Pharmaceutical compositions comprising an antibody which binds the human anti-Müllerian 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. Pharmaceutical composition comprising, as active ingredient, in combination with a pharmaceutically acceptable vehicle,
an anticancer agent chosen among olaparib, rucaparib and bevacizumab, and
a mutated humanized 12G4 monoclonal antibody binding the human anti-Müllerian hormone type II receptor (AMHR-II) comprising:
a) a light chain comprising:
a variable region the amino acid sequence of which is represented by SEQ ID NO: 7 or SEQ ID NO: 8,
a constant region the amino acid sequence of which is represented by SEQ ID NO: 3
b) a heavy chain comprising:
a variable region the amino acid sequence of which is represented by SEQ ID NO: 9 or SEQ ID NO: 10,
a constant region the amino acid sequence of which is represented by SEQ ID NO: 6.
2. Composition according to claim 1 , in which said antibody possesses affinity for AMHR-II characterized by a K D less than 10 −7 M.
3. Pharmaceutical composition according to claim 1 , in which the antibody is produced by the 3C23K.
4. Pharmaceutical composition according to claim 1 , in which said antibody is a recombinant antibody produced by animal transgenesis.
5. Pharmaceutical composition according to claim 1 , comprising the mutated 12G4 monoclonal antibody produced by the 3C23K clone, and olaparib.
6. Pharmaceutical composition according to claim 1 , comprising the mutated 12G4 monoclonal antibody produced by the 3C23K clone, and rucaparib.
7. Pharmaceutical composition according to claim 1 , in a formulation intended for administration by the intravenous or intraperitoneal route.
8. Pharmaceutical composition according to claim 1 , in which the therapeutically effective quantity of antibody administered to a patient is in a range from about 0.07 mg to about 35000 mg.
9. Pharmaceutical composition according to claim 1 , in which the therapeutically effective quantity of anticancer agent administered to a patient is in a range from about 10 mg to about 700 mg.
10. Pharmaceutical composition according to claim 1 , in which the dose of antibody administered to a patient is about 70 mg and the dose of anticancer agent administered to the patient is about 110 mg.
11. Pharmaceutical composition according to claim 1 , comprising the mutated 12G4 monoclonal antibody produced by the 3C23K clone, and bevacizumab.
12. Method for treating a pathology associated with the human anti-Müllerian hormone type II receptor (AMHR-II) comprising the administration of a therapeutically effective quantity of the composition comprising:
an anticancer agent chosen among olaparib, rucaparib and bevacizumab, 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,
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,
a constant region the amino acid sequence of which is represented by SEQ ID NO: 6.
13. The method of claim 12 wherein the quantity of the antibody administered to a patient is in a range from about 0.07 mg to about 35000 mg.
14. The method of claim 12 wherein the quantity of antibody administered is from 0.1 mg/kg to 100 mg/kg.
15. The method of claim 12 wherein the quantity of anticancer agent administered to a patient is in a range from about 20 mg to about 350 mg.
16. The method of claim 12 wherein the quantity of anticancer agent administered to a patient is about 110 mg.
17. Method for treating a pathology, according to claim 12 , in which the pathology associated with the human anti-Müllerian hormone type II receptor (AMHR-II) is cancer.
18. Method for treating a pathology according to claim 12 , in which the cancer is an ovarian cancer.
19. Method for treating a pathology according to claim 12 , in which the cancer is an endometrial cancer.
20. Method for treating a pathology according to claim 12 , in which the cancer is a mixed Müllerian malignant tumor of the uterus.