# US 10,441,649 B2 · Targeting moiety peptide epitope complexes having a plurality of T-cell epitopes

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- Number: US 10,441,649 B2
- Document ID: US10441649B2
- Status: Granted
- Kind: B2
- Application number: 15/012,115
- Filed: 2016-02-01
- Published: 2016-08-04
- Granted: 2019-10-15
- Earliest claimed: 2015-02-02
- Assignees: The University of Birmingham
- Applicants: The University of Birmingham
- Inventors: Mark Cobbold; David Millar
- Web page: https://patentgrep.com/patent/US10441649B2

## CPC

- A61K 39/245: Herpetoviridae, e.g. herpes simplex virus
- A61K 47/646: {the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines}
- A61K 47/6811: {the drug being a protein or peptide, e.g. transferrin or bleomycin}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6881: {Cluster-antibody conjugates, i.e. the modifying agent consists of a plurality of antibodies covalently linked to each other or of different antigen-binding fragments covalently linked to each other}
- A61P 31/22: for herpes viruses
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2039/585: {wherein the target is cancer}
- A61K 2039/6056: {Antibodies}
- C12N 2710/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

A variety of targeting moiety peptide epitope complexes (TPECs) are described in different embodiments. In each of the embodiments, however, a targeting moiety may be used to deliver the TPEC to an area of unwanted cells, allowing for a therapeutic effect to be delivered locally. The TPEC also contains a plurality of T-cell epitopes. The TPEC further comprises cleavage sites that release the T-cell epitopes from the targeting agent, and in some embodiments from each other, when they are in the microenvironment of the unwanted cells. Although the arrangement and number of T-cell epitopes varies in different embodiments described herein, once cleaved from the targeting agent (and any neighboring T-cell epitopes), the T-cell epitopes function by stimulating an immune response against the unwanted cells.

## Claims

### Claim 1

A composition for retargeting a virus-specific existing T-cell immune response to cancer cells comprising a targeting moiety peptide epitope complex (TPEC) wherein:
a. T is a targeting moiety that is an antibody or antigen-binding fragment thereof capable of targeting cancer cells;
b. L is at least one linker capable of linkage to T where L is a peptide bond or at least one peptide;
c. C is at least one cleavage site cleaved by an enzyme outside of the cancer cell and expressed by the cancer cell or cleaved by a protease that is outside of the cancer cell and colocalized to the cancer cell by a targeting moiety that is the same or different from the targeting moiety in the TPEC; and
d. E is at least one viral T-cell epitope that elicits an existing immune response in a human subject and binds to a HLA molecule on the surface of the cancer cells of the human subject and has a HLA matched to the subject,
wherein the L, C, and E moieties are arranged in a pattern of at least one of L-(C-E)n, wherein n is an integer of at least 2 and with each C-E attached to the L in series.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the composition comprises a plurality of more than 10 T-cell epitopes conjugated to the targeting moiety with at least one cleavage site.

### Claim 3 (depends on 1)

The composition of claims 1, wherein the plurality of T-cell epitopes are not all identical.

### Claim 4 (depends on 1)

The composition of claim 1, wherein at least one T-cell epitope is an MHC Class I restricted peptide.

### Claim 5 (depends on 1)

The composition of claim 1, wherein at least one T-cell epitope is an MHC Class II restricted peptide.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the plurality of T-cell epitopes are from about 7 to about 14 amino acids in length.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the composition comprises at least about 2, 3, 4, 5, 6, 7, 8, 9, or 10 T cell epitopes.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the T-cell epitopes are chosen from CMV, influenza, EBV, hepatitis, chicken pox, mumps, measles, rubella, polio, rotavirus, vaccinia, and yellow fever T-cell epitopes.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the composition comprises T-cell epitopes from at least two different viruses.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the T-cell epitopes are chosen from HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G, CD1d, and MR1.

### Claim 11 (depends on 1)

The composition of claim 1, wherein the T-cell epitopes are chosen from HLA-A*01, HLA-A*02, HLA-A*03, HLA-A*11, HLA-B*44, HLA-B*07, HLA-B*08, HLA-B*15, HLA-B*35, HLA-B*40, HLA-C*07, HLA-C*03, HLA-C*05, HLA-C*04, HLA-C*06, and HLA-E*0101 restricted antigens.

### Claim 12 (depends on 1)

The composition of claim 1, wherein the composition comprises at least the following T-cell epitopes: HLA-A*02, HLA-A*01, and HLA-A*03.

### Claim 13 (depends on 1)

The composition of claim 1, wherein the T-cell epitopes comprise at least one of SEQ ID NOS: 1-2, 5-7, 15-57.

### Claim 14 (depends on 1)

The composition of claim 1, wherein the T-cell epitopes are flanked on one or both ends by at least one human protein domain.

### Claim 15 (depends on 1)

The composition of claim 1, wherein the enzyme expressed by the cancer cells is a protease.

### Claim 16 (depends on 1)

The composition of claim 1, wherein the antibody or antigen-binding fragment thereof is an anti-CEA or anti-CEACAM antibody or antigen-binding fragment thereof.