# US 2020/0399397 A1 · Anti-her2 antibody or antigen-binding fragment thereof, and chimeric antigen receptor comprising same

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

- Number: US 2020/0399397 A1
- Document ID: US20200399397A1
- Status: Published application
- Kind: A1
- Application number: 16/881,650
- Filed: 2020-05-22
- Published: 2020-12-24
- Earliest claimed: 2017-11-14
- Assignees: Green Cross Lab Cell Corporation
- Applicants: Green Cross Lab Cell Corporation
- Inventors: Jong Seo LEE; Kyu Tae KIM; Young Ha LEE; In Sik HWANG; Bong Kook KO; Eunji CHOI; You-Sun KIM; Jeongmin KIM; Miyoung JUNG; Hoyong LIM; Sungyoo CHO
- Web page: https://patentgrep.com/patent/US20200399397A1

## CPC

- C07K 16/32: against translation products of oncogenes
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 40/15: Natural-killer [NK] cells; Natural-killer T [NKT] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/4205: {Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4}
- A61P 35/00: Antineoplastic agents
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C12N 5/0646: {Natural killers cells [NK], NKT cells}
- 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 2039/505: {comprising antibodies}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/49: Breast
- A61K 2239/53: Liver
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/03: containing a transmembrane segment
- C12N 2510/00: Genetically modified cells
- 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 disclosure relates to a novel anti-HER2 antibody or an antigen-binding fragment thereof used in the prevention or treatment of cancer, a chimeric antigen receptor including the same, and uses thereof. The antibody of the present disclosure is an antibody that specifically binds to HER2 which is highly expressed in cancer cells (particularly, breast cancer or gastric cancer cells), and binds to an epitope that is different from an epitope to which trastuzumab binds.

## Claims

### Claim 1

An antibody against HER2 (human epidermal growth factor receptor 2) comprising any one of (a) to (e), or an antigen-binding fragment thereof:
(a) a heavy chain variable region comprising CDRH1 of SEQ ID NO 1, CDRH2 of SEQ ID NO 2 and CDRH3 of SEQ ID NO 3, and a light chain variable region comprising CDRL1 of SEQ ID NO 4, CDRL2 of SEQ ID NO 5 and CDRL3 of SEQ ID NO 6;
(b) a heavy chain variable region comprising CDRH1 of SEQ ID NO 7, CDRH2 of SEQ ID NO 8 and CDRH3 of SEQ ID NO 9, 71 or 72, and a light chain variable region comprising CDRL1 of SEQ ID NO 10, CDRL2 of SEQ ID NO 11 and CDRL3 of SEQ ID NO 12, 73 or 74;
(c) a heavy chain variable region comprising CDRH1 of SEQ ID NO 13, CDRH2 of SEQ ID NO 14 and CDRH3 of SEQ ID NO 15, and a light chain variable region comprising CDRL1 of SEQ ID NO 16, CDRL2 of SEQ ID NO 17 and CDRL3 of SEQ ID NO 18;
(d) a heavy chain variable region comprising CDRH1 of SEQ ID NO 19, CDRH2 of SEQ ID NO 20 and CDRH3 of SEQ ID NO 21, and a light chain variable region comprising CDRL1 of SEQ ID NO 22, CDRL2 of SEQ ID NO 23 and CDRL3 of SEQ ID NO 24; and
(e) a heavy chain variable region comprising CDRH1 of SEQ ID NO 25, CDRH2 of SEQ ID NO 26 and CDRH3 of SEQ ID NO 27, and a light chain variable region comprising CDRL1 of SEQ ID NO 28, CDRL2 of SEQ ID NO 29 and CDRL3 of SEQ ID NO 30.

### Claim at position 2

-6. (canceled)

### Claim 7

A chimeric antigen receptor polypeptide comprising:
(a) an HER2-binding domain;
(b) a transmembrane domain (TM);
(c) a costimulatory domain; and
(d) an intracellular signaling domain (ICD).

### Claim at position 4

-23. (canceled)

### Claim 24

A chimeric antigen receptor comprising an extracellular domain that binds Her2, wherein the extracellular domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 113 (hz39D2 (VL-GS linker-VH)).

### Claim 25 (depends on 24)

The chimeric antigen receptor of claim 24, wherein the extracellular domain comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 113 (hz39D2 (VL-GS linker-VH)).

### Claim 26 (depends on 24)

The chimeric antigen receptor of claim 24, wherein the extracellular domain comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 113 (hz39D2 (VL-GS linker-VH)).

### Claim 27 (depends on 24)

The chimeric antigen receptor of claim 24, wherein the extracellular domain comprises SEQ ID NO: 113 (hz39D2 (VL-GS linker-VH)).

### Claim 28 (depends on 24)

The chimeric antigen receptor of claim 24, further comprising
an extracellular signaling domain linked to the extracellular domain;
a hinge domain linked to the extracellular domain;
a transmembrane domain linked to the hinge domain; and
an intracellular stimulatory signal linked to the hinge domain.

