ ID NO:4:
E15S;
H16Q;
L19V;
D20L;
M23A; and
Q22K.

### Claim 10 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide comprises a set of amino acid substitutions, numbered relative to reference SEQ ID NO:4:
E15S;
H16Q;
L19V;
D20L;
M23Q;
R81D; and
T51I.

### Claim 11 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide comprises a set of amino acid substitutions, numbered relative to reference SEQ ID NO:4:
E15S;
H16Q;
L19V;
D20L;
M23Q;
and R81Y.

### Claim 12 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide comprises a set of amino acid substitutions, numbered relative to reference SEQ ID NO:4:
E15S;
H16Q;
L19V;
D20L; and
M23A.

### Claim 13 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide is fused to an Fc domain of IgG, or albumin.

### Claim 14 (depends on 1)

The nucleic acid of claim 1, wherein the human IL-2 polypeptide binds to and activates an orthogonal human CD122 protein.

### Claim 15 (depends on 1)

The nucleic acid of claim 1, wherein the nucleic acid is RNA.

### Claim 16 (depends on 1)

The nucleic acid of claim 1, wherein the nucleic acid is DNA.

### Claim 17 (depends on 1)

An expression vector comprising the nucleic acid of claim 1.

### Claim 18 (depends on 17)

The expression vector of claim 17, wherein the vector is a viral vector.

### Claim 19 (depends on 17)

The expression vector of claim 17, wherein the vector is a plasmid vector.

### Claim 20 (depends on 17)

The expression vector of claim 17, wherein the vector is an integrating vector.

### Claim 21 (depends on 1)

A cell genetically engineered to comprise the nucleic acid of claim 1.

### Claim 22 (depends on 9)

The nucleic acid of claim 9, wherein the human IL-2 polypeptide binds to and activates an orthogonal human CD122 protein.

### Claim 23 (depends on 22)

The nucleic acid of claim 22, wherein the nucleic acid is RNA.

### Claim 24 (depends on 22)

The nucleic acid of claim 22, wherein the nucleic acid is DNA.

### Claim 25 (depends on 22)

An expression vector comprising the nucleic acid of claim 22.

### Claim 26 (depends on 25)

The expression vector of claim 25, wherein the vector is a viral vector.

### Claim 27 (depends on 25)

The expression vector of claim 25, wherein the vector is a plasmid vector.

### Claim 28 (depends on 25)

The expression vector of claim 25, wherein the vector is an integrating vector.

### Claim 29 (depends on 9)

A cell genetically engineered to comprise the nucleic acid of claim 9.