# US 12,006,356 B2 · Anti-CCT5 binding molecules and chimeric antigen receptors comprising the same

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

- Number: US 12,006,356 B2
- Document ID: US12006356B2
- Status: Granted
- Kind: B2
- Application number: 16/771,954
- Filed: 2018-12-14
- Published: 2021-03-11
- Granted: 2024-06-11
- Earliest claimed: 2017-12-15
- Assignees: Juno Therapeutics, Inc.
- Applicants: Juno Therapeutics, Inc.
- Inventors: Susan Byrne; Richard Sullivan; Francois Vigneault
- Web page: https://patentgrep.com/patent/US12006356B2

## CPC

- C07K 16/18: against material from animals or humans
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/4204: {Epidermal growth factor receptors [EGFR]}
- A61K 40/4262: {Heat shock proteins}
- A61K 47/6843: {the antibody targeting a material from animals or humans}
- A61P 35/00: Antineoplastic agents
- C07K 14/70521: {CD28, CD152}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C07K 16/2806: {against CD2}
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/30: from tumour cells
- C12N 5/0636: {T lymphocytes}
- A61K 2039/572: {cytotoxic response}
- A61K 2039/804: {Blood cells [leukemia, lymphoma]}
- A61K 2039/812: {Breast}
- A61K 2039/852: {Pancreas}
- A61K 2039/86: {Lung}
- A61K 2039/876: {Skin, melanoma}
- A61K 2039/892: {Reproductive system [uterus, ovaries, cervix, testes]}
- A61K 2239/28: Expressing multiple CARs, TCRs or antigens
- C07K 2317/21: from primates, e.g. man
- C07K 2317/31: multispecific
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/64: comprising a combination of variable region and constant region components
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K 2319/70: containing domain for protein-protein interaction
- 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

Provided are CCT5-binding molecules, including anti-CCT5 antibodies and antigen-binding fragments thereof such as heavy chain variable (VH) regions and single-chain antibody fragments, and conjugates comprising the anti-CCT5 binding molecules such as immunoconjugates and antibody-drug conjugates, and chimeric receptors comprising the anti-CCT5 binding molecules such as chimeric antigen receptors (CARs). In some embodiments, the anti-CCT5 antibodies or antigen-binding fragments thereof specifically bind to CCT5. Also provided are genetically engineered cells expressing the CARs or CCT5-binding molecules and uses thereof such as in adoptive cell therapy.

## Claims

### Claim 1

An antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment binds to a peptide sequence comprising the sequence TSVEDYKA (SEQ ID NO:70), SSVEAFKR (SEQ ID NO:71) or DSVEAIKA (SEQ ID NO:72), and wherein the antibody or antigen-binding fragment comprises
a heavy chain variable (VH) region comprising the amino acid sequence set forth in SEQ ID NO:1; and
a light chain variable (VL) region comprising the amino acid sequence set forth in SEQ ID NO:2.

### Claim 2 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the antigen-binding fragment comprises an scFv.

### Claim 3

An antibody or antigen-binding fragment thereof that specifically binds to a chaperonin containing TCP1 subunit 5 (CCT5) protein comprising:
a heavy chain variable (VH) region comprising a heavy chain complementarity determining region 1 (CDR-H1), a CDR-H2, and a CDR-H3, respectively, comprising the amino acid sequences of CDR-H1, CDR-H2, and CDR-H3 sequences contained within the VH region amino acid sequence set forth in SEQ ID NO: 1; and
a light chain variable (VL) region comprising a light chain complementarity determining region 1 (CDR-L1), a CDR-L2, and a CDR-L3, respectively, comprising the amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 sequences contained within the light chain variable (VL) region amino acid sequence set forth in SEQ ID NO: 2.

### Claim 4 (depends on 3)

The antibody or antigen-binding fragment thereof of claim 3, wherein:
the VH region comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:11; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 12; and a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 13; and
the VL region comprises a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:21; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 22; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 23.

### Claim 5 (depends on 3)

A chimeric antigen receptor (CAR) comprising an extracellular portion comprising the antibody or antigen-binding fragment thereof of claim 3, a transmembrane domain, and an intracellular signaling region.

### Claim 6 (depends on 3)

The antibody or antigen-binding fragment thereof of claim 3, wherein the antigen-binding fragment comprises an scFv.

