Molecules and methods for inhibiting shedding of KIM-1
View Patent ↗Disclosed are antibodies that inhibit proteolytic release of a soluble KIM-1 polypeptide from KIM-1 expressing cells. Also disclosed are methods of using the antibodies to inhibit shedding of the KIM-1 polypeptide.
1. An isolated antibody or antigen-binding fragment thereof that binds to an epitope within the amino acid sequence: SSDGLWNNNQTQLFLEHS (SEQ ID NO: 1).
2. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a humanized antibody.
3. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a fully human antibody.
4. A conjugate comprising the isolated antibody or antigen-binding fragment thereof of claim 1 linked to a detectable label.
5. A conjugate or fusion polypeptide comprising the isolated antibody or antigen-binding fragment thereof of claim 1 and a toxin moiety.
6. A composition comprising the isolated antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
7. An isolated cell that produces the antibody or antigen-binding fragment thereof of claim 1 .
8. The cell of claim 7 , wherein the cell is a mammalian cell.
9. The cell of claim 7 , wherein the cell is a hybridoma cell.
10. A method for making a hybrid cell that produces an antibody or antigen-binding-fragment thereof, the method comprising:
introducing into a first cell an expression vector comprising a nucleic acid sequence encoding a heavy chain of the antibody or antigen-binding-fragment thereof of claim 1 ;
introducing into a second cell an expression vector comprising a nucleic acid sequence encoding a light chain of the antibody or antigen-binding-fragment thereof of claim 1 ; and
fusing the first cell and the second cell to form a hybrid cell,
wherein the hybrid cell produces the antibody or antigen-binding-fragment thereof of claim 1 .
11. A method for producing an antibody or antigen-binding fragment thereof, the method comprising culturing the cell of claim 7 under conditions that allow production of the antibody or antigen-binding-fragment thereof by the cell.
12. The method of claim 11 , further comprising, after culturing the cell, isolating the antibody or antigen-binding-fragment thereof from the cell or culture medium in which the cell is cultured.
13. A method for producing an antibody or antigen-binging fragment thereof, the method comprising culturing a hybrid cell produced by the method of claim 10 under conditions that allow production of the antibody or antigen-binding-fragment thereof by the cell.
14. An isolated monoclonal antibody or antigen-binding-fragment thereof that binds to the extracellular domain of the human KIM-1 polypeptide of SEQ ID NO:7 and inhibits proteolytic release of a soluble KIM-1 polypeptide from a KIM-1-expressing cell.
15. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a single chain antibody.
16. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is a polyclonal antibody, a chimeric antibody, an F ab , fragment, an F (ab′)2 fragment, an F ab ′ fragment, an F sc fragment, or an F v fragment.
17. The isolated antibody or antigen-binding fragment thereof of claim 14 , wherein the antibody is a humanized antibody.
18. The isolated antibody or antigen-binding fragment thereof of claim 14 , wherein the antibody is a fully human antibody.
19. The isolated antibody or antigen-binding fragment thereof of claim 14 , wherein the antibody is a single chain antibody.
20. The isolated antibody or antigen-binding fragment thereof of claim 14 , wherein the antibody or antigen-binding fragment thereof is a chimeric antibody, an F ab fragment, an F (ab′)2 fragment, an F ab ′ fragment, an F sc fragment, or an F v fragment.