Pharmaceutical compositions comprising an antibody which binds the human anti-mullerian hormone receptor type II
The invention relates to novel pharmaceutical compositions including, as active ingredient, an antibody binding the human anti-Müllerian hormone type II receptor (AMHR-II) and an anticancer agent, as well as the therapeutic applications of these compositions.
1. A pharmaceutical composition comprising:
as active ingredient:
an anticancer agent selected from the group consisting of carboplatin, paclitaxel, doxorubicin, pegylated liposomal doxorubicin, and mixtures thereof, and
a mutated humanized 12G4 monoclonal antibody binding the human anti-Müllerian hormone type II receptor (AMHR-II) comprising or constituted by:
a) a light chain comprising or constituted by:
a variable region the amino acid sequence of which is represented by SEQ ID NO: 7 or SEQ ID NO: 8, and
a constant region the amino acid sequence of which is represented by SEQ ID NO: 3
b) a heavy chain comprising or constituted by:
a variable region the amino acid sequence of which is represented by SEQ ID NO: 9 or SEQ ID NO: 10, and
a constant region the amino acid sequence of which is represented by SEQ ID NO: 6; and
a pharmaceutically acceptable vehicle.
2. The pharmaceutical composition according to claim 1 , wherein said antibody possesses affinity for AMHR-II characterized by a K D of less than 10 −7 M.
3. The pharmaceutical composition according to claim 2 , wherein said antibody possesses affinity for AMHR-II characterized by a K D of less than 10 −8 M.
4. The pharmaceutical composition according to claim 2 , wherein said antibody possesses affinity for AMHR-II characterized by a K D in the range from 10 −9 M to 10 −11 M.
5. The pharmaceutical composition according to claim 1 , wherein said antibody is produced by a 3C23K clone.
6. The pharmaceutical composition according to claim 5 , comprising the mutated 12G4 monoclonal antibody produced by the 3C23K clone, and carboplatin.
7. The pharmaceutical composition according to claim 5 , comprising the mutated 12G4 monoclonal antibody produced by the 3C23K clone, and paclitaxel.
8. The pharmaceutical composition according to claim 1 , wherein said antibody is a recombinant antibody produced by animal transgenesis.
9. The pharmaceutical composition according to claim 1 , in a formulation intended for administration by the intravenous or intraperitoneal route.
10. The pharmaceutical composition according to claim 1 , wherein a therapeutically effective quantity of antibody administered to a patient is in a range from about 0.07 mg to about 35000 mg.
11. The pharmaceutical composition according to claim 10 , wherein the therapeutically effective quantity of antibody administered to a patient is in a range from about 0.7 mg to about 7000 mg.
12. The pharmaceutical composition according to claim 10 , wherein the therapeutically effective quantity of antibody administered to a patient is in a range from about 0.7 mg to about 1400 mg.
13. The pharmaceutical composition according to claim 10 , wherein the therapeutically effective quantity of antibody administered to a patient is in a range from about 0.7 mg to about 700 mg.
14. The pharmaceutical composition according to claim 10 , wherein the therapeutically effective quantity of antibody administered to a patient is in a range from about 0.7 mg to about 70 mg.
15. The pharmaceutical composition according to claim 1 , wherein a therapeutically effective quantity of anticancer agent administered to a patient is in a range from about 10 mg to about 700 mg.
16. The pharmaceutical composition according to claim 15 , wherein the therapeutically effective quantity of anticancer agent administered to a patient is in a range from about 20 mg to about 350 mg.
17. The pharmaceutical composition according to claim 15 , wherein the therapeutically effective quantity of anticancer agent administered to a patient is about 110 mg.
18. The pharmaceutical composition according to claim 1 , wherein a dose of antibody administered to a patient is about 70 mg and a dose of anticancer agent administered to the patient is about 110 mg.
19. The pharmaceutical composition according to claim 1 , wherein a therapeutically effective quantity of antibody is from 0.1 mg/kg to 100 mg/kg.
20. Composition A method for preventing or treating a pathology associated with human anti-Müllerian hormone type II receptor (AMHR-II) comprising administering to a subject in need thereof a composition comprising:
an anticancer agent selected from the group consisting of carboplatin, paclitaxel, doxorubicin, pegylated liposomal doxorubicin, and mixtures thereof, and
a mutated humanized 12G4 monoclonal antibody binding the human anti-Müllerian hormone type II receptor (AMHR-II)comprising or constituted by:
a) a light chain comprising or constituted by:
a variable region the amino acid sequence of which is represented by SEQ ID NO: 7 or SEQ ID NO: 8, and
a constant region the amino acid sequence of which is represented by SEQ ID NO: 3
b) a heavy chain comprising or constituted by:
a variable region the amino acid sequence of which is represented by SEQ ID NO: 9 or SEQ ID NO: 10, and
a constant region the amino acid sequence of which is represented by SEQ ID NO: 6.
21. The method according to claim 20 , wherein the pathology associated with the human anti-Müllerian hormone type II receptor (AMHR-II) is cancer.
22. The method according to claim 21 , wherein the cancer is an ovarian cancer.
23. The method according to claim 21 , wherein the cancer is an endometrial cancer.
24. The method according to claim 21 , wherein the cancer is a mixed Müllerian malignant tumor of the uterus.