# US 12,006,345 B2 · Untargeted and targeted IL-10 Fc-fusion proteins

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- Number: US 12,006,345 B2
- Document ID: US12006345B2
- Status: Granted
- Kind: B2
- Application number: 16/798,247
- Filed: 2020-02-21
- Published: 2021-06-10
- Granted: 2024-06-11
- Earliest claimed: 2019-02-21
- Assignees: Xencor, Inc.
- Applicants: Xencor, Inc
- Inventors: Gregory Moore; Rajat Varma; Yoon Kyung Kim; Rumana Rashid; Alex Nisthal; Juan Diaz; Matthew Bernett; Michael Hedvat
- Web page: https://patentgrep.com/patent/US12006345B2

## CPC

- C07K 14/5428: {IL-10}
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- 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)

## Abstract

The present invention provides untargeted and targeted IL-10-Fc fusion proteins, compositions and methods of use thereof. The targeted IL-10-Fc fusion proteins includes those that bind PD-1, TIGIT, CD8 and NKG2D.

## Claims

### Claim 1

A composition comprising a variant interleukin-10 (IL-10) monomer domain consisting of a parent IL-10 monomer domain with an amino acid substitution or a set of amino acid substitutions,
wherein the parent IL-10 monomer domain is SEQ ID NO:3 or SEQ ID NO:4;
wherein the amino acid substitution or the set of amino acid substitutions are selected from the group consisting of: N21D, D28N, Q38E, Q42E, D44N, N45D, E142Q, D144N, E151Q, Q38E/D41N, Q38E/Q42E, Q38E/N45D, Q38E/E142Q, Q38E/D144N, D41N/Q42E, D41N/N45D, D41N/E142Q, D41N/D144N, Q42E/N45D, Q42E/E142Q, Q42E/D144N, N45D/E142Q, N45D/D144N, E142Q/D144N, N21D/Q42E, N21D/N45D, N21D/E151Q, N21D/N45E, Q42E/E151Q, N45D/E151Q, N21D/Q42E/N45D, N21D/Q42E/E151Q, Q42E/N45D/E151Q, N21D/Q42E/N45E, and N21D/Q42E/N45D/E151Q of SEQ ID NO:3 or SEQ ID NO:4.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the variant IL-10 monomer domain comprises a set of amino acid substitutions selected from the group consisting of Q38E/D41N, Q38E/Q42E, Q38E/N45D, Q38E/E142Q, Q38E/D144N, D41N/Q42E, D41N/N45D, D41N/E142Q, D41N/D144N, Q42E/N45D, Q42E/E142Q, Q42E/D144N, N45D/E142Q, N45D/D144N, E142Q/D144N, N21D/Q42E, N21D/N45D, N21D/E151Q, N21D/N45E, Q42E/E151Q, N45D/E151Q, N21D/Q42E/N45D, N21D/Q42E/E151Q, Q42E/N45D/E151Q, N21D/Q42E/N45E, and N21D/Q42E/N45D/E151Q.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the amino acid substitution or set of amino acid substitutions is selected from the group consisting of N45D, N45D/D144N, and Q38E/N45D of SEQ ID NO:3 or SEQ ID NO:4.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the variant IL-10 monomer domain comprises the amino acid sequence of SEQ ID NO:562.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the variant IL-10 monomer domain comprises the amino acid sequence of SEQ ID NO:568.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the variant IL-10 monomer domain comprises the amino acid sequence of SEQ ID NO:571.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the variant IL-10 monomer domain comprises the amino acid sequence of SEQ ID NO:132.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the variant IL-10 monomer domain comprises the amino acid sequence of SEQ ID NO:139.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the variant IL-10 monomer domain comprises the amino acid sequence of SEQ ID NO:150.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the variant IL-10 monomer domain comprises the amino acid sequence of SEQ ID NO:171.

### Claim 11 (depends on 1)

The composition of claim 1, wherein the variant IL-10 monomer domain comprises the amino acid sequence of SEQ ID NO:178.

### Claim 12 (depends on 1)

The composition of claim 1, wherein the variant IL-10 monomer domain comprises the amino acid sequence of SEQ ID NO:189.

### Claim 13 (depends on 1)

The composition of claim 1, wherein the amino acid substitution or set of amino acid substitutions are selected from the group consisting of N21D, Q38E, Q42E, N45D, E142Q, E151Q, Q38E/D41N, Q38E/Q42E, Q38E/N45D, Q38E/E142Q, Q38E/D144N, D41N/Q42E, D41N/N45D, D41N/E142Q, D41N/D144N, Q42E/N45D, Q42E/E142Q, Q42E/D144N, N45D/E142Q, N45D/D144N, E142Q/D144N, N21D/Q42E, N21D/N45D, N21D/E151Q, N21D/N45E, Q42E/E151Q, N45D/E151Q, N21D/Q42E/N45D, N21D/Q42E/E151Q, Q42E/N45D/E151Q, N21D/Q42E/N45E, and N21D/Q42E/N45D/E151Q of SEQ ID NO:3 or SEQ ID NO:4.