Anti-OPG antibodies
The present invention relates to anti-OPG antibodies, and to methods of treatment, uses and pharmaceutical compositions comprising such antibodies, for example in the treatment and prevention of PAH.
1. An antibody or an antigen-binding fragment thereof that specifically binds to human osteoprotegerin (hOPG), and inhibits the interaction of hOPG with human receptor activator of NF K B ligand (hRANKL), comprising a heavy chain variable (V H ) region and a light chain variable (V L ) region, comprising:
(a) the CDRH1 amino acid sequence of SEQ ID NO: 46 or SEQ ID NO: 49, the CDRH2 amino acid sequence of SEQ ID NO: 47 or SEQ ID NO: 50, the CDRH3 sequence of SEQ ID NO: 48 or SEQ ID NO: 51; and
(b) the CDRL1 sequence of SEQ ID NO: 56 or SEQ ID NO: 59, the CDRL2 sequence of SEQ ID NO: 57 or SEQ ID NO: 60, and the CDRL3 sequence of SEQ ID NO: 58 or SEQ ID NO: 61.
2. The antibody or antigen-binding fragment thereof of claim 1 , comprising a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 117, SEQ ID NO: 118, or SEQ ID NO: 121.
3. The antibody or antigen-binding fragment thereof of claim 1 , comprising a light chain constant region comprising the amino acid sequence of SEQ ID NO: 123, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131, SEQ ID NO: 133, SEQ ID NO: 135, SEQ ID NO: 139, SEQ ID NO: 141, SEQ ID NO: 143, SEQ ID NO: 145, SEQ ID NO: 147, SEQ ID NO: 149, SEQ ID NO: 151, SEQ ID NO: 153, or SEQ ID NO: 163.
4. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
5. The pharmaceutical composition of claim 4 , further comprising a further therapeutic agent.
6. The pharmaceutical composition of claim 5 , wherein the further therapeutic agent is selected from the group consisting of calcium channel blockers, diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), endothelin receptor antagonists, prostacyclins, soluble guanalate cyclase agonists, phosphodiesterase inhibitors, alpha-adrenoceptor antagonists (α-blockers), beta-adrenoceptor antagonists (β-blockers), and dual α-, β-blockers.
7. A multispecific antibody or fusion protein comprising the antibody or antigen-binding fragment thereof of claim 1 .
8. An antibody or an antigen-binding fragment thereof that specifically binds to human osteoprotegerin (hOPG), and inhibits the interaction of hOPG with human receptor activator of NF K B ligand (hRANKL), comprising a heavy chain variable (V H ) region and a light chain variable (V L ) region, the antibody or antigen-binding fragment thereof comprising the V H region amino acid sequence of SEQ ID NO: 52 and the V L region amino acid sequence of SEQ ID NO: 62.
9. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 8 and a pharmaceutically acceptable carrier.
10. The pharmaceutical composition of claim 9 , further comprising a further therapeutic agent.
11. The pharmaceutical composition of claim 10 , wherein the further therapeutic agent is selected from the group consisting of calcium channel blockers, diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), endothelin receptor antagonists, prostacyclins, soluble guanalate cyclase agonists, phosphodiesterase inhibitors, alpha-adrenoceptor antagonists (α-blockers), beta-adrenoceptor antagonists (β-blockers), and dual α-, β-blockers.
12. A multispecific antibody or fusion protein comprising the antibody or antigen-binding fragment thereof of claim 8 .
13. An antibody that specifically binds to human osteoprotegerin (hOPG), and inhibits the interaction of hOPG with human receptor activator of NF K B ligand (hRANKL), the antibody or antigen-binding fragment thereof comprising a full-length heavy chain comprising the amino acid sequence of SEQ ID NO: 54 and a full-length light chain comprising the amino acid sequence of SEQ ID NO: 64.
14. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 13 and a pharmaceutically acceptable carrier.
15. The pharmaceutical composition of claim 14 , further comprising a further therapeutic agent.
16. The pharmaceutical composition of claim 15 , wherein the further therapeutic agent is selected from the group consisting of calcium channel blockers, diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), endothelin receptor antagonists, prostacyclins, soluble guanalate cyclase agonists, phosphodiesterase inhibitors, alpha-adrenoceptor antagonists (α-blockers), beta-adrenoceptor antagonists (β-blockers), and dual α-, β-blockers.
17. A multispecific antibody or fusion protein comprising the antibody of claim 13 .