# US 11,439,664 B2 · Biologically relevant orthogonal cytokine/receptor pairs

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- Number: US 11,439,664 B2
- Document ID: US11439664B2
- Status: Granted
- Kind: B2
- Application number: 16/289,274
- Filed: 2019-02-28
- Published: 2019-06-20
- Granted: 2022-09-13
- 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; David Baker; Chris King
- Web page: https://patentgrep.com/patent/US11439664B2

## 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 a variant human CD122 polypeptide, the variant human CD122 polypeptide comprising amino acid substitutions at positions H133 and Y134, wherein numbering is made in reference to SEQ ID NO: 1.

### Claim 2 (depends on 1)

An expression vector comprising the nucleic acid of claim 1.

### Claim 3 (depends on 2)

A cell genetically engineered to comprise the vector of claim 2.

### Claim 4 (depends on 1)

The nucleic acid of claim 1 wherein the variant human CD122 polypeptide further comprises an amino acid substitution or deletion at one or more residues selected from R41, R42, Q70, K71, T73, T74, V75, S132, F135, E136, and Q214.

### Claim 5 (depends on 4)

The nucleic acid of claim 4 wherein the variant human CD122 polypeptide further comprises an amino acid substitution or deletion at one or more residues selected from Q70, and T73.

### Claim 6 (depends on 4)

The nucleic acid of claim 4 wherein the variant human CD122 polypeptide further comprises an amino acid substitution at one or more residues selected from Q70, and T73.

### Claim 7 (depends on 6)

The nucleic acid of claim 6 wherein the variant human CD122 polypeptide comprises one or more amino acid substitutions selected from 070Y, T73 D, T73Y, H133D, H133E, H133K, Y134F, Y134E, and Y134R.

### Claim 8 (depends on 1)

The nucleic acid of claim 1 wherein the variant human CD122 polypeptide comprises amino acid substitutions at position 133 selected from H133D, H133E, and H133K, and at position 134 selected from Y134F, Y134E, and Y134R.

### Claim 9 (depends on 8)

The nucleic acid of claim 8 wherein the variant human CD122 polypeptide comprises amino acid substitutions H133D and Y134F.

### Claim 10 (depends on 1)

The nucleic acid of claim 1 further comprising a nucleic acid encoding a signal sequence, the nucleic acid encoding the signal sequence operably linked to the nucleic acid encoding the variant human CD122 polypeptide.

### Claim 11 (depends on 10)

The nucleic acid of claim 10 wherein the signal sequence is the naturally occurring human CD122 signal sequence.

### Claim 12 (depends on 11)

The nucleic acid of claim 11 wherein the variant human CD122 polypeptide comprises amino acid substitutions at position 133 selected from H1 33D, H1 33E, and H133K, and at position 134 selected from Y134F, Y134E, and Y134R.

### Claim 13 (depends on 12)

The nucleic acid of claim 12 wherein the variant human CD122 polypeptide comprises the amino acid substitutions H133D and Y134F.

### Claim 14 (depends on 2)

The expression vector of claim 2 wherein the expression vector is a plasmid or viral vector.

### Claim 15 (depends on 14)

The expression vector of claim 14 wherein the expression vector is a viral vector.

### Claim 16 (depends on 15)

The expression vector of claim 15, wherein the expression vector is a retroviral vector or lentiviral vector.

### Claim 17 (depends on 14)

The expression vector of claim 14, wherein the variant human CD122 polypeptide further comprises an amino acid substitution or deletion at one or more residues selected from R41, R42, Q70, K71, T73, T74, V75, S132, F135, E136, and Q214.

### Claim 18 (depends on 14)

The expression vector of claim 14 wherein the variant human CD122 polypeptide comprises an amino acid substitution or deletion at one or more residues selected from Q70, T73, H133 and Y134.

### Claim 19 (depends on 18)

The expression vector of claim 18 wherein the variant human CD122 polypeptide further comprises one or more amino acid substitutions selected from Q70Y, T73D, and T73Y.

### Claim 20 (depends on 19)

The expression vector of claim 19 wherein the variant human CD122 polypeptide comprises amino acid substitutions at position 133 selected from H133D, H133E, and H133K, and at position 134 selected from Y134F, Y134E, and Y134R.

### Claim 21 (depends on 20)

The expression vector of claim 20 wherein the vector is a lentiviral vector or a retroviral vector.

### Claim 22 (depends on 20)

The expression vector of claim 20 wherein the variant human CD122 polypeptide comprises amino acid substitutions H133D and Y134F.

### Claim 23 (depends on 14)

The expression vector of claim 14 further comprising a nucleic acid encoding a signal sequence operably linked to the nucleic acid encoding the variant human CD122 polypeptide.

### Claim 24 (depends on 23)

The expression vector of claim 23 wherein the signal sequence is the naturally occurring human CD122 signal sequence.

