# US 11,110,150 B2 · Complexes of IL-15 and IL-15Ralpha and uses thereof

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- Number: US 11,110,150 B2
- Document ID: US11110150B2
- Status: Granted
- Kind: B2
- Application number: 16/291,561
- Filed: 2019-03-04
- Published: 2019-09-26
- Granted: 2021-09-07
- Earliest claimed: 2007-06-27
- Assignees: Novartis AG; The United States of America, as represented by the Secretary, Department of Health and Human Services
- Applicants: Novartis AG; The United States of America, as Represented by the Secretary, Department of Health and Human Services
- Inventors: Barbara K. Felber; Sergio Finkielsztein; George N. Pavlakis; John V. Vournakis
- Web page: https://patentgrep.com/patent/US11110150B2

## CPC

- A61K 38/2086: {IL-13 to IL-16}
- A61K 35/13: Tumour cells, irrespective of tissue of origin (tumour vaccines A61K39/00)
- A61K 38/1793: {for cytokines; for lymphokines; for interferons}
- A61K 39/0011: {Cancer antigens}
- A61K 39/00114: {Interleukins [IL]}
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- 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
- C07K 16/244: {Interleukins [IL]}
- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- C12N 5/0686: {Kidney cells}
- C12N 5/0693: {Tumour cells; Cancer cells}
- C12N 15/85: for animal cells
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 2039/5152: {Tumor cells}
- A61K 2039/5156: {expressing foreign proteins}
- A61K 2039/55527: {Interleukins}
- C07K 14/5443: {IL-15}
- C07K 14/7155: {for interleukins [IL]}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/00: Fusion polypeptide
- C12N 2500/90: Serum-free medium, which may still contain naturally-sourced components
- C12N 2501/2315: Interleukin-15 (IL-15)
- C12N 2510/00: Genetically modified cells
- 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)

## Abstract

The present invention relates to agents that modulate interleukin-15 (“IL-15”) signal transduction or function (“Therapeutic Agents”) and the use ol” those agents to modulate immune function. The Therapeutic Agents target the interaction between IL-15 and its receptor and modulate IL-15-induced signal transduction. The Therapeutic Agents may be formulated with polymers, such as poly-β-1-♦4-N-acetylglucosamine. for administration to a human subject to modulate IL-15-mediated immune function.

## Claims

### Claim 1

A method of recombinantly producing a human IL-15 and a human IL-15Ra complex, comprising:
(a) culturing a cell expressing a human IL-15 encoded by a nucleic acid sequence with at least 95% identity to nucleic acid residues 1 to 489 of SEQ ID NO:2; and a human IL15Ra encoded by: (i) a nucleic acid sequence with at least 95% identity to nucleic acid residues 1 to 804 of SEQ ID NO:5; or (ii) a nucleic acid sequence with at least 95% identity to nucleic acid residues 1 to 615 of SEQ ID NO:6 and
(b) purifying the human IL-15 and human IL-15Ra complex,
wherein the cell expresses at least 150 ng/million cells of human IL-15 per day when cultured in serum-free media.

### Claim 2 (depends on 1)

The method of claim 1, wherein the human IL-15 is encoded by the nucleic acid sequence comprising nucleic acid residues 1 to 489 of SEQ ID NO:2; and the human IL15Ra is encoded by the nucleic acid sequence comprising nucleic acid residues 1 to 804 of SEQ ID NO:5.

### Claim 3 (depends on 1)

The method of claim 1, wherein the human IL-15 is encoded by the nucleic acid sequence comprising nucleic acid residues 1 to 489 of SEQ ID NO:2; and the human IL15Ra is encoded by the nucleic acid sequence comprising nucleic acid residues 1 to 615 of SEQ ID NO:6.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cell is selected from the group consisting of: 293, COS, CHO, HeLa, NIH3T3, HepG2, MCF7, RD, PC12, K562, skBr3, BT274, A204, MO7Sb, TFB I, Raji, Jurkat, MOLT-4, CTLL-2, MC-IXC, SK-N-MC, SK-N-DZ, SH-SYSSY, C I27 and BE(2)-C cell line.