# US 11,304,978 B2 · Compositions and methods for the treatment of cancer using a CD8 engineered T cell therapy

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- Number: US 11,304,978 B2
- Document ID: US11304978B2
- Status: Granted
- Kind: B2
- Application number: 17/100,223
- Filed: 2020-11-20
- Published: 2021-03-25
- Granted: 2022-04-19
- Earliest claimed: 2019-05-01
- Assignees: Pact Pharma, Inc.
- Applicants: Pact Pharma, Inc.
- Inventors: Barbara Sennino; Kyle Jacoby; Stefanie Mandl-Cashman; Michael M. Dubreuil; John Gagnon; Alex Franzusoff
- Web page: https://patentgrep.com/patent/US11304978B2

## CPC

- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/30: characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K 40/32: T-cell receptors [TCR]
- A61K 40/42: Cancer antigens
- A61K 40/4201: {Neoantigens}
- C07K 14/70517: {CD8}
- C12N 5/0636: {T lymphocytes}
- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- C12N 9/226: {Class 2 CAS enzyme complex, e.g. single CAS protein}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 15/90: Stable introduction of foreign DNA into chromosome
- C12N 15/907: {in mammalian cells}
- C07K 2319/02: containing a signal sequence
- C07K 2319/50: containing protease site
- C12N 9/0071: {acting on paired donors with incorporation of molecular oxygen (1.14)}
- C12N 2310/20: involving clustered regularly interspaced short palindromic repeats [CRISPR]
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)

## Abstract

Compositions comprising and methods for the treatment of cancer using a neoTCR based cell therapy with a CD8 expression construct.

## Claims

### Claim 1

A composition comprising a peripheral T cell comprising:
a. an exogenous T cell receptor (TCR) recognizing a neoantigen; and
b. an exogenous CD8 comprising:
i. a CD8α signal peptide, a CD8α extracellular domain, a CD8α transmembrane domain, and a CD8β intracellular domain; or
ii. a CD8α signal peptide, a CD8α extracellular domain, a CD8α transmembrane domain, and a CD4 intracellular domain.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the exogenous CD8 comprises:
a. a CD8α signal peptide set forth in SEQ ID NO:139, a CD8α extracellular domain set forth in SEQ ID NO:140, a CD8α transmembrane domain set forth in SEQ ID NO:141, and a CD8β intracellular domain set forth in SEQ ID NO: 147; or
b. a CD8α signal peptide set forth in SEQ ID NO:139, a CD8α extracellular domain set forth in SEQ ID NO:140, a CD8α transmembrane domain set forth in SEQ ID NO:141, and a CD4 intracellular domain set forth in SEQ ID NO: 148.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the exogenous CD8 further comprises at least one of a 2A sequence, a linker, and a protease cleavage site.

### Claim 4 (depends on 3)

The composition of claim 3, wherein the protease cleavage site is a Furin cleavage site.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the exogenous TCR is a patient derived TCR.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the exogenous TCR comprises a signal sequence, a first and second 2A sequence, and a second TCR polypeptide sequence.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the cell is a patient-derived cell.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the peripheral T cell is:
a. CD45RA+, CD62L+, CD28+, CD95−, CCR7+, and CD27+;
b. CD45RA+, CD62L+, CD28+, CD95+, CD27+, CCR7+; or
c. CD45RO+, CD62L+, CD28+, CD95+, CCR7+, CD27+, CD127+.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the exogenous CD8 is encoded by a CD8 Construct 3 or a CD8 Construct 4.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the composition further comprises a pharmaceutically acceptable excipient.

### Claim 11 (depends on 1)

The composition of claim 1, further comprising a cryopreservation agent, serum album, and a crystalloid solution.

### Claim 12

A composition comprising a peripheral T cell comprising:
a. an exogenous T cell receptor (TCR) recognizes a neoantigen; and
b. an exogenous CD8 comprising:
i. a CD8α signal peptide, a CD8α extracellular domain, a CD8α transmembrane domain, and a CD8β intracellular domain; or
ii. a CD8α signal peptide, a CD8α extracellular domain, a CD8α transmembrane domain, and a CD4 intracellular domain;
wherein the exogenous TCR is encoded by a polynucleotide integrated into a TRAC and/or TRBC locus of the cell.

### Claim 13 (depends on 12)

The composition of claim 12, wherein the exogenous CD8 comprises:
a. a CD8α signal peptide set forth in SEQ ID NO:139, a CD8α extracellular domain set forth in SEQ ID NO:140, a CD8α transmembrane domain set forth in SEQ ID NO:141, and a CD8β intracellular domain set forth in SEQ ID NO: 147; or
b. a CD8α signal peptide set forth in SEQ ID NO:139, a CD8α extracellular domain set forth in SEQ ID NO:140, a CD8α transmembrane domain set forth in SEQ ID NO:141, and a CD4 intracellular domain set forth in SEQ ID NO: 148.

### Claim 14 (depends on 12)

The composition of claim 12, wherein the exogenous CD8 is encoded by a polynucleotide integrated into the TRAC and/or TRBC locus of the cell.

### Claim 15 (depends on 12)

The composition of claim 12, wherein the exogenous CD8 further comprises at least one of a 2A sequence, a linker, and a protease cleavage site.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the protease cleavage site is a Furin cleavage site.

### Claim 17 (depends on 12)

The composition of claim 12, wherein the exogenous TCR is a patient derived TCR.

### Claim 18 (depends on 12)

The composition of claim 12, wherein the exogenous TCR comprises a signal sequence, a first and second 2A sequence, and a second TCR polypeptide sequence.

### Claim 19 (depends on 12)

The composition of claim 12, wherein the cell is a patient-derived cell.

### Claim 20 (depends on 12)

The composition of claim 12, wherein the peripheral T cell is:
a. CD45RA+, CD62L+, CD28+, CD95−, CCR7+, and CD27+;
b. CD45RA+, CD62L+, CD28+, CD95+, CD27+, CCR7+; or
c. CD45RO+, CD62L+, CD28+, CD95+, CCR7+, CD27+, CD127+.

### Claim 21 (depends on 12)

The composition of claim 12, wherein the exogenous CD8 is encoded by a CD8 Construct 3 or a CD8 Construct 4.

### Claim 22 (depends on 12)

The composition of claim 12, wherein the composition further comprises a pharmaceutically acceptable excipient.

### Claim 23 (depends on 12)

The composition of claim 12, further comprising a cryopreservation agent, serum album, and a crystalloid solution.

### Claim 24 (depends on 12)

The composition of claim 12, wherein the polynucleotide is non-virally integrated into the TRAC or TRBC locus.