# US 2023/0265149 A1 · Encapsulated cells expressing il-2 and uses thereof

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- Number: US 2023/0265149 A1
- Document ID: US20230265149A1
- Status: Published application
- Kind: A1
- Application number: 18/047,856
- Filed: 2022-10-19
- Published: 2023-08-24
- Earliest claimed: 2021-10-20
- Assignees: William Marsh Rice University
- Applicants: William Marsh Rice University
- Inventors: Omid VEISEH; David ZHANG; Sudip MUKHERJEE; Maria RUOCCO; Michael DOERFERT; Amanda NASH; Samira AGHLARA-FOTOVAT
- Web page: https://patentgrep.com/patent/US20230265149A1

## CPC

- C07K 14/55: IL-2
- A61P 35/00: Antineoplastic agents
- C12N 5/0012: {Cell encapsulation}
- C12N 5/0621: {Eye cells, e.g. cornea, iris pigmented cells (photoreceptors C12N5/062)}
- C12N 2501/2302: Interleukin-2 (IL-2)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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 disclosure relates to implantable constructs (encapsulated cells) designed to deliver antigenic therapeutic reagents, such as IL-2.

## Claims

### Claim at position 1

1-68. (canceled)

### Claim 69

A population of encapsulated cells comprising an oligonucleotide molecule encoding native human IL-2.

### Claim 70 (depends on 69)

The population of encapsulated cells of claim 69, wherein the oligonucleotide encoding native human IL-2 comprises a sequence of SEQ ID NO: 1 or codon optimized oligonucleotide sequence thereof.

### Claim 71 (depends on 70)

The population of encapsulated cells of claim 70, wherein the codon-optimized oligonucleotide encoding native human IL-2 comprises a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3.

### Claim 72 (depends on 69)

The population of encapsulated cells of claim 69, wherein the cell produces recombinant native human IL-2 protein.

### Claim 73 (depends on 72)

The population of encapsulated cells of claim 72, wherein the recombinant native human IL-2 protein expressed by the cells comprises the amino acid sequence of SEQ ID NO: 2.

### Claim 74 (depends on 69)

The population of encapsulated cells of claim 69, wherein the population of cell produces about 1 to about 10, about 1 to about 5, or about 2 to about 4 PCD (picograms/cell/day) of recombinant native human IL-2.

### Claim 75 (depends on 69)

The population of encapsulated cells of claim 69, wherein the cells are retinal pigment epithelial cells.

### Claim 76 (depends on 69)

The population of encapsulated cells of claim 69, wherein the cells are encapsulated with a polymeric hydrogel.

### Claim 77 (depends on 76)

The population of encapsulated cells of claim 76, wherein the polymeric hydrogel comprises chitosan, cellulose, hyaluronic acid, or alginate.

### Claim 78 (depends on 77)

The population of encapsulated cells of claim 77, wherein the alginate comprises SLG20.

### Claim 79 (depends on 69)

The population of encapsulated cells claim 69, wherein the encapsulated cells remain viable for at least 15, 20, 25, or 28 days.

### Claim 80 (depends on 69)

The population of encapsulated cells of claim 69, wherein the encapsulated cells do not proliferate.

### Claim 81 (depends on 69)

A pharmaceutical composition comprising the population of encapsulated cells of claim 69.

### Claim 82 (depends on 69)

A method of treating a tumor in a subject, the method comprising implanting in the intraperitoneal space of the subject a pharmaceutical composition comprising a plurality of encapsulated cells of claim 69 to the subject to treat the cancer.

### Claim 83 (depends on 82)

The method of claim 82, wherein the concentration of recombinant native human IL-2 in the intraperitoneal space at day 5 post implantation is at least 5000 pg/ml, 10000 pg/ml, 15000 pg/ml, 20000 pg/ml, 50000 pg/ml, 100000 pg/ml, or 150000 pg/ml.

### Claim 84 (depends on 82)

The method of claim 82, wherein the concentration of the recombinant native human IL-2 in the intraperitoneal space is at least 100× greater than the concentration of the recombinant native human IL-2 in the blood of the subject.

### Claim 85 (depends on 82)

The method of claim 82, wherein the concentration of the recombinant native human IL-2 in the blood of the subject is substantially undetectable 5 days after implantation.

### Claim 86 (depends on 82)

The method of claim 82, wherein the recombinant native IL-2 protein is detectable in the intraperitoneal space of the subject at least 1, 4, 7, 14, 21, or 30 days post implantation.

### Claim 87 (depends on 69)

A method of:
treating a tumor in a subject by generating memory immunity, the method comprising implanting in the subject a pharmaceutical composition comprising the population of encapsulated cells of claim 69;
selectively activating CD8 positive effector T cells in a subject, the method comprising implanting in the subject a pharmaceutical composition comprising a population of encapsulated cells of claim 69;
providing systemic treatment to a subject with cancer, the method comprising implanting in the intraperitoneal space of the subject a pharmaceutical composition comprising a plurality of encapsulated cells of claim 69, whereby the pharmaceutical composition stimulates the activation of immune cells in the intraperitoneal space and the activated immune cells migrate to a region of the subject that is distal to the intraperitoneal space to treat the cancer systemically in the subject; or
providing systemic treatment to a subject with cancer, the method comprising implanting in the intraperitoneal space of the subject a pharmaceutical composition comprising a plurality of encapsulated cells of claim 69, whereby the pharmaceutical composition activates immune cells and the activated immune cells migrate out of the intraperitoneal space to treat the cancer in the subject.

### Claim 88

A method of preparing encapsulated cells producing a recombinant protein, the method comprising:
feeding through a coaxial needle a first composition comprising a polymeric hydrogel and a second composition comprising cells to be encapsulated suspended in a polymeric hydrogel to drop into a crosslinking solution to form the encapsulated cells, wherein the crosslinking solution comprises a sugar alcohol, a buffer, a metal salt, and a surfactant.