Claims for Patent: 10,208,129

Summary for Patent: 10,208,129

Title:	Antibodies selective for cells presenting ErbB2 at high density
Abstract:	An erbB2 antibody is provided that binds preferentially to disease cells having an erbB2 density greater than a normal erbB2 density. The erbB2 antibody comprises a heavy chain and a light chain. Each chain has a constant region and a variable region. Each variable region comprises framework regions and complementarity determining regions (CDRs), wherein the CDRs have an amino acid sequence set forth below: For the heavy chain: CDR1 GFNIKDTYIH (SEQ ID No. 1) CDR2 RIYPTNGY.sup.57TR.sup.59 YADSVKG (SEQ ID No. 2) CDR3 WGGDGFYAMDY (SEQ ID No. 3) For the light chain: CDR1 RASQDVN.sup.30TAVA (SEQ ID No. 4) CDR2 SASF.sup.53LYS (SEQ ID No. 5) CDR3 QQHY.sup.92TTPPT (SEQ ID No. 6). At least one of Y57, R59, N30, F53, and Y92 is substituted by an amino acid that confers on said antibody a reduced erbB2 binding affinity (Kd) that is in the range from 0.1 nM to 100 nM. The substitution is other than N30A, F53N, Y92A and Y92F when there is a single substitution in the antibody light chain.
Inventor(s):	Tikhomirov; Ilia Alexandre (Toronto, CA), Jaramillo; Maria L. (Beaconsfield, CA), O\'Connor-McCourt; Maureen D. (Beaconsfield, CA), Sulea; Traian (Kirkland, CA), Gilbert; Renald (Montreal, CA), Gaillet; Bruno (Sainte Julienne, CA), Baardsnes; Jason (Montreal, CA)
Assignee:	National Research Council of Canada (Ottawa, CA)
Application Number:	13/992,051
Patent Claims:	1. An antibody or a bivalent fragment thereof that binds preferentially to disease cells having an erbB2 density greater than a normal erbB2 density, the antibody comprising a heavy chain (HC) comprising a complementarity determining region (CDR)1 comprising the sequence GFNIKDTYIH (SEQ ID No. 1); a CDR2 comprising the sequence RIYPTNGY.sup.57TR.sup.59YADSVKG (SEQ ID No. 2); and a CDR3 comprising the sequence WGGDGFYAMDY (SEQ ID No. 3); and, a light chain (LC) comprising a CDR1 comprising the sequence RASQDVN.sup.30TAVA (SEQ ID No. 4); a CDR2 comprising the sequence SASF.sup.53LYS (SEQ ID No. 5); and a CDR3 comprising the sequence QQHY.sup.92TTPPT (SEQ ID No. 6), wherein the light chain contains substitutions consisting of LC F53N and LC Y92A. 2. An antibody or a bivalent fragment thereof that binds preferentially to disease cells having an erbB2 density greater than a normal erbB2 density, the antibody comprising a heavy chain (HC) comprising a complementarity determining region (CDR)1 comprising the sequence GFNIKDTYIH (SEQ ID No. 1); a CDR2 comprising the sequence RIYPTNGY.sup.57TR.sup.59YADSVKG (SEQ ID No. 2); and a CDR3 comprising the sequence WGGDGFYAMDY (SEQ ID No. 3); and, a light chain (LC) comprising a CDR1 comprising the sequence RASQDVN.sup.30TAVA (SEQ ID No. 4); a CDR2 comprising the sequence SASF.sup.53LYS (SEQ ID No. 5); and a CDR3 comprising the sequence QQHY.sup.92TTPPT (SEQ ID No. 6), wherein the light chain and heavy chain contain substitutions consisting of HC Y57A and LC N300. 3. An antibody according to claim 1, the antibody having the framework region sequences of trastuzumab. 4. An antibody according to claim 1, the antibody having the framework region sequences and the constant region sequence of trastuzumab. 5. A bivalent fragment of an antibody according to claim 1. 6. A conjugate comprising a cytotoxin or a detectable label and, conjugated thereto, an antibody or bivalent fragment thereof as defined according to claim 1. 7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an antibody in an amount useful to control the growth of cells presenting erbB2 at a density greater than the normal erbB2 density, in a subject in need thereof, wherein the antibody is an antibody or bivalent fragment thereof as defined according to claim 1. 8. An antibody according to claim 2, the antibody having the framework region sequences of trastuzumab. 9. An antibody according to claim 2, the antibody having the framework region sequences and the constant region sequence of trastuzumab. 10. A bivalent fragment of an antibody according to claim 2. 11. A conjugate comprising a cytotoxin or a detectable label and, conjugated thereto, an antibody or bivalent fragment thereof as defined according to claim 2. 12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an antibody in an amount useful to control the growth of cells presenting erbB2 at a density greater than the normal erbB2 density, in a subject in need thereof, wherein the antibody is an antibody or bivalent fragment thereof as defined according to claim 2.

Details for Patent 10,208,129

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2030-12-06
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2030-12-06
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2030-12-06