Drug conjugate comprising drug linked to human c-Met antibody, and use therefor

Patent metadata

Field	Value
Publication number	US-9364556-B2
Application number	US-201214360937-A
Country	US
Kind code	B2
Filing date	Nov 28, 2012
Priority date	Nov 28, 2011
Publication date	Jun 14, 2016
Grant date	Jun 14, 2016

Abstract

The present invention relates to a drug conjugate comprising a cytotoxic drug conjugated to a c-Met specific human antibody. More specifically, the present invention relates to: a drug conjugate comprising a cytotoxic drug conjugated to a c-Met specific human antibody; a pharmaceutical composition for cancer treatment comprising the drug conjugate; and a cancer treatment method comprising a step in which the drug conjugate or pharmaceutical composition is administered to an individual.

First claim

What is claimed is:

1. An antibody-drug conjugate comprising a cytotoxic, drug conjugated to a c-Met-specific human antibody, wherein the antibody comprises:
a heavy-chain variable region comprising:
i) a heavy-chain CDR1 comprising amino acids having the sequence set forth it SEQ ID NO: 1;
ii) a heavy-chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 2; and
iii) a heavy-chain CDR3 comprising amino acids having the sequence set forth SEQ ID NO: 3; and
a light-chain variable region comprising:
i) a light-chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 4;
ii) a light-chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 5; and
iii) a light-chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 6.

2. The antibody-drug conjugate of claim 1 , wherein the heavy-chain variable region of the human antibody further comprises cysteine.

3. The antibody-drug conjugate of claim 1 , wherein the human antibody is an agonistic antibody against c-Met.

4. The antibody-drug conjugate of claim 1 , wherein the human antibody comprises a heavy-chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 7 or 8 and a light-chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 11.

5. The antibody-drug conjugate of claim 1 , wherein the human antibody comprises a heavy-chain constant region comprising amino acids having the sequence set forth in SEQ ID NO: 13 and a light-chain constant region comprising amino acids having the sequence set forth in SEQ ID NO: 15.

6. The antibody-drug conjugate of claim 1 , wherein the cytotoxic, drug is conjugated to the human antibody by a linker.

7. The antibody-drug conjugate of claim 6 , wherein the linker is a hydrazone or a peptide linker.

8. The antibody-drug conjugate of claim 1 , wherein the cytotoxic drug is conjugated to the human antibody by a Schiff base.

9. The antibody-drug conjugate of claim 6 , wherein the cytotoxic drug is conjugated to the human antibody by [linker-Val (valine)-Cit (citrulline)] or [linker-Schiff base].

10. The antibody-drug conjugate of claim 1 , wherein the cytotoxic drug is selected from the group consisting of doxorubicin, carboplatin (paraplatin), cisplatin, cyclophosphamide, ifosfamide, nidran, nitrogen mustard (mechlorethamine HCL), Neomycin, mitomycin C, cytarabine, flurouracil, gemcitabine, trimetrexate, methotrexate, etoposide, vinblastine, vinorelbine, alimta, altretamine, procarbazine, taxol, taxotere, topotecan and irinotecan.

11. A pharmaceutical composition for treating cancer that expresses c-Met, which comprises the antibody-drug conjugate of claim 1 .

12. The pharmaceutical composition of claim 11 , wherein the cancer is a hypoxic tumor.

13. The pharmaceutical composition of claim 11 , wherein the conjugate is internalized into cells by endocytosis.

14. The pharmaceutical composition of claim 11 , wherein the cytotoxic drug of the conjugate is separated either by intracellular protease or under an intracellular acidic condition.

15. A method for treating cancer that expresses c-Met, which comprises administering the antibody-drug, conjugate of claim 1 to a subject.

16. A method for treating cancer that expresses c-Met, which comprises administering the pharmaceutical composition of claim 11 to a subject.

Assignees

• Korea Res Inst Of Bioscience
• A&Rt Co Ltd

Inventors

• Park Young Woo
• Jo Ki Won
• Jo Sun Jeong
• Hyun Soon Sil
• Park Jae Eun
• Yoo Seok Ho
• Jang Myeoung Hee
• Kim Hye Nan
• Park Chan Woong

Classifications

• A61K31/704 Primary

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/2863

  against receptors for growth factors, growth regulators · CPC title

• A61K47/48561

  Human Necessities · mapped topic

• A61K47/48407 Primary

  Human Necessities · mapped topic