Granted Patent B2

US 10,786,578 · App. 15/329,818 · Granted Sep 29, 2020

Inventors: Tinya Abrams (Acton, MA); Steven Bruce Cohen (San Diego, CA); Dylan Daniel (San Francisco, CA); Catrin Finner (Planegg, DE); Bernhard Hubert Geierstanger (Solana Beach, CA); Thomas Huber (Basel, CH); William Mallet (Redwood City, CA); Matthew John Meyer (Framingham, MA); Weijia Ou (San Diego, CA); Siew Ho Schleyer (Emeryville, CA); Kathrin Ulrike Tissot-Daguette (Planegg, DE)

Assignee: Novartis AG

A61K47/6803A61K39/39558A61K47/6849A61K49/00A61K51/103A61K51/1093A61P35/02C07K16/2803A61K2039/505A61K2039/545C07K2317/21C07K2317/24C07K2317/33C07K2317/34C07K2317/55C07K2317/565C07K2317/77C07K2317/92

Abstract

Claims (17)

1. An antibody drug conjugate of the formula:

or a pharmaceutically acceptable salt thereof; wherein;

n is an integer from 1 to 10 and antibody (antiB) is an antibody or antigen binding fragment thereof that specifically binds to human cKIT at domains 1-3 (SEQ ID NO:173), comprising:

a heavy chain variable region that comprises (a) a HCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO: 76, (b) a HCDR2 of SEQ ID NO: 77, (c) a HCDR3 of SEQ ID NO: 78;

and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 85, (e) a LCDR2 of SEQ ID NO: 86, and (f) a LCDR3 of SEQ ID NO: 87.

2. The antibody drug conjugate of claim 1 , wherein said antibody or antigen binding fragment thereof comprises:

a heavy chain variable region (VH) that comprises (a) SEQ ID NO: 82, and a light chain variable region (VL) that comprises: (b) SEQ ID NO: 91.

3. The antibody drug conjugate of claim 2 that retains at least 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% identity over either the variable light chain or variable heavy chain region.

4. The antibody drug conjugate of claim 1 , wherein the antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, a single chain antibody (scFv) or an antigen binding fragment.

5. The antibody drug conjugate of claim 1 , wherein said n is an integer from 2 to 8.

6. The antibody drug conjugate of claim 1 , wherein said n is an integer from 3 to 4.

7. The antibody drug conjugate of claim 1 in combination with another therapeutic agent.

8. The antibody drug conjugate of claim 1 in combination with imatinib, sunitinib, NVP-LCL16, NVP-BEZ235, NVP-BKM120, NVP-BYL719, NVP-CCG168, everolimus, NVP-HSP990 or NVP-BVB808.

9. The antibody drug conjugate of claim 1 , wherein the antibody contains at least one non-native cysteine introduced into a constant region, and a linker is attached to the non-native cysteine.

10. The antibody drug conjugate of claim 9 , wherein the at least one non-native cysteine introduced into the constant region is selected from the group consisting of SEQ ID NO: 185, SEQ ID NO:186, SEQ ID NO:187 and SEQ ID NO:188.

11. A pharmaceutical composition comprising the antibody drug conjugate of claim 1 and a pharmaceutically acceptable carrier.

12. The pharmaceutical composition of claim 11 wherein said composition is prepared as a lyophilisate.

Assignments (12)

Continuity (2)