# US 10,118,972 B2 · Anti-HER2 antibody-drug conjugate

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- Number: US 10,118,972 B2
- Document ID: US10118972B2
- Status: Granted
- Kind: B2
- Application number: 15/221,851
- Filed: 2016-07-28
- Published: 2016-11-17
- Granted: 2018-11-06
- Earliest claimed: 2014-01-31
- Assignees: Daiichi Sankyo Company, Limited
- Applicants: Daiichi Sankyo Company, Limited
- Inventors: Hiroyuki Naito; Yusuke Ogitani; Takeshi Masuda; Takashi Nakada; Masao Yoshida; Shinji Ashida; Koji Morita; Hideki Miyazaki; Yuji Kasuya; Ichiro Hayakawa; Yuki Abe
- Web page: https://patentgrep.com/patent/US10118972B2

## CPC

- C07K 16/32: against translation products of oncogenes
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 47/486
- A61K 47/48384
- A61K 47/48569
- A61K 47/48584
- A61K 47/48592
- A61K 47/48615
- A61K 47/48638
- A61K 47/48715
- C07D 491/22: in which the condensed system contains four or more hetero rings
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/30: from tumour cells
- C07K 16/303: {Liver or Pancreas}
- C07K 16/3015: {Breast}
- C07K 16/3023: {Lung}
- C07K 16/3046: {Stomach, Intestines}
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- C07D 491/052: the oxygen-containing ring being six-membered
- 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)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

As an antitumor drug which is excellent in terms of antitumor effect and safety and has an excellent therapeutic effect, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an anti-HER2 antibody via a linker having a structure represented by the following formula: -L1-L2-LP-NH—(CH2)n1-La-(CH2)n2-C(═O)— wherein the anti-HER2 antibody is connected to the terminal L1, and the antitumor compound is connected to the carbonyl group of the —(CH2)n2-C(═O)— moiety with the nitrogen atom of the amino group at position 1 as the connecting position.

## Claims

### Claim 1

An antibody-drug conjugate, wherein a linker and an antitumor compound represented by the following formula and anti-HER2 antibody are connected:
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-GGFG (SEQ ID NO: 3) —NH—CH2—O—CH2—C(═O)—(NH-DX)
wherein
-(Succinimid-3-yl-N)— has a structure represented by the following formula:
which is connected to the antibody at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1, and (NH-DX) represents a group represented by the following formula:
wherein the nitrogen atom of the amino group at position 1 is the connecting position.

### Claim 2 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein an average number of units of the selected one drug-linker structure conjugated per antibody is in a range of from 2 to 8.

### Claim 3 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein an average number of units of the selected one drug-linker structure conjugated per antibody is in a range of from 3 to 8.

### Claim 4 (depends on 1)

A drug containing the antibody-drug conjugate according to claim 1 or a salt thereof.

### Claim 5 (depends on 1)

A pharmaceutical composition containing the antibody-drug conjugate according to claim 1 or a salt thereof as an active component, and a pharmaceutically acceptable formulation component.

### Claim 6 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein the anti-HER2 antibody comprises a heavy chain and a light chain selected from the group:
a heavy chain consisting of an amino acid sequence consisting of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain consisting of an amino acid sequence consisting of amino acid residues 1 to 214 of SEQ ID NO: 2, and
a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2.

### Claim 7 (depends on 6)

The antibody-drug conjugate according to claim 6, wherein the anti-HER2 antibody comprises a heavy chain consisting of the amino acid sequence consisting of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence consisting of amino acid residues 1 to 214 of SEQ ID NO: 2.

### Claim 8 (depends on 6)

The antibody-drug conjugate according to claim 6, wherein the anti-HER2 antibody comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2.