# US 2023/0055445 A1 · Pd-1 targeted il-15/il-15ralpha fc fusion proteins and uses in combination therapies thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2023/0055445 A1
- Document ID: US20230055445A1
- Status: Published application
- Kind: A1
- Application number: 17/831,197
- Filed: 2022-06-02
- Published: 2023-02-23
- Earliest claimed: 2018-10-12
- Assignees: Xencor, Inc.
- Applicants: Xencor, Inc.
- Inventors: Matthew Bernett; John R. Desjarlais; Michael Hedvat; Suzanne Schubbert; Christine Bonzon; Rumana Rashid; Rajat Varma
- Web page: https://patentgrep.com/patent/US20230055445A1

## CPC

- C07K 14/5443: {IL-15}
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61P 35/00: Antineoplastic agents
- C07K 16/2818: {against CD28 or CD152}
- C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- 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)
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/524: CH2 domain
- C07K 2317/526: CH3 domain
- C07K 2317/53: Hinge
- C07K 2317/74: Inducing cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/32: fusions with soluble part of a cell surface receptor, "decoy receptors"
- 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
- 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 is directed to novel PD-1 targeted heterodimeric Fc fusion proteins comprising an IL-15/IL-15Rα Fc-fusion protein and a PD-1 antibody fragment-Fc fusion protein. In some embodiments, the PD-1 targeted IL-15/Rα-Fc fusion proteins are administered to a patient to treat cancer. In some embodiments, the PD-1 targeted IL-15/Rα-Fc fusion proteins are administered in combination with a PD-1 blockade antibody such as nivolumab and/or pembrolizumab. In some embodiments, the PD-1 targeted IL-15/Rα-Fc fusion proteins do not compete with a PD-1 blockade antibody such as nivolumab and/or pembrolizumab for antigen binding.

## Claims

### Claim 1

An anti-PD-1 binding domain, said anti-PD-1 binding domain comprising a variable heavy chain domain (“VH domain”) and a variable light chain domain (“VL domain”), wherein said VH domain has at least 95% amino acid sequence identity with SEQ ID NO:5 and said VL domain has at least 95% amino acid sequence identity with SEQ ID NO:6.

### Claim 2 (depends on 1)

The anti-PD-1 binding domain of claim 1, wherein said VH domain has at least 96% amino acid sequence identity with SEQ ID NO:5 and said VL domain has at least 96% amino acid sequence identity with SEQ ID NO:6.

### Claim 3 (depends on 1)

The anti-PD-1 binding domain of claim 1, wherein said VH domain has at least 97% amino acid sequence identity with SEQ ID NO:5 and said VL domain has at least 97% amino acid sequence identity with SEQ ID NO:6.

### Claim 4 (depends on 1)

The anti-PD-1 binding domain of claim 1, wherein said VH domain has at least 98% amino acid sequence identity with SEQ ID NO:5 and said VL domain has at least 98% amino acid sequence identity with SEQ ID NO:6.

### Claim 5 (depends on 1)

The anti-PD-1 binding domain of claim 1, wherein said VH domain has at least 99% amino acid sequence identity with SEQ ID NO:5 and said VL domain has at least 99% amino acid sequence identity with SEQ ID NO:6.

### Claim 6 (depends on 1)

The anti-PD-1 binding domain of claim 1, wherein said VH domain comprises a F32 amino acid substitution; and said VL domain comprises one or more amino acid substitutions selected from the group consisting of: N27dH, K30Y, and S93T, wherein the numbering is according to Kabat.

### Claim 7 (depends on 6)

The anti-PD-1 binding domain of claim 6, wherein said VL domain comprises the amino acid substitutions N27dH, K30Y, and S93T.

### Claim 8 (depends on 1)

The anti-PD-1 binding domain of claim 1, wherein said VH domain is SEQ ID NO:5 and said VL domain is SEQ ID NO:6.

### Claim 9 (depends on 1)

The anti-PD-1 binding domain of claim 1, wherein said VH domain is SEQ ID NO:5 and said VL domain is SEQ ID NO:368.

### Claim 10 (depends on 1)

The anti-PD-1 binding domain of claim 1, wherein said anti-PD-1 binding domain is an scFv further comprising a scFv linker that covalently attaches said VH domain and VL domain to form said scFv domain.

### Claim 11 (depends on 10)

The anti-PD-1 binding domain of claim 10, wherein said scFv linker is (GGGGS)n (SEQ ID NO:10), where n is an integer between 1 and 7.

### Claim 12 (depends on 10)

The anti-PD-1 binding domain of claim 10, wherein said scFv linker is (GKPGS)n (SEQ ID NO:28), where n is an integer between 1 and 6.

### Claim 13 (depends on 1)

A nucleic acid encoding the anti-PD-1 binding domain of claim 1.

### Claim 14 (depends on 1)

A nucleic acid composition comprising:
a) a first nucleic acid encoding the VH domain of claim 1; and
b) a second nucleic acid encoding the VL domain of claim 1.

### Claim 15 (depends on 13)

An expression vector comprising said nucleic acid of claim 13.

### Claim 16 (depends on 14)

An expression vector composition comprising:
a) a first expression vector comprising said first nucleic acid of claim 14; and
b) a second expression vector comprising said second nucleic acid of claim 14.

### Claim 17 (depends on 15, 16)

A host cell comprising said expression vector of claim 15 or said expression vector composition of claim 16.

### Claim 18 (depends on 1, 17)

A method of producing said anti-PD-1 binding domain of claim 1, the method comprising: culturing the host cell of claim 17 under conditions where said anti-PD-1 binding domain is expressed; and recovering said anti-PD-1 binding domain.