### Claim 29 (depends on 28)

The chimeric antigen receptor of claim 28, wherein the extracellular signaling domain comprises an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 111 (CD8α signal peptide).

### Claim 30 (depends on 29)

The chimeric antigen receptor of claim 29, wherein the extracellular signaling domain comprises SEQ ID NO: 111 (CD8α signal peptide).

### Claim 31 (depends on 30)

The chimeric antigen receptor of claim 30, wherein the hinge domain comprises an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 115 (CD8α hinge).

### Claim 32 (depends on 31)

The chimeric antigen receptor of claim 31, wherein the hinge domain comprises SEQ ID NO: 115 (CD8α hinge).

### Claim 33 (depends on 32)

The chimeric antigen receptor of claim 32, wherein the transmembrane domain comprises an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 117 (CD8α TM) or SEQ ID NO: 119 (CD28 TM).

### Claim 34 (depends on 33)

The chimeric antigen receptor of claim 33, wherein the transmembrane domain comprises SEQ ID NO: 117 CD8α TM) or SEQ ID NO: 119 (CD28 TM).

### Claim 35 (depends on 34)

The chimeric antigen receptor of claim 34, wherein the intracellular stimulatory signal comprises an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 121 (CD3-ζ).

### Claim 36 (depends on 35)

The chimeric antigen receptor of claim 35, wherein the intracellular stimulatory signal comprises SEQ ID NO: 121 (CD3-ζ).

### Claim 37 (depends on 36)

The chimeric antigen receptor of claim 36, further comprising a second intracellular stimulatory signal, wherein the second intracellular stimulatory signal comprises an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 123 (4-1BB) or SEQ ID NO: 125 (CD28).

### Claim 38 (depends on 37)

The chimeric antigen receptor of claim 37, wherein the second intracellular stimulatory signal comprises SEQ ID NO: 123 (4-1BB) or SEQ ID NO: 125 (CD28).

### Claim 39 (depends on 38)

The chimeric antigen receptor of claim 38, further comprising a third intracellular stimulatory signal, wherein the third intracellular stimulatory signal comprises an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 127 (OX40L).

### Claim 40 (depends on 39)

The chimeric antigen receptor of claim 39, wherein the third intracellular stimulatory signal comprises SEQ ID NO: 127 (OX40L).

### Claim 41 (depends on 28)

The chimeric antigen receptor of claim 28, wherein the chimeric antigen receptor comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 129 (Clone 2), SEQ ID NO: 131 (Clone 3), SEQ ID NO: 133 (Clone 6), or SEQ ID NO: 135 (Clone 14).

### Claim 42 (depends on 28)

The chimeric antigen receptor of claim 28, wherein the chimeric antigen receptor comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 129 (Clone 2), SEQ ID NO: 131 (Clone 3), SEQ ID NO: 133 (Clone 6), or SEQ ID NO: 135 (Clone 14).

### Claim 43 (depends on 28)

The chimeric antigen receptor of claim 28, wherein the chimeric antigen receptor comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 129 (Clone 2), SEQ ID NO: 131 (Clone 3), SEQ ID NO: 133 (Clone 6), or SEQ ID NO: 135 (Clone 14).

### Claim 44 (depends on 28)

The chimeric antigen receptor of claim 28, wherein the chimeric antigen receptor comprises SEQ ID NO: 129 (Clone 2), SEQ ID NO: 131 (Clone 3), SEQ ID NO: 133 (Clone 6), or SEQ ID NO: 135 (Clone 14).

### Claim 45 (depends on 24)

A nucleic acid molecule encoding the chimeric antigen receptor of claim 24.

### Claim 46 (depends on 45)

A vector comprising the nucleic acid molecule of claim 45.

### Claim 47 (depends on 24)

An immune cell expressing the chimeric antigen receptor of claim 24.

### Claim 48 (depends on 47)

The immune cell of claim 47, wherein the immune cell is a natural killer cell.

### Claim 49 (depends on 48)

A pharmaceutical composition comprising the immune cell of claim 48 and a pharmaceutically acceptable carrier.

### Claim 50 (depends on 49)

A method for treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 49.

### Claim 51 (depends on 50)

The method of claim 50, wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, gastric cancer, lung cancer, liver cancer, bronchial cancer, nasopharyngeal cancer, laryngeal cancer, pancreatic cancer, bladder cancer, colorectal cancer, colon cancer, cervical cancer, brain cancer, prostate cancer, bone cancer, head and neck cancer, skin cancer, thyroid cancer, parathyroid cancer and ureteral cancer.

### Claim 52 (depends on 7)

The chimeric antigen receptor of claim 7, wherein the intracellular signaling domain comprises a functional signaling domain of OX40 ligand.