Therapeutic molecules
The invention relates to binding molecules that bind specifically to prostate specific membrane antigen (PSMA), in particular, single human variable heavy chain domain antibodies and related methods for treatment of cancer.
1. A binding molecule capable of binding human PSMA comprising a single human variable heavy chain domain (V H ) antibody comprising CDR1, CDR2 and CDR3 sequences selected from
a CDR1 sequence comprising SEQ ID NO. 81, a CDR2 sequence comprising SEQ ID NO. 82 and a CDR3 sequence comprising SEQ ID NO. 83, or
a CDR1 sequence comprising SEQ ID NO. 85, a CDR2 sequence comprising SEQ ID NO. 86 and a CDR3 sequence comprising SEQ ID NO. 87, or
a CDR1 sequence comprising SEQ ID NO. 89, a CDR2 sequence comprising SEQ ID NO. 90 and a CDR3 sequence comprising SEQ ID NO. 91, or
a CDR1 sequence comprising SEQ ID NO. 125, a CDR2 sequence comprising SEQ ID NO. 126 and a CDR3 sequence comprising SEQ ID NO. 127, or
a CDR1 sequence comprising SEQ ID NO. 129, a CDR2 sequence comprising SEQ ID NO. 130 and a CDR3 sequence comprising SEQ ID NO. 131, or
a CDR1 sequence comprising SEQ ID NO. 133, a CDR2 sequence comprising SEQ ID NO. 134 and a CDR3 sequence comprising SEQ ID NO. 135, or
a CDR1 sequence comprising SEQ ID NO. 137, a CDR2 sequence comprising SEQ ID NO. 138 and a CDR3 sequence comprising SEQ ID NO. 139, or
a CDR1 sequence comprising SEQ ID NO. 145, a CDR2 sequence comprising SEQ ID NO. 146 and a CDR3 sequence comprising SEQ ID NO. 147, or
a CDR1 sequence comprising SEQ ID NO. 149, a CDR2 sequence comprising SEQ ID NO. 150 and a CDR3 sequence comprising SEQ ID NO. 151, or
a CDR1 sequence comprising SEQ ID NO. 165, a CDR2 sequence comprising SEQ ID NO. 166 and a CDR3 sequence comprising SEQ ID NO. 167.
2. The binding molecule according to claim 1 , wherein said V H domain comprises or consists of SEQ ID NO. 84, 88, 92, 128, 132, 136, 140, 148, 152, or 168.
3. The binding molecule according to claim 1 , wherein said binding molecule comprises two or more single V H domain antibodies wherein at least one of the single V H domain antibodies binds specifically to PSMA.
4. The binding molecule according to claim 1 wherein said binding molecule is conjugated to a toxin, enzyme, radioisotope or a chemical moiety.
5. The binding molecule according to claim 1 , obtained or obtainable from a mouse that does not produce any functional endogenous light or heavy chains.
6. The binding molecule according to claim 1 , conjugated to a moiety.
7. The binding molecule according to claim 6 , wherein said moiety is a toxin.
8. A pharmaceutical composition comprising the binding molecule according to claim 1 and a pharmaceutical carrier.
9. A method for treating prostate cancer or a prostate tumor comprising administering a therapeutically-effective amount of the binding molecule according to claim 1 .
10. A method for treating prostate cancer or a prostate tumor comprising administering a therapeutically-effective amount of the pharmaceutical composition according to claim 8 .