Stable antibody-drug conjugate, preparation method therefor, and use thereof
The present invention provides a conjugate and preparation method thereof, a pharmaceutical composition comprising the conjugate and use of the pharmaceutical composition in the manufacture of a medicament for the treatment or prevention of a disease.
1. A compound selected from the group consisting of:
wherein n is 3, d represents any one of the integers between 1 and 20, A is anti ErbB2/Her2 antibody, LA3 is Gly-Ala; b is independently 0 or 1, X3 is glutamic acid, x is —OH or —NH2 group.
2. The compound according to claim 1 , wherein A is Trastuzumab, LA3 is Gly-Ala, b is 1, d is 2, 4, or 8, X3 is glutamic acid, x is —NH2 group.
3. A compound selected from the group consisting of:
wherein n is 3, d represents any one of the integers between 1 and 20, A is anti ErbB2/Her2 antibody, LA3 is Gly-Ala; b is independently 0 or 1, X3 is glutamic acid, x is —OH or —NH2 group.
4. The compound according to claim 3 , wherein A is Trastuzumab, LA3 is Gly-Ala, b is 1, d is 2, 4, or 8, X3 is glutamic acid, x is —OH group.
5. A pharmaceutical composition comprising the compound according to claim 3 or any pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
6. The pharmaceutical composition according to claim 5 , in the form of lyophilized powder for injection or injection liquid.
7. A method for inhibiting cell proliferation in an animal, including treating the animal with the compound according to claim 3 .
8. The method according to claim 7 , wherein the animal is a mammal.
9. The method according to claim 8 , wherein the animal is a human.
10. A method for treating a disease in human, including treating the human with the compound according to claim 3 , wherein the said disease is tumor, and wherein the tumor cell surface has a specific antigen or a receptor protein which is ErbB2/Her2.
11. The method according to claim 10 , wherein the tumor is breast cancer, gastric cancer, ovarian cancer, lung cancer, colon cancer, rectal cancer, colorectal cancer or esophageal cancer.
12. A method for inhibiting cell proliferation in an animal, including treating the animal with the compound according to claim 1 .
13. The method according to claim 12 , wherein the animal is a mammal.
14. The method according to claim 13 , wherein the animal is a human.
15. A method for treating a disease in human, including treating the human with the compound according to claim 1 , wherein the said disease is tumor, and wherein the tumor cell surface has a specific antigen or a receptor protein which is ErbB2/Her2.
16. The method according to claim 15 , wherein the tumor is breast cancer, gastric cancer, ovarian cancer, lung cancer, colon cancer, rectal cancer, colorectal cancer or esophageal cancer.
17. A pharmaceutical composition comprising the compound according to claim 1 or any pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
18. The pharmaceutical composition according to claim 17 , in the form of lyophilized powder for injection or injection liquid.