Claims for Patent: 9,669,106

Summary for Patent: 9,669,106

Title:	Conjugate of monomethyl auristatin F and trastuzumab and its use for the treatment of cancer
Abstract:	The present invention relates to an antibody-drug-conjugate or pharmaceutical composition comprising the same. From one aspect, the invention relates to an antibody-drug-conjugate (ADC) comprising an antibody consisting of the Trastuzumab or a biosimilar thereof, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment of cancer comprising administering to the subject an effective amount of said antibody-drug-conjugate or composition comprising the same.
Inventor(s):	Goetsch; Liliane (Ayze, FR), Jouhanneaud; Alexandra (Bonneville, FR), Perez; Michel (Castres, FR)
Assignee:	Pierre Fabre Medicament (Boulogne-Billancourt, FR)
Application Number:	14/923,022
Patent Claims:	1. An antibody-drug-conjugate of the following formula (I): Ab-(L-D).sub.n (I) or a pharmaceutically acceptable salt thereof, wherein Ab is Trastuzumab; L is a linker; D is a drug moiety of the following formula (IIa): ##STR00162## wherein: R.sub.2 is COOH, COOCH.sub.3 or thiazolyl; R.sub.3 is H or (C.sub.1-C.sub.6)alkyl; R.sub.9 is H or (C.sub.1-C.sub.6)alkyl; m is an integer comprised between 1 and 8; the wavy line indicates the point of attachment to L; and n is 1 to 12. 2. The antibody-drug-conjugate of claim 1, wherein D is a drug moiety of the following formula (IIb): ##STR00163## 3. The antibody-drug-conjugate according to claim 1, wherein L is a linker of the following formula (III): ##STR00164## wherein L.sub.2 is (C.sub.4-C.sub.10)cycloalkyl-carbonyl, (C.sub.2-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkyl-carbonyl, W is an amino acid unit; w is an integer comprised between 0 and 5; Y is PAB-carbonyl with PAB being ##STR00165## y is 0 or 1; the asterisk indicates the point of attachment to D; and the wavy line indicates the point of attachment to Ab. 4. The antibody-drug-conjugate according to claim 1, wherein (L-D) is selected from: ##STR00166## wherein the wavy line indicates the point of attachment to Ab. 5. The antibody-drug-conjugate according to claim 1 having a formula selected from: ##STR00167## and the pharmaceutically acceptable salts thereof, wherein Ab is Trastuzumab; and nisi to 12. 6. A composition comprising at least one antibody-drug-conjugate according to claim 1 and a pharmaceutical acceptable excipient. 7. A method for the treatment of a cancer that express Her2 in a subject in need thereof, comprising administering to the subject an effective amount of at least one antibody-drug-conjugate according to claim 1. 8. The method according to claim 7 for the treatment of tumors that are resistant to Tratstuzumab. 9. The method according to claim 8 for the treatment of large tumors. 10. The method according to claim 7, wherein said cancer is selected from breast cancer, gastric cancer and lung cancer. 11. A method for the treatment of a cancer that express Her2 in a subject in need thereof, comprising administering to the subject an effective amount of a composition of claim 6. 12. The method according to claim 11 for the treatment of tumors that are resistant to Tratstuzumab. 13. The method according to claim 11 for the treatment of large tumors. 14. The method according to claim 11 for the treatment of large tumors. 15. The method according to claim 11, wherein said cancer is selected from breast cancer, gastric cancer and lung cancer.

Details for Patent 9,669,106

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2039-02-26
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2039-02-26
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2039-02-26