Compositions and methods for treating osteolytic disorders comprising MMP-14 binding proteins
View Patent ↗Provided are methods and compositions for using MMP-14 or MMP-9 binding proteins alone or in combination with other therapeutic agents to treat osteolytic disorders such as osteotropic cancer and osteoporosis.
1. A method for treating osteotropic cancer arising from a metastatic breast cancer in a subject, the method comprising administering to the subject an effective amount of an antibody that specifically binds to a MMP-14polypeptide comprising SEQ ID NO: 1, wherein the antibody inhibits the activity of MMP-14 and comprises a heavy chain immunoglobulin variable domain sequence and a light chain immunoglobulin variable domain, wherein the heavy chain immunoglobulin variable domain sequence comprises the heavy chain CDR1, CDR2 and CDR3 of SEQ ID NO:22 and the light chain immunoglobulin variable domain sequence comprises the CDR1, CDR2 and CDR3 of SEQ ID NO: 23, thereby treating the osteotropic cancer in the subject.
2. The method of claim 1 , further comprising administering an additional therapeutic to the subject.
3. The method of claim 2 , wherein the additional therapeutic is selected from the group consisting of an antitubulin/antimicrotubule agent, a topoisomerase I inhibitor, an antimetabolite, an alkylating agent, an apoptotic agent, and an anti-hormone.
4. The method of claim 2 , wherein the additional therapeutic is selected from the group consisting of: a bisphosphonate, a hormone-related compound, a RANKL antagonist, an α γ β3-antagonist, a Src inhibitor, a cathepsin K inhibitor and calcitonin.
5. A method for reducing the development of osteolytic lesions arising from a metastatic breast cancer in a subject, the method comprising administering to the subject an effective amount of an antibody that specifically binds to a MMP-14 polypeptide comprising SEQ ID NO: 1, wherein the antibody inhibits the activity of MMP-14 and comprises a heavy chain immunoglobulin variable domain sequence and a light chain immunoglobulin variable domain sequence, wherein the heavy chain immunoglobulin variable domain sequence comprises the heavy chain CDR1, CDR2 and CDR3 of SEQ ID NO:22 and the light chain immunoglobulin variable domain sequence comprises the CDR1, CDR2 and CDR3 of SEQ ID NO:23, thereby reducing the development of said osteolytic lesions in the subject.
6. The method of claim 5 , further comprising administering an additional therapeutic to the subject.
7. The method of claim 5 , wherein the additional therapeutic is selected from the group consisting of an antitubulin/antimicrotubule agent, a topoisomerase I inhibitor, an antimetabolite, an alkylating agent, an apoptotic agent, and an anti-hormone.
8. The method of claim 5 , wherein the additional therapeutic is selected from the group consisting of: a bisphosphonate, a hormone-related compound, a RANKL antagonist, an α γ β3-antagonist, a Src inhibitor, a cathepsin K inhibitor and calcitonin.
9. The method of claim 1 or 5 , wherein the antibody is an antibody fragment selected from the group consisting of a Fab fragment, a soluble Fab (sFab) fragment, an F(ab′) 2 fragment, an Fd fragment, and an Fv fragment.
10. The method of claim 1 or 5 , wherein the antibody comprises the heavy chain variable region comprising SEQ ID NO:22.
11. The method of claim 1 or 5 , wherein the antibody comprises the light chain variable region comprising SEQ ID NO:23.
12. The method of claim 1 or 5 , wherein the antibody comprises the heavy chain variable region comprising SEQ ID NO:22 and the light chain variable region comprising SEQ ID NO:23.
13. The method of claim 1 or 5 , wherein the antibody is an IgG1 antibody.
14. The method of claim 1 or 5 , wherein the antibody is a humanized antibody or a deimmunized antibody.
15. The method of claim 1 or 5 , wherein the antibody is PEGylated.
16. The method of claim 1 or 5 , wherein the antibody is a primate antibody or a chimeric antibody comprising a primate Fc domain.