ANTI-PSMA CONJUGATES

1 . An antibody drug conjugate of formula Ab-L-D where Ab is an antibody that binds to prostate-specific membrane antigen (PSMA), conjugated to a DNA-binding cytotoxin comprising a pyrrolobenzodiazepine (PBD) dimer, wherein the antibody comprises (i) an immunoglobulin heavy chain variable region having a CDR1 region with the amino acid sequence shown in SEQ ID NO: 3, a CDR2 region with the amino acid sequence shown in SEQ ID NO: 4, and a CDR3 region with the amino acid sequence shown in SEQ ID NO: 5; and (ii) an immunoglobulin light chain variable region having a CDR1 region with the amino acid sequence shown in SEQ ID NO: 6, a CDR2 region with the amino acid sequence shown in SEQ ID NO: 7, and a CDR3 region with the amino acid sequence shown in SEQ ID NO: 8;

and L-D is a drug linker of formula (III)

wherein:

(a) R LL is a linker for connection to the antibody;

(b) (i) R 10 and R 11 together form a double bond between the nitrogen and carbon atoms to which they are attached; (ii) R 10 is a linker R LLA for connection to the antibody and R 11 is OH; or (iii) R 10 is a capping group R C and R 11 is OH; and

(c) m is 0 or 1;

with the proviso that an antibody drug conjugate comprising either of the following drug linkers is specifically excluded:

2 . The conjugate according to claim 1 wherein the antibody comprises an immunoglobulin heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 1.

3 . The conjugate according to claim 1 wherein the antibody comprises an immunoglobulin light chain variable region having the amino acid sequence shown in SEQ ID NO: 2.

4 . The conjugate according to claim 1 wherein m=0.

5 . The conjugate according to claim 1 wherein R 10 and R 11 together form a double bond between the nitrogen and carbon atoms to which they are attached.

6 . The conjugate according to claim 1 wherein the conjugate comprises a linker of formula (IIa) between the cytotoxin and the antibody

wherein:

Q is:

where Q X is such that Q is an amino-acid residue, a dipeptide residue, a tripeptide residue or a tetrapeptide residue;

X, which is linked to G LL , is:

where a=0 to 5, b1=0 to 16, b2=0 to 16, c1=0 or 1, c2=0 or 1, d=0 to 5, wherein at least b1 or b2=0 and at least c1 or c2=0; and

G LL is a linker group connected to the antibody.

7 . The conjugate according to claim 1 wherein the conjugate comprises a cleavable linker between the cytotoxin and the antibody.

8 . The conjugate according to claim 6 wherein c2=1 and b1 is from 2 to 8.

9 . (canceled)

10 . The conjugate according to claim 1 where the cytotoxin is conjugated to the antibody at an endogenous and/or engineered N-linked glycosylation site.

11 . (canceled)

12 . A method of treating an individual suffering from prostate cancer which method comprises administering to the patient an antibody drug conjugate according to claim 1 .

13 . The conjugate according to claim 1 wherein the drug linker (L-D) is:

14 . The conjugate according to claim 1 wherein the drug linker (L-D) is attached to the antibody (Ab) at an N-linked glycosylation site at Asn-297.

15 . The conjugate according to claim 14 wherein the drug linker (L-D) is attached to the antibody (Ab) at an N-linked glycosylation site at Asn-297 through a trimmed Asn-GlcNAc residue.

16 . The conjugate according to claim 15 wherein the N-linked glycosylation site is Asn-297-GlcNAc-GalNAc.

17 . The conjugate according to claim 9 wherein the drug linker (L-D) is attached to the antibody (Ab) at an N-linked glycosylation site at Asn-297.

18 . The conjugate according to claim 17 wherein the drug linker (L-D) is attached to the antibody (Ab) at an N-linked glycosylation site at Asn-297 through a trimmed Asn-GlcNAc residue.

19 . The conjugate according to claim 18 wherein the N-linked glycosylation site is Asn-297-GlcNAc-GalNAc.

20 . The conjugate according to claim 7 wherein the cleavable linker is a cathepsin cleavable sequence.

21 . The conjugate according to claim 20 , wherein the cathepsin cleavable sequence is Val-Ala or Val-Cit.