# US 11,897,929 B2 · Compositions and methods for targeted cytokine delivery

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- Number: US 11,897,929 B2
- Document ID: US11897929B2
- Status: Granted
- Kind: B2
- Application number: 17/238,995
- Filed: 2021-04-23
- Published: 2021-09-16
- Granted: 2024-02-13
- Earliest claimed: 2016-02-05
- Assignees: Washington University
- Applicants: Washington University
- Inventors: Alexander Sasha Krupnick; Daved Henry Fremont; Eric Reed Lazear; John Westwick
- Web page: https://patentgrep.com/patent/US11897929B2

## CPC

- C07K 14/55: IL-2
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61P 35/00: Antineoplastic agents
- C07K 14/52: Cytokines; Lymphokines; Interferons
- C07K 14/5418: {IL-7}
- C07K 14/5443: {IL-15}
- C07K 14/545: IL-1
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- C07K 16/2851: {against the lectin superfamily, e.g. CD23, CD72}
- 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)
- 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
- 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)
- 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
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present disclosure encompasses compositions and methods for targeted cytokine delivery. The compositions disclosed herein comprise a cytokine linked to an NKG2D ligand or PD1 ligand and may improve immunotherapy by limiting side effects associated with immunotherapy. The present disclosure also encompasses compositions and methods for recruiting cytotoxic lymphocytes to target cells using NKG2D receptor ligands or PD1 ligands. The compositions disclosed herein comprise a NKG2D receptor ligand and a targeting molecule and may improve immunotherapy by limiting side effects associated with immunotherapy.

## Claims

### Claim 1

A method of expanding cytotoxic lymphocytes ex vivo, comprising culturing a population of lymphocytes in the presence of a chimeric peptide,
wherein the chimeric peptide comprises an orthopoxvirus major histocompatibility complex class 1-like protein (OMCP) peptide linked to an interleukin-2 (IL-2) mutant peptide comprising the amino acid sequence of SEQ ID NO: 5 comprising at least one mutation, wherein the at least one mutation is R38A, F42K, or C125S relative to SEQ ID NO: 5 wherein the OMCP peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 13, and SEQ ID NO: 14, and
wherein the population of lymphocytes comprises cytotoxic lymphocytes.

### Claim 2 (depends on 1)

The method of claim 1, wherein the OMCP peptide comprises the amino acid sequence of SEQ ID NO: 7.

### Claim 3 (depends on 1)

The method of claim 1, wherein the OMCP peptide comprises the amino acid sequence of SEQ ID NO: 13.

### Claim 4 (depends on 3)

The method of claim 3, wherein the OMCP peptide comprises the amino acid sequence of SEQ ID NO: 14.

### Claim 5 (depends on 1)

The method of claim 1, wherein the cytotoxic lymphocytes comprise CD8+ T cells and/or NK cells.