Claims for Patent: 9,821,074

Summary for Patent: 9,821,074

Title:	Pyrrolobenzodiazepines and conjugates thereof
Abstract:	Conjugate compounds of formula (A): ##STR00001## wherein: R.sup.2 is ##STR00002## where R.sup.36a and R.sup.36b are independently selected from H, F, C.sub.1-4 saturated alkyl, C.sub.2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C.sub.1-4 alkyl amido and C.sub.1-4 alkyl ester or, when one of R.sup.36a and R.sup.36b is H, the other is selected from nitrile and a C.sub.1-4 alkyl ester; R.sup.6 and R.sup.9 are independently selected from H, R, OH, OR, SH, SR, NH.sub.2, NHR, NRR\', NO.sub.2, Me.sub.3Sn and halo; R.sup.7 is independently selected from H, R, OH, OR, SH, SR, NH.sub.2, NHR, NRR\', NO.sub.2, Me.sub.3Sn and halo; Y is selected from formulae A1, A2, A3, A4, A5 and A6: ##STR00003## ##STR00004## L is a linker connected to a cell binding agent; CBA is the cell binding agent; n is an integer selected in the range of 0 to 48; R.sup.A4 is a C.sub.1-6 alkylene group; either (a) R.sup.10 is H, and R.sup.11 is OH, OR.sup.A, where R.sup.A is C.sub.1-4 alkyl; or (b) R.sup.10 and R.sup.11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R.sup.10 is H and R.sup.11 is OSO.sub.zM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; R and R\' are each independently selected from optionally substituted C.sub.1-12 alkyl, C.sub.3-20 heterocyclyl and C.sub.5-20 aryl groups, and optionally in relation to the group NRR\', R and R\' together with the nitrogen atom to which they are attached form an optionally substituted 4-, 5-, 6- or 7-membered heterocyclic ring; wherein R.sup.16, R.sup.17, R.sup.19, R.sup.20, R.sup.21 and R.sup.22 are as defined for R.sup.6, R.sup.7, R.sup.9, R.sup.10, R.sup.11 and R.sup.2 respectively; wherein Z is CH or N; wherein T and T\' are independently selected from a single bond or a C.sub.1-9 alkylene, which chain may be interrupted by one or more heteroatoms e.g. O, S, N(H), NMe, provided that the number of atoms in the shortest chain of atoms between X and X\' is 3 to 12 atoms; and X and X\' are independently selected from O, S and N(H).
Inventor(s):	Howard; Philip Wilson (London, GB), Flygare; John A. (South San Francisco, CA), Pillow; Thomas (South San Francisco, CA), Wei; Binqing (South San Francisco, CA)
Assignee:	Genentech, Inc. (San Francisco, CA) MedImmue Limited (GB)
Application Number:	14/208,374
Patent Claims:	1. An antibody-drug conjugate compound comprising an antibody attached to one or more PBD drug moieties, and prepared by reacting the antibody and a PBD compound selected from: ##STR00090## ##STR00091## ##STR00092## wherein the antibody binds to one or more tumor-associated antigens or cell-surface receptors selected from: (4) 0772P (CA125, MUC16); (6) Napi3b (NAPI-3B, Napi2b, NPTIIb, SLC34A2, solute carrier family 34 (sodium phosphate), member 2, type II sodium-dependent phosphate transporter 3b); (17) HER2; (27) CD22 (B-cell receptor CD22-B isoform); (37) CD33 (CD33 molecule, SIGLEC-3, SIGLEC3, p67; CD33 antigen (gp67); gp67; myeloid cell surface antigen CD33; sialic acid binding Ig-like lectin 3; sialic acid-binding Ig-like lectin); and (38) LGR5/GPR49. 2. The antibody-drug conjugate compound of claim 1 wherein the antibody is a cysteine-engineered antibody. 3. The antibody-drug conjugate compound of claim 2 wherein the antibody is an antibody which binds to an ErbB receptor. 4. The antibody-drug conjugate compound of claim 3 wherein the antibody is trastuzumab. 5. The antibody-drug conjugate compound of claim 1 wherein the antibody is selected from an anti-HER2 antibody, an anti-CD33 antibody, an anti-LGR5 antibody, an anti-Napi3b antibody, an anti-MUC16 antibody, and an anti-CD22 antibody. 6. The antibody-drug conjugate compound according to claim 1 comprising a mixture of the antibody-drug conjugate compounds, wherein the average drug loading per antibody in the mixture of antibody-drug conjugate compounds is about 2 to about 5. 7. A pharmaceutical composition comprising the antibody-drug conjugate compound of claim 1, and a pharmaceutically acceptable diluent, carrier or excipient. 8. A method of treating a patient with cancer, comprising administering an effective amount of the pharmaceutical composition according to claim 7 to the patient.

Details for Patent 9,821,074

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2039-02-26
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2039-02-26
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2039-02-26