Claims for Patent: 9,499,622

Summary for Patent: 9,499,622

Title:	Anti-EGFR/anti-HER2 bispecific antibodies with anti-EGFR DARPins
Abstract:	An anti-EGFR/anti-HER2 bispecific antibody including an anti-EGFR DARPin and an anti-HER2 antibody, a pharmaceutical composition including the bispecific antibody, a method of preparing the bispecific antibody, and a method of reducing a side effect and/or enhancing efficacy of an anti-HER2 antibody using an anti-EGFR DARPin.
Inventor(s):	Cheong; Kwang Ho (Seoul, KR), Lee; Seung Hyun (Suwon-si, KR), Lin; Powei (Hwaseong-si, KR), Lee; Saet Byoul (Seoul, KR), Hwang; Jae Woong (Seoul, KR)
Assignee:	SAMSUNG ELECTRONICS CO., LTD. (Suwon-Si, KR)
Application Number:	14/625,296
Patent Claims:	1. An anti-EGFR/anti-HER2 bispecific antibody comprising: an anti-EGFR DARPin, and an anti-HER2 antibody, wherein the anti-HER2 antibody is an IgG antibody or an scFv-Fc antibody, or a combination thereof. 2. The bispecific antibody of claim 1, wherein the anti-EGFR DARPin comprises at least one of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4, and wherein at least one EGFR DARPin is, optionally, repeated 2 to 10 times. 3. The bispecific antibody of claim 1, wherein the anti-HER2 antibody is (1) trastuzumab, pertuzumab, trastuzumab emtansine, or an anti-HER2 IgG antibody comprising a heavy chain variable region comprising SEQ ID NO: 5 and a light chain variable region comprising SEQ ID NO: 6; or (2) an scFv-Fc antibody comprising an antigen-binding fragment of trastuzumab, pertuzumab, trastuzumab emtansine, or an anti-HER2 IgG antibody comprising a heavy chain variable region comprising SEQ ID NO: 5 and a light chain variable region comprising SEQ ID NO: 6. 4. A pharmaceutical composition comprising the anti-EGFR/anti-HER2 bispecific antibody of claim 1. 5. A method of treating a cancer in a subject, comprising administering the anti-EGFR/anti-HER2 bispecific antibody of claim 1 to the subject, wherein the cancer is characterized by the expression of EGFR and HER2. 6. A method of preparing an anti-EGFR/anti-HER2 bispecific antibody of claim 1, comprising linking an anti-EGFR DARPin, and an anti-HER2 antibody, wherein the anti-HER2 antibody is an IgG antibody, a scFv-Fc antibody, or a combination thereof. 7. The method of claim 6, wherein the anti-EGFR DARPin comprises at least one of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4, and wherein at least one EGFR DARPin is, optionally, repeated 2 to 10 times. 8. The method of claim 6, wherein the anti-HER2 antibody is (1) trastuzumab, pertuzumab, trastuzumab emtansine, or an anti-HER2 IgG antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 5 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 6; or (2) a scFv-Fc antibody comprising an antigen-binding fragment of trastuzumab, pertuzumab, trastuzumab emtansine, or an anti-HER2 IgG antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 5 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 6. 9. A method of enhancing the efficacy of an anti-HER2 antibody, comprising binding an anti-EGFR DARPin to an anti-HER2 antibody, wherein the anti-HER2 antibody is an IgG antibody, an scFv-Fc antibody, or a combination thereof. 10. The method of claim 9, wherein the anti-EGFR DARPin comprises at least one of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4, and wherein at least one DARPin is, optionally, repeated 2 to 10 times. 11. The method of claim 9, wherein the anti-HER2 antibody is (1) trastuzumab, pertuzumab, trastuzumab emtansine, or an anti-HER2 IgG antibody comprising a heavy chain variable region comprising SEQ ID NO: 5 and a light chain variable region comprising SEQ ID NO: 6; or (2) a scFv-Fc antibody comprising an antigen-binding fragment of trastuzumab, pertuzumab, trastuzumab emtansine, or an anti-HER2 IgG antibody comprising a heavy chain variable region comprising SEQ ID NO: 5 and a light chain variable region comprising SEQ ID NO: 6. 12. A nucleic acid encoding the bispecific antibody of claim 1, optionally in a vector. 13. A cell comprising the nucleic acid of claim 12. 14. A method of preparing a bispecific antibody of claim 1 comprising expressing a nucleic acid encoding the bispecific antibody in a cell. 15. The method of claim 5, wherein the subject is a cancer patient having resistance against an EGFR antagonist. 16. The method of claim 5, wherein the subject is a cancer patient having resistance against an anti-HER2 antibody. 17. The method of claim 5, wherein the subject is a cancer patient having resistance against an EGFR antagonist and an anti-HER2 antibody. 18. The antibody of claim 1, wherein treatment of a gastric cancer cell with the antibody causes internalization of HER2 and EGFR. 19. The method of claim 5, wherein the antibody causes internalization of HER2 and EGFR.

Details for Patent 9,499,622

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2034-02-18
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2034-02-18
Genentech, Inc.	PERJETA	pertuzumab	Injection	125409	06/08/2012		2034-02-18