Anti-GCC antibody molecules and related compositions and methods
Antibodies and antigen-binding fragments of antibodies that bind GCC are disclosed. The antibodies bind an extracellular domain of GCC and can be internalized. In some embodiments, the antibodies are humanized, chimeric or human. Nucleic acids and vectors encoding the antibodies or portions thereof, recombinant cells that contain the nucleic acids, and compositions comprising the antibodies or antigen-binding fragments are also disclosed. The invention also provides therapeutic and diagnostic methods utilizing the antibodies and antigen-binding fragments provided herein.
1. An anti-guanylyl cyclase C (GCC) antibody molecule comprising:
three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) comprising amino acid sequences of SEQ ID NO: 190 (HCDR1), SEQ ID NO: 192 (HCDR2), and SEQ ID NO: 194 (HCDR3); and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) comprising amino acid sequences of SEQ ID NO: 196 (LCDR1), SEQ ID NO: 198 (LCDR2), and SEQ ID NO: 200 (LCDR3).
2. The anti-GCC antibody molecule of claim 1 , wherein the anti-GCC antibody molecule comprises human or human derived heavy and light chain variable region frameworks.
3. The anti-GCC antibody molecule of claim 1 , wherein the anti-GCC antibody molecule comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 46; and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 48.
4. The anti-GCC antibody molecule of claim 1 , wherein the anti-GCC antibody molecule comprises a human IgG1 heavy chain constant region.
5. The anti-GCC antibody molecule of claim 1 , wherein the anti-GCC antibody molecule comprises a human Ig kappa light chain constant region.
6. The anti-GCC antibody molecule of claim 1 , wherein the anti-GCC antibody molecule is conjugated to a therapeutic agent or a detectable label.
7. An immunoconjugate of formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
Ab is the anti-GCC antibody molecule of claim 1 ;
X is a linker moiety which connects Ab and Z;
Z is a therapeutic agent or a detectable label; and
m is an integer from 1 to 15.
8. The immunoconjugate of claim 7 , wherein the therapeutic agent is a cytostatic or cytotoxic agent.
9. A pharmaceutical composition comprising the anti-GCC antibody molecule of claim 1 and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising the immunoconjugate of claim 7 and a pharmaceutically acceptable carrier.
11. A container comprising the pharmaceutical composition of claim 9 .
12. A kit comprising the anti-GCC antibody molecule of claim 1 .