Neutralizing prolactin receptor antibody Mat3 and its therapeutic use
The present invention is directed to the neutralizing prolactin receptor antibody Mat3, and antigen binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation and for the treatment and prevention of antiestrogen-resistant breast cancer. The antibody of the invention blocks prolactin receptor-mediated signalling.
1. An isolated nucleic acid molecule comprising:
a nucleic acid sequence encoding an antibody Mat3 or an antigen-binding fragment thereof which antagonizes prolactin receptor (PRLR)-mediated signaling,
wherein:
a variable heavy chain comprises the sequences of CDR1, CDR2, and CDR3 corresponding to SEQ ID NO: 5, 6, and 7, respectively,
a variable light chain comprises the sequences of CDR1, CDR2, and CDR3 corresponding to SEQ ID NO: 8, 9, and 10, respectively,
the antibody or antigen-binding fragment thereof comprises an antigen-binding region that binds specifically to one or more regions of the extracellular domain of PRLR, and
the PRLR is depicted by the amino acid sequence from position 1 to 210 of SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13.
2. An isolated nucleic acid sequence according to claim 1 , wherein the nucleic acid molecule comprises the nucleic acid sequence of SEQ ID NO: 3 and the nucleic acid sequence of SEQ ID NO: 4.
3. An expression vector comprising the nucleic acid molecule of claim 1 .
4. A host cell comprising the vector of claim 3 , whereby the host cell is a eukaryotic cell or a prokaryotic cell.