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1. WO2016146134 - ANTIBODIES TOWARDS AN EXTRACELLULAR REGION OF NBCN1

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[ EN ]

Claims

An antibody or antigen binding fragment thereof specifically recognizing and binding an extracellular polypeptide region of human NBCnl

The antibody or antigen binding fragment thereof according to claim 1 , wherein said extracellular polypeptide region comprises or consists of a sequence selected from any one of SEQ ID NO: 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15 or a fragment thereof.

The antibody or antigen binding fragment thereof according to claim 1 , wherein said extracellular polypeptide region comprises or consists of a sequence selected from SEQ ID NO: 14 and 15.

The antibody or antigen binding fragment thereof according to any of the preceding claims, wherein said antibody or antigen binding fragment thereof is capable of inhibiting cellular NBCnl-mediated Na+-dependent HC03" transport.

A method of selecting an antibody, said method comprising

a) Providing an antibody library,

b) Providing one or more antigens from an extracellular polypeptide region of human NBCnl ,

c) Contacting said antibody library with said one or more antigens, and d) Selecting antibodies, which bind said one or more antigens.

A method of producing an antibody specifically recognizing and binding an extracellular polypeptide region of human NBCnl , wherein said antibody is capable of inhibiting cellular NBCnl-mediated Na+-dependent HC03" transport, said method comprising the steps of administering to an animal, preferably a mammal, an extracellular polypeptide fragment of human NBCnl or a homolog at least 98% identical thereto, isolating antibodies from said mammal, testing whether antibodies are capable of inhibiting cellular NBCnl-mediated Na+- dependent HC03" transport and selecting antibodies capable of inhibiting cellular NBCnl-mediated Na+-dependent HC03" transport.

The method according to claim 6, wherein said extracellular polypeptide fragment is selected from the group consisting of SEQ ID NO: 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15and fragments thereof

8. An antibody obtainable by a method of any of claims 5-7.

9. An antibody as defined as defined in any of claims 1-4 and 8 for use in

medicine.

10. An antibody as defined as defined in any of claims 1-4 and 8 for use in the

treatment of breast cancer, atherosclerosis and/or restenosis.

1 1. The use according to claim 10, wherein said breast cancer is a triple negative breast cancer, an estrogen receptor-positive breast cancers or a HER2-positive breast cancer.

12. The use according to any of the preceding claims 10-11 , where said use is combined with at least one additional agent.

13. The use according to claim 12, where said at least one additional agent is an additional anti breast cancer agent, such as an estrogen-receptor antibody or a HER2 antibody, or a regulator of an ion channel transport, such as an Na+,H+- exchanger (NHE), a monocarboxylic acid transporter (MCT) or a proton pump inhibitor (PPI).

14. A method of treating breast cancer, atherosclerosis and/or restenosis

comprising administering a pharmaceutically acceptable amount of an antibody as defined in any of the preceding claims 1-4 and 8 to a subject in need thereof.

15. A method of inhibiting cellular NBCnl-mediated Na+-dependent HC03"

transport, said method comprising providing a sufficient amount of an antibody as defined in any of the preceding claims 1-4 and 8 to target cells.