Angiogenesis inhibiting molecules, their selection, production and their use in the treatment of cancer
View Patent ↗The present invention relates to a method for providing molecules that are capable of inhibiting angiogenesis, comprising the steps of providing a range of molecules; testing whether these molecules can prevent interaction between JAM-B and JAM-C; testing the positive molecules for their ability to block angiogenesis in vivo; and selecting molecules that are positive in the angiogenesis test as angiogenesis inhibiting molecules. The method may further comprise the step of isolating or producing the angiogenesis inhibiting molecules. The invention further relates to the angiogenesis inhibiting molecules thus provided and produced, to their use in the treatment of cancer, to therapeutical compositions comprising them. In a particular embodiment the invention relates to monoclonal antibodies, in particular MAb H33, to soluble JAM-C and JAM-B and to small molecules.
1. A hybridoma cell line 13H33 as deposited with the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH under the deposit accession number DSM ACC2622.
2. An isolated antibody selected from: a) monoclonal antibody H33, produced by hybridoma 13H33 as deposited with the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH under the deposit accession number DSM ACC2622, b) isolated antigen binding fragments of the antibody H33, or c) a recombinant antibody that has a binding specificity identical to the H33 antibody and comprises all of the CDRs of the H33 antibody.
3. The isolated antibody according to claim 2 , wherein said isolated antibody is the monoclonal antibody H33, produced by hybridoma 13H33 as deposited with the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH under the deposit accession number DSM ACC2622.
4. The isolated antibody according to claim 2 , wherein said isolated antibody is an isolated antigen binding fragment of the antibody H33.
5. The isolated antibody according to claim 2 , wherein said isolated antibody is a recombinant antibody having a binding specificity identical to the H33 antibody and comprising all of the CDRs of the H33 antibody.
6. The isolated antibody according to claim 2 , wherein the recombinant antibody or the isolated antigen binding fragments of the antibody H33 is:
a) a Fab fragment;
b) a Fv fragment comprising all of the CDRs of the heavy and light chains of the H33 antibody; or
c) a scFv, a dimer of a scFv, a trimer of a scFv or a larger aggregate of a scFv, at least one of said scFv comprising all of the CDRs of the H33 antibody and having a binding specificity identical to the H33 antibody.
7. The isolated antibody according to claim 6 , wherein the isolated antigen binding fragments of the antibody H33 are Fab fragments.
8. The isolated antibody according to claim 6 , wherein the recombinant antibody is a Fv fragment and comprises all of the CDRs of the H33 antibody.
9. The isolated antibody according to claim 6 , wherein the recombinant antibody is a scFv, a dimer of a scFv, a trimer of a scFv or a larger aggregate of a scFv, at least one of said scFv comprising all of the CDRs of the H33 antibody and having a binding specificity identical to the H33 antibody.
10. The isolated antibody according to claim 2 , wherein the recombinant antibody is:
a) a humanized antibody comprising all of the CDRs of the H33 antibody; or
b) a chimeric antibody having a binding specificity identical to H33 and comprising all of the CDRs of the H33 antibody.
11. The isolated antibody according to claim 10 , wherein the recombinant antibody is a humanized antibody and comprises all of the CDRs of the H33 antibody.
12. The isolated antibody according to claim 10 , wherein the recombinant antibody is a chimeric antibody and comprises all of the CDRs of the H33 antibody.
13. A recombinant antibody comprising:
a) a V HH comprising all of the heavy chain CDRs of the H33 antibody produced by hybridoma 13H33 deposited as DSM ACC2622; or
b) a single domain antigen binding fragment comprising all of the heavy chain CDRs of the H33 antibody.
14. The recombinant antibody according to claim 13 , wherein said recombinant antibody comprises a single domain antigen binding fragment comprising all of the heavy chain CDRs of the H33 antibody.
15. The recombinant antibody according to claim 13 , wherein said recombinant antibody comprises a V HH comprising all of the heavy chain CDRs of the H33 antibody.
16. A composition comprising a carrier and an antibody selected from: a) monoclonal antibody H33, produced by hybridoma 13H33 as deposited with the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH under the deposit accession number DSM ACC2622, b) isolated antigen binding fragments of the antibody H33, or c) a recombinant antibody having a binding specificity identical to the H33 antibody and comprising all of the CDRs of the H33 antibody.
17. The composition according to claim 16 , wherein the antibody is the monoclonal antibody H33, produced by hybridoma 13H33 as deposited with the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH under the deposit accession number DSM ACC2622.
18. The composition according to claim 16 , wherein the antibody is an antigen binding fragment of the antibody H33.
19. The composition according to claim 16 , wherein the antibody is a recombinant antibody having a binding specificity identical to the H33 antibody and comprising all of the CDRs of the H33 antibody.
20. The composition according to claim 16 , wherein the antibody is a recombinant antibody or isolated antigen binding fragments of the antibody H33 and:
a) are Fab fragments;
b) is a Fv fragment comprising all of the CDRs of the H33 antibody; or
c) is a scFv, a dimer of a scFv, a truer of a scFv or a larger aggregate of a scFv, at least one of said scFv comprising all of the CDRs of the H33 antibody and having a binding specificity identical to the H33 antibody.
21. The composition according to claim 20 , wherein the isolated antigen binding fragments of the antibody H33 are Fab fragments.
22. The composition according to claim 20 , wherein the recombinant antibody is a Fv fragment that comprises all of the CDRs of the H33 antibody.
23. The composition according to claim 20 , wherein the recombinant antibody is a scFv, a dimer of a scFv, a trimer of a scFv or a larger aggregate of a scFv, at least one of said scFv comprising all of the CDRs of the H33 antibody and having a binding specificity identical to the H33 antibody.
24. The composition according to claim 16 , wherein the recombinant antibody is:
a) a humanized antibody comprising all of the CDRs of the H33 antibody; or
b) a chimeric antibody having a binding specificity identical to H33 and comprising all of the CDRs of the H33 antibody.
25. The composition according to claim 24 , wherein the recombinant antibody is a humanized antibody that comprises all of the CDRs of the H33 antibody.
26. The composition according to claim 24 , wherein the recombinant antibody is a chimeric antibody that comprises all of the CDRs of the H33 antibody.