H1.0k180me2 antibodies, methods of making and uses thereof

Abstract

Provided herein are antibodies that specifically bind a protein comprising an H1.0K180me2 antigen or a peptide thereof, methods of making such antibodies, and methods of using such antibodies for therapeutics and diagnostics.

1 - 52 . (canceled) 
     
     
         53 . An antibody or antigen-binding fragment thereof that specifically binds a protein comprising an H1.0K180me2 antigen or a peptide thereof, wherein the antigen-binding domain of the antibody comprises:
 (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 12 or SEQ ID NO: 13;   (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 16 or SEQ ID NO: 17;   (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 19;   (d) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26 or SEQ ID NO: 27; and   (d) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 or SEQ ID NO: 35.   
     
     
         54 . An antibody or antigen-binding fragment thereof that specifically binds a protein comprising an H1.0K180me2 antigen or a peptide thereof, wherein the heavy chain variable domain of the antibody or antigen-binding fragment thereof comprises at least 85% of the amino acid sequence of SEQ ID NO: 7 and the light chain variable domain of the antibody or antigen-binding fragment thereof comprises at least 85% the amino acid sequence of SEQ ID NO: 9. 
     
     
         55 . The antibody or antigen-binding fragment thereof of  claim 54 , wherein the heavy chain variable domain of the antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 7 and the light chain variable domain of the antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 9. 
     
     
         56 . The antibody or antigen-binding fragment thereof of  claim 53 , wherein the antibody is chimeric or humanized. 
     
     
         57 . The antibody or antigen-binding fragment thereof of  claim 53 , wherein the antibody is a monoclonal antibody. 
     
     
         58 . The antibody or antigen-binding fragment thereof of  claim 53 , wherein the antibody or antigen-binding fragment thereof does not bind, or only minimally binds, if the H1.0K180me2 protein or peptide comprises methylated lysine residues at lysine residues corresponding to K166, K172, K174, K175, and/or K177 of a human histone H1.0 protein. 
     
     
         59 . The antibody or antigen-binding fragment thereof of  claim 53 , wherein the antibody or antigen-binding fragment thereof is conjugated to a label. 
     
     
         60 . The antibody or antigen-binding fragment thereof of  claim 53 , wherein the antibody or antigen-binding fragment thereof is attached to a solid surface. 
     
     
         61 . The antibody of  claim 60 , wherein the antibody or antigen-binding fragment thereof is attached to a bead, column, resin, or a microplate. 
     
     
         62 . The antibody or antigen-binding fragment thereof of  claim 53 , wherein the antibody or antigen-binding fragment thereof is conjugated to an agent. 
     
     
         63 . The antibody or antigen-binding fragment thereof of  claim 62 , wherein the agent is selected from the group consisting of a radionuclide, a cytotoxin, a chemotherapeutic agent, a drug, a pro-drug, a toxin, an enzyme, an immunomodulator, a pro-apoptotic agent, a cytokine, a hormone, an oligonucleotide, an antisense molecule, a siRNA, and a second antibody. 
     
     
         64 . The antibody or antigen-binding fragment thereof of  claim 53 , wherein the heavy chain variable domain of the antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 7. 
     
     
         65 . A pharmaceutical composition comprising the antibody or antibody-binding fragment thereof of  claim 53 , and a pharmaceutically acceptable excipient. 
     
     
         66 . A kit comprising a therapeutically effective amount of the antibody or antibody-binding fragment thereof of  claim 53 . 
     
     
         67 . The article of manufacture of  claim 66 , wherein the article of manufacture is a transdermal patch or a transdermal microneedle array patch.