Claims for Patent: 10,011,659

Summary for Patent: 10,011,659

Title:	Compositions and methods for treating cancer resistant to a tyrosine kinase inhibitor (TKI)
Abstract:	Methods of treating a subject having cancer exhibiting a resistance to a tyrosine kinase inhibitor (TKI) are provided. Accordingly, there is provided a method comprising administering to the subject a therapeutically effective amount of antibodies comprising an anti-EGFR antibody, an anti-HER2 antibody and an anti-HER3 antibody. Also provided are compositions and articles of manufacture for treating cancer resistance to a TKI. Also provided are methods of treating non-resistant tumors.
Inventor(s):	Yarden; Yosef (Rehovot, IL), Mancini; Maicol (Rehovot, IL), Gaborit; Nadege (Rehovot, IL)
Assignee:	Yeda Research and Development Co. Ltd. (Rehovot, IL)
Application Number:	14/956,585
Patent Claims:	1. A method of treating a subject having lung cancer exhibiting a resistance to a tyrosine kinase inhibitor (TKI), wherein said TKI is directed to an ErbB family member and wherein cells of the cancer express said ErbB family member, the method comprising administering to the subject a therapeutically effective amount of antibodies comprising an anti-EGFR antibody, an anti-HER2 antibody and an anti-HER3 antibody, wherein: (i) said anti-EGFR antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 15 (CDR1), 16 (CDR2) and 17 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 18 (CDR1), 19 (CDR2) and 20 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone 565, CNCM-4262); (ii) said anti-HER2 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 21 (CDR1), 22 (CDR2) and 23 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 24 (CDR1), 25 (CDR2) and 26 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone N12, CNCM-I-4112); (iii) said anti-HER3 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 27 (CDR1), 28 (CDR2) and 29 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 30 (CDR1), 31 (CDR2) and 32 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone NG33); (iv) said anti-EGFR antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 15 (CDR1), 16 (CDR2) and 17 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 18 (CDR1), 19 (CDR2) and 20 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone 565, CNCM-4262) and said anti-HER2 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 21 (CDR1), 22 (CDR2) and 23 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 24 (CDR1), 25 (CDR2) and 26 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone N12, CNCM-I-4112); (v) said anti-EGFR antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 15 (CDR1), 16 (CDR2) and 17 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 18 (CDR1), 19 (CDR2) and 20 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone 565, CNCM-4262) and said anti-HER3 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 27 (CDR1), 28 (CDR2) and 29 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 30 (CDR1), 31 (CDR2) and 32 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone NG33); (vi) said anti-HER2 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 21 (CDR1), 22 (CDR2) and 23 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 24 (CDR1), 25 (CDR2) and 26 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone N12, CNCM-I-4112); and said anti-HER3 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 27 (CDR1), 28 (CDR2) and 29 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 30 (CDR1), 31 (CDR2) and 32 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone NG33); (vii) said anti-EGFR antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 15 (CDR1), 16 (CDR2) and 17 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 18 (CDR1), 19 (CDR2) and 20 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone 565, CNCM-4262), said anti-HER2 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 21 (CDR1), 22 (CDR2) and 23 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 24 (CDR1), 25 (CDR2) and 26 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone N12, CNCM-I-4112); and said anti-HER3 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 27 (CDR1), 28 (CDR2) and 29 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 30 (CDR1), 31 (CDR2) and 32 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone NG33); (viii) said anti-EGFR antibody comprises cetuximab; and said anti-HER3 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 27 (CDR1), 28 (CDR2) and 29 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 30 (CDR1), 31 (CDR2) and 32 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone NG33); (ix) said anti-HER2 antibody comprises trastuzumab; and said anti-HER3 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 27 (CDR1), 28 (CDR2) and 29 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 30 (CDR1), 31 (CDR2) and 32 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone NG33); and/or (x) said anti-EGFR antibody comprises cetuximab, said anti-HER2 antibody comprises trastuzumab; and said anti-HER3 antibody comprises an antigen recognition domain having complementarity determining region (CDR) amino acid sequences as set forth in: SEQ ID NOs: 27 (CDR1), 28 (CDR2) and 29 (CDR3) (sequentially arranged from N to C on a light chain of said polypeptide) and 30 (CDR1), 31 (CDR2) and 32 (CDR3) (sequentially arranged from N to C on a heavy chain of said polypeptide) (Clone NG33), thereby treating the lung cancer exhibiting resistance to a TKI of an ErbB family member in the subject. 2. The method of claim 1, further comprising administering said TKI to said subject. 3. The method of claim 1, further comprising administering an additional TKI to said subject which is different from said TKI. 4. The method of claim 1, wherein said ErbB family member is EGFR. 5. The method of claim 1, wherein said TKI is selected from the group consisting of erlotinib, gefitinib and lapatinib. 6. The method of claim 1, wherein said lung cancer is a non-small cell lung cancer (NSCLC). 7. The method of claim 1, wherein said cells of said cancer express an ErbB receptor having a mutation in a kinase domain of said receptor. 8. The method of claim 7, wherein said mutation does not substantially affect a kinase activity of said ErhB as compared to said kinase activity of said ErbB devoid of said mutation. 9. The method of claim 7, wherein said ErbB is EGFR. 10. The method of claim 9, wherein said mutation comprises a substitution of Threonine to Methionine at position 790 (T790M) or a Cysteine to Serine at position 797 (C797S). 11. The method of claim 1, further comprising subjecting the subject to a therapy selected from the group consisting of a radiotherapy and a chemotherapy. 12. The method of claim 1, wherein said administering comprises multiple administrations. 13. The method of claim 12, wherein said multiple administrations comprise bi-weekly administrations. 14. The method of claim 1, wherein said antibodies are selected causing at least 50% reduction in tumor volume as compared to a control in a xenograft mouse model. 15. The method of claim 1, wherein said resistance is acquired resistance.

Details for Patent 10,011,659

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2034-09-08
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2034-09-08
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2034-09-08
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2034-09-08
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2034-09-08