# US 11,878,062 B2 · Multimeric T-cell modulatory polypeptides and methods of use thereof

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- Number: US 11,878,062 B2
- Document ID: US11878062B2
- Status: Granted
- Kind: B2
- Application number: 18/334,911
- Filed: 2023-06-14
- Published: 2023-12-07
- Granted: 2024-01-23
- Earliest claimed: 2020-05-12
- Assignees: Cue Biopharma, Inc.
- Applicants: Cue Biopharma, Inc.
- Inventors: Saso Cemerski; Ronald D. Seidel, III; Rodolfo J. Chaparro; John F. Ross
- Web page: https://patentgrep.com/patent/US11878062B2

## CPC

- A61K 47/646: {the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines}
- C07K 14/70539: {MHC-molecules, e.g. HLA-molecules}
- A61K 39/001114: {CD74, Ii, MHC class II invariant chain or MHC class II gamma chain}
- A61K 39/001153: {Wilms tumor 1 [WT1]}
- A61K 47/642: {the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate}
- A61K 47/6425: {the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell}
- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- C07K 14/55: IL-2
- A61K 2039/605: {MHC molecules or ligands thereof}
- A61K 2039/6056: {Antibodies}
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/40: containing a tag for immunodetection, or an epitope for immunisation
- C07K 2319/74: containing a fusion for binding to a cell surface receptor
- 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)
- 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 disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

## Claims

### Claim 1

A homodimer comprising two heterodimers, wherein each heterodimer comprises:
a) a first polypeptide having the amino acid sequence set forth in SEQ ID NO: 423 comprising:
i) a Wilms tumor-1 (WT1) peptide;
ii) a β2-microglobulin (β2M) polypeptide; and
iii) a peptide linker between the WT1 peptide and the β2M polypeptide, wherein the peptide linker comprises a Cys residue, and
b) a second polypeptide having the amino acid sequence set forth in SEQ ID NO: 486 comprising:
i) two variant IL-2 polypeptides;
ii) a major histocompatibility complex (MHC) class I heavy chain polypeptide; and
ii) an immunoglobulin (Ig) Fc polypeptide,
wherein each heterodimer comprises a first disulfide bond formed between (i) the Cys residue in the peptide linker between the WT1 peptide and the β2M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide,
wherein each heterodimer comprises a second disulfide bond formed between a Cys residue in the β2M polypeptide and a Cys residue in the MHC class I heavy chain polypeptide,
wherein two disulfide bonds link the Ig Fc polypeptide of one heterodimer to the Ig Fc polypeptide of the other heterodimer.

### Claim 2 (depends on 1)

A pharmaceutical composition comprising the homodimer of claim 1.

### Claim 3

A homodimer consisting of two heterodimers, wherein each heterodimer comprises:
a) a first polypeptide having the amino acid sequence set forth in SEQ ID NO: 423 comprising:
i) a Wilms tumor-1 (WT1) peptide;
ii) a β2-microglobulin (β2M) polypeptide; and
iii) a peptide linker between the WT1 peptide and the β2M polypeptide, wherein the peptide linker comprises a Cys residue, and
b) a second polypeptide having the amino acid sequence set forth in SEQ ID NO: 486 comprising:
i) two variant IL-2 polypeptides;
ii) a major histocompatibility complex (MHC) class I heavy chain polypeptide; and
ii) an immunoglobulin (Ig) Fc polypeptide,
wherein each heterodimer comprises a first disulfide bond formed between (i) the Cys residue in the peptide linker between the WT1 peptide and the β2M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide,
wherein each heterodimer comprises a second disulfide bond formed between a Cys residue in the β2M polypeptide and a Cys residue in the MHC class I heavy chain polypeptide, and
wherein two disulfide bonds link the Ig Fc polypeptide of one heterodimer to the Ig Fc polypeptide of the other heterodimer.

### Claim 4 (depends on 3)

A pharmaceutical composition comprising the homodimer of claim 3.