### Claim 25 (depends on 23)

The expression vector of claim 23 wherein the variant human CD122 polypeptide comprises amino acid substitutions at position 133 selected from H133D, H133E, and H133K, and at position 134 selected from Y134F, Y134E, and Y134R.

### Claim 26 (depends on 23)

The expression vector of claim 23 wherein the variant human CD122 polypeptide comprises the amino acid substitutions H133D and Y134F.

### Claim 27 (depends on 26)

The expression vector of claim 26 wherein the vector is a viral vector.

### Claim 28 (depends on 26)

The expression vector of claim 26 wherein the vector is lentiviral vector or retroviral vector.

### Claim 29 (depends on 28)

The expression vector of claim 28 wherein the vector is a lentiviral vector.

### Claim 30 (depends on 25)

The expression vector of claim 25 wherein the vector further comprises a nucleic acid encoding a second heterologous polypeptide.

### Claim 31 (depends on 30)

The expression vector of claim 30 wherein first and second polypeptide are operably linked to a single promoter.

### Claim 32 (depends on 3)

The genetically engineered cell of claim 3, wherein the cell is a mammalian cell.

### Claim 33 (depends on 32)

The genetically engineered cell of claim 32, wherein the cell is an immune cell.

### Claim 34 (depends on 33)

The genetically engineered cell of claim 33, wherein the immune cell is a T cell.

### Claim 35 (depends on 34)

The genetically engineered cell of claim 34, wherein the T cell is selected from CD8+ T cells, CD4+ T cells, helper T cells, regulatory T cells, memory T cells, NKT cells, γδT cells.

### Claim 36 (depends on 33)

The genetically engineered cell of claim 33 wherein the expression vector is a viral vector comprising a nucleic acid encoding a variant human CD122 polypeptide wherein the variant human CD122 polypeptide comprises an amino acid substitution or deletion at one or more residues selected from R41, R42, Q70, K71, T73, T74, V75, S132, F135, E136, and Q214.

### Claim 37 (depends on 36)

The genetically engineered cell of claim 36 wherein the variant human CD122 polypeptide comprises an amino acid substitution or deletion at one or more residues selected from Q70 and T73.

### Claim 38 (depends on 37)

The genetically engineered cell of claim 37 wherein the variant human CD122 polypeptide comprises one or more amino acid substitutions selected from Q70Y, T73D, T73Y, amino acid substitutions at position 133 selected from H133D, H133E, and H133K, and at position 134 selected from Y1 34F, Y1 34E, and Y1 34R.

### Claim 39 (depends on 34)

The genetically engineered cell of claim 34 wherein the variant human CD122 polypeptide comprises an amino acid substitution or deletion at one or more residues selected from H133 and Y134.

### Claim 40 (depends on 39)

The genetically engineered cell of claim 39 wherein the variant human CD122 polypeptide comprises amino acid substitutions at position 133 selected from H133D, H133E, and H133K, and at position 134 selected from Y134F, Y134E, and Y134R.

### Claim 41 (depends on 39)

The genetically engineered cell of claim 39 wherein the variant human CD122 polypeptide comprises amino acid substitutions at positions H133 and Y134.

### Claim 42 (depends on 41)

The genetically engineered cell of claim 41 wherein the variant human CD122 polypeptide comprises one or more amino acid substitutions selected from selected from H133D and Y134F.

### Claim 43 (depends on 41)

The genetically engineered cell of claim 41 further comprising a nucleic acid encoding a signal sequence operably linked to the nucleic acid encoding the variant human CD122 polypeptide.

### Claim 44 (depends on 43)

The genetically engineered cell of claim 43 wherein the signal sequence is the naturally occurring human CD122 signal sequence.

### Claim 45 (depends on 41)

The genetically engineered cell of claim 41 wherein the vector is a lentiviral vector or a retroviral vector.

### Claim 46 (depends on 45)

The genetically engineered cell of claim 45 wherein the vector is a lentiviral vector.

### Claim 47 (depends on 46)

The genetically engineered cell of claim 46 further comprising a nucleic acid encoding a signal sequence operably linked to the nucleic acid encoding the variant human CD122 polypeptide.

### Claim 48 (depends on 47)

The genetically engineered cell of claim 47 wherein the signal sequence is the naturally occurring human CD122 signal sequence.

### Claim 49 (depends on 48)

The genetically engineered cell of claim 48 wherein the vector is a lentiviral vector or a retroviral vector.

### Claim 50 (depends on 49)

The genetically engineered cell of claim 49 wherein the vector is a lentiviral vector.

### Claim 51 (depends on 50)

The genetically engineered cell of claim 50 wherein the vector further comprises a nucleic acid encoding a second heterologous polypeptide.

### Claim 52 (depends on 51)

The genetically engineered cell of claim 51 wherein first and second polypeptide are operably linked to a single promoter.