Claims for Patent: 10,092,659

Summary for Patent: 10,092,659

Title:	Duocarmycin ADCs for use in treatment of endometrial cancer
Abstract:	The present invention relates to duocarmycin-containing antibody-drug conjugates (ADCs) for use in the treatment of human solid tumors expressing HER2, wherein the human solid tumor expressing HER2 is endometrial cancer, in particular uterine serous carcinoma (USC). In particular, the present invention relates to duocarmycin-containing ADCs for use in the treatment of endometrial cancer, notably USC, with HER2 IHC 2- or 1+ and HER2 FISH negative tumor tissue status.
Inventor(s):	Santin; Alessandro Davide (New Haven, CT), Goedings; Peter Johannes (Nijmegen, NL)
Assignee:	Synthon Biopharmaceuticals B.V. (Nijmegen, NL) Yale University (New Haven, CT)
Application Number:	15/216,366
Patent Claims:	1. A method of treating endometrial cancer expressing HER2 in a human patient, comprising administering to said patient a therapeutically effective amount of a compound of formula (I) ##STR00011## wherein anti-HER2 Ab is an anti-HER2 antibody or an anti-HER2 antibody fragment able to bind HER2, n is 0, 1, 2, or 3, m represents an average DAR of from 1 to 4, R.sup.1 is selected from the group consisting of ##STR00012## y is 1-16, and R.sup.2 is selected from the group consisting of ##STR00013## 2. The method of claim 1, wherein the endometrial cancer is uterine serous carcinoma. 3. The method of claim 1, wherein the endometrial cancer is HER2 IHC 3+. 4. The method of claim 1, wherein anti-HER2 Ab is an anti-HER2 antibody or an anti-HER2 antibody fragment able to bind HER2, n is 0 or 1, m represents an average DAR of from 1 to 4, R.sup.1 is selected from the group consisting of ##STR00014## y is 1-16, and R.sup.2 is ##STR00015## 5. The method of claim 4, wherein anti-HER2 Ab is an anti-HER2 monoclonal antibody, n is 0 or 1, m represents an average DAR of from 2 to 3, R.sup.1 is ##STR00016## y is 1, 2, 3 or 4, and R.sup.2 is ##STR00017## 6. The method of claim 5, wherein the anti-HER2 Ab is trastuzumab. 7. The method of claim 6, wherein the compound of formula (I) has an average DAR of from 2.5 to 2.9. 8. The method of claim 1, wherein the method comprises administering a compound of formula (II) ##STR00018## 9. The method of claim 8, wherein the compound of formula (II) has an average DAR of from 2.5 to 2.9. 10. The method of claim 8, wherein the compound of formula (II) is administered in an amount of from about 0.3 mg/kg to about 10 mg/kg. 11. The method of claim 10, wherein the compound of formula (II) is administered every three weeks. 12. The method of claim 9, wherein the compound of formula (II) has an average DAR of from 2.6 to 2.9. 13. The method of claim 12, wherein the compound of formula (II) is administered in an amount of from about 0.3 mg/kg to about 10 mg/kg. 14. The method of claim 13, wherein the compound of formula (II) is administered every three weeks. 15. The method of claim 1, further comprising administering an effective amount of a therapeutic antibody or a chemotherapeutic agent, or a combination thereof. 16. The method of claim 15, wherein the endometrial cancer is uterine serous carcinoma. 17. The method of claim 15, wherein the therapeutic antibody is pertuzumab and the chemotherapeutic agent is a taxane, an anthracycline or a tyrosine kinase inhibitor. 18. The method of claim 17, wherein the taxane is docetaxel or paclitaxel, the anthracycline is doxorubicin, epirubicin, daunorubicin, or valrubicin, and the tyrosine kinase inhibitor is afatinib. 19. The method of claim 1, wherein the patient is administered a pharmaceutical composition, comprising the compound of formula (I) and one or more pharmaceutically acceptable excipients. 20. The method of claim 19, wherein the pharmaceutical composition is suitable for intravenous infusion. 21. The method of claim 19, wherein the pharmaceutical composition is in the form of a lyophilized powder or a frozen solution. 22. A method of treating endometrial cancer expressing HER2 in a human patient, comprising administering to said patient a therapeutically effective amount of a compound having the structure ##STR00019## wherein 2.5-2.9 represents an average DAR for the compound. 23. The method of claim 22, wherein the average DAR for the compound is from 2.6 to 2.9.

Details for Patent 10,092,659

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2034-01-10
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2034-01-10
Genentech, Inc.	PERJETA	pertuzumab	Injection	125409	06/08/2012		2034-01-10
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2034-01-10