### Claim 7 (depends on 3)

The antibody or antigen-binding fragment thereof of claim 3, wherein the antibody is a bispecific antibody that further specifically binds to a second antigen.

### Claim 8

An antibody or antigen-binding fragment thereof that specifically binds to a chaperonin containing TCP1 subunit 5 (CCT5) protein, wherein the antibody or antigen-binding fragment comprises:
a heavy chain variable (VH) region comprising a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:11; a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 12; and a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:13; and
a light chain variable (VL) region comprising a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:21; a CDR-L2 comprising the amino acid sequence set forthin SEQ ID NO: 22; and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 23.

### Claim 9 (depends on 8)

The antibody or antigen-binding fragment thereof of claim 8, wherein the antibody or antigen-binding fragment comprises a heavy chain variable (VH) region having at least 95% sequence identity to the VH region amino acid sequence set forth in SEQ ID NO:1; and a light chain variable (VL) region having at least 95% sequence identity to the VL region amino acid sequence set forth in SEQ ID NO:2.

### Claim 10 (depends on 8)

The antibody or antigen-binding fragment of claim 8, wherein the VH and VL regions of the antibody or antigen-binding fragment thereof comprise the amino acid sequences of SEQ ID NOs: 1 and 2, respectively.

### Claim 11 (depends on 8)

The antibody or antigen-binding fragment of claim 8, wherein the antigen-binding fragment comprises an scFv.

### Claim 12 (depends on 11)

The antibody or antigen-binding fragment of claim 11, wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO:52.

### Claim 13 (depends on 8)

The antibody or antigen-binding fragment of claim 8, wherein the antibody is a bispecific antibody that further specifically binds to a second antigen.

### Claim 14 (depends on 13)

The antibody or antigen-binding fragment of claim 13, wherein the second antigen is expressed on a tumor cell or a T cell.

### Claim 15 (depends on 8)

A single chain cell-surface protein, comprising the antibody or antigen-binding fragment thereof of claim 8.

### Claim 16 (depends on 15)

The single chain cell-surface protein of claim 15, wherein the antibody or antigen-binding fragment thereof is an scFv, and wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO: 52.

### Claim 17 (depends on 8)

A conjugate comprising the antibody or antigen-binding fragment thereof of claim 8 and a heterologous molecule or moiety.

### Claim 18 (depends on 17)

The conjugate of claim 17, wherein the heterologous molecule or moiety is a protein, peptide, nucleic acid, or small molecule.

### Claim 19 (depends on 8)

A chimeric antigen receptor (CAR) comprising an extracellular portion comprising the antibody or antigen-binding fragment thereof of claim 8, a transmembrane domain, and an intracellular signaling region.

### Claim 20 (depends on 19)

The chimeric antigen receptor of claim 19, wherein the extracellular portion comprises an antigen-binding fragment and the antigen-binding fragment is an scFv.

### Claim 21 (depends on 20)

The chimeric antigen receptor of claim 20, wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO: 52.

### Claim 22 (depends on 19)

The chimeric antigen receptor of claim 19, wherein the intracellular signaling region is or comprises a primary signaling domain, a signaling domain that is capable of inducing a primary activation signal in a T cell, a signaling domain of a T cell receptor (TCR) component, and/or a signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM).

### Claim 23 (depends on 19)

The chimeric antigen receptor of claim 19, wherein the intracellular signaling region is or comprises a CD3-zeta (CD3) chain.

### Claim 24 (depends on 19)

The chimeric antigen receptor of claim 19, wherein the transmembrane domain comprises a transmembrane portion of CD28.

### Claim 25 (depends on 19)

The chimeric antigen receptor of claim 19, wherein the intracellular signaling region further comprises a costimulatory signaling domain.

### Claim 26 (depends on 25)

The chimeric antigen receptor of claim 25, wherein the costimulatory signaling domain comprises an intracellular signaling domain of a CD28, a 4-1BB or an ICOS or a signaling portion thereof.

### Claim 27 (depends on 8)

An engineered cell expressing a receptor comprising the antibody or antigen-binding fragment thereof of claim 8.

### Claim 28 (depends on 8)

A composition comprising the antibody or antigen-binding fragment thereof of claim 8 and a pharmaceutically acceptable carrier.