Use of anti-HER2 antibody-drug conjugate in treating urothelial carcinoma

1 . A method for treating urothelial carcinoma, comprising

administering an antibody-drug conjugate (ADC) to a subject in need thereof, wherein the antibody-drug conjugate is an anti-HER2 antibody or a functional fragment thereof coupled to a cytotoxic molecule;

wherein the ADC is represented by formula Ab-(L-U)n, wherein Ab is the antibody or the functional fragment thereof, L is a linker, U is a conjugated cytotoxic molecule, and n is an integer from 1 to 8, representing the number of therapeutic agent molecules bound to the antibody;

wherein the anti-HER2 antibody or the functional fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein (i) the heavy chain variable region comprises three CDRs, wherein the amino acid sequences of the CDRs are respectively set forth in SEQ ID NO: 1, 2 and 3, and the light chain variable region comprises three CDRs, wherein the amino acid sequences of the CDRs are respectively set forth in SEQ ID NO: 4, 5 and 6;

wherein the linker L is a maleimidocaproyl valine citrulline p-amino-benzyl (mc-vc-pAB) linker; and

wherein the conjugated cytotoxic molecule U is MMAE; and

wherein administration of the ADC to the subject results in a partial remission (PR) or stable disease (SD).

2 . The method according to claim 1 , wherein the cytotoxic molecule is conjugated to the antibody through site-directed or undirected conjugation.

3 . The method according to claim 1 , wherein the antibody or the functional fragment thereof is a murine or chimeric antibody or fragment.

4 . The method according to claim 1 , wherein the antibody or the functional fragment thereof is derived from the antibody secreted by the hybridoma deposited at the China General Microbiological Culture Collection Center of China Committee for Culture Collection of Microorganisms on Aug. 22, 2013, with an accession number of CGMCC No. 8102.

5 . The method according to claim 1 , wherein the antibody or functional fragment thereof is a humanized antibody or fragment.

6 . The method according to claim 5 , wherein the antibody is the antibody secreted by CHO cells deposited at the China Center for Type Culture Collection on Nov. 6, 2013, with an accession number of CCTCC C2013170.

7 . The method according to claim 1 , wherein the urothelial carcinoma is selected from the group consisting of locally developed urothelial carcinoma which cannot be removed by surgery, locally advanced or metastatic urothelial carcinoma, HER2-positive urothelial carcinoma and HER2-positive locally advanced or metastatic urothelial carcinoma.

8 . The method according to claim 7 , wherein the urothelial carcinoma is locally developed urothelial carcinoma which cannot be removed by surgery.

9 . The method according to claim 7 , wherein the urothelial carcinoma is locally advanced or metastatic urothelial carcinoma.

10 . The method according to claim 7 , wherein the urothelial carcinoma is HER2-positive urothelial carcinoma.

11 . The method according to claim 7 , wherein the urothelial carcinoma is HER2-positive locally advanced or metastatic urothelial carcinoma.

12 . The method according to claim 1 , wherein the antibody-drug conjugate further comprises a pharmaceutically acceptable carrier.

13 . The method according to claim 12 , wherein the antibody-drug conjugate is in a form of a lyophilized formulation or a liquid formulation.

14 . The method according to claim 12 , wherein the pharmaceutically acceptable carrier comprises one or more of: a stabilizer, a protective agent, a buffer, a lyoprotectant, an activity protective agent, a surfactant, an adsorption carrier, and an absorption promoter.

15 . The method according to claim 1 , wherein the antibody-drug conjugate is administered intranasally, subcutaneously, intradermally, intramuscularly, or intravenously.

16 . The method according to claim 1 , wherein administration of the ADC to the subject results in a partial remission (PR).

17 . The method according to claim 1 , wherein administration of the ADC to the subject does not result in a serious adverse event (SAE).