US2014249298A1PendingUtilityA1

ANTI-HUMAN EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1 (hENT1) ANTIBODIES ADN METHODS OF USE THEREOF

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Assignee: UNIV ALBERTAPriority: Jun 16, 2010Filed: May 13, 2014Published: Sep 4, 2014
Est. expiryJun 16, 2030(~3.9 yrs left)· nominal 20-yr term from priority
Inventors:Marit Liland SandvoldFinn MyhrenCarol E. CassJames D. Young
C07K 2317/34G01N 33/68C07K 16/18A61P 35/00A61P 31/12C07K 16/28
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Claims

Abstract

This invention provides monoclonal antibodies that recognize hENT1. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and/or prophylactic in disorders associated with aberrant hENT1 expression and/or activity.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . An isolated monoclonal anti-human Equilibrative Nucleoside Transporter 1 (hENT1) antibody or antigen-binding fragment thereof, wherein said antibody comprises:
 (a) a variable heavy chain complementarity determining region 1 (VH CDR1) sequence comprising the amino acid sequence GYTFTDYE (SEQ ID NO: 10);   (b) a variable heavy chain complementarity determining region 2 (VH CDR2) sequence comprising the amino acid sequence IDPETGAI (SEQ ID NO: 11) or the amino acid sequence IDPETGKT (SEQ ID NO: 40); and   (c) a variable heavy chain complementarity determining region 3 (VH CDR3) sequence comprising the amino acid sequence TREFTY (SEQ ID NO: 12) or the amino acid sequence TRELTY (SEQ ID NO: 41); and   (d) a variable light chain complementarity determining region 1 (VL CDR1) sequence comprising the amino acid sequence QSLLFSNGKTY (SEQ ID NO: 24);   (e) a variable light chain complementarity determining region 2 (VL CDR2) sequence comprising the amino acid sequence LVS (SEQ ID NO: 25); and   (f) a variable light chain complementarity determining region 3 (VL CDR3) sequence comprising the amino acid sequence VQGTHFPWT (SEQ ID NO: 26),   wherein said antibody or antigen-binding fragment thereof binds hENT1 or a biologically active fragment thereof.   
     
     
         2 . The antibody of  claim 1 , wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable sequence comprising an amino acid sequence selected from SEQ ID NO: 2, 4, 6, 8, 9, 28, 30, 32, 34, 36, 38, 39, 51 and 53, and a light chain variable sequence comprising the amino acid sequence selected from SEQ ID NO: 14, 16, 18, 20, 22, 23, 43, 45, 47 and 49. 
     
     
         3 . The antibody of  claim 1 , wherein said antibody is an IgG isotype or antigen-binding fragment of an IgG isotype antibody. 
     
     
         4 . The antibody of  claim 3 , wherein said antibody is an IgG1 isotype or antigen-binding fragment of an IgG1 isotype antibody. 
     
     
         5 . The antibody of  claim 4 , wherein said antibody is an IgG1 kappa isotype or antigen-binding fragment of an IgG1 kappa isotype antibody. 
     
     
         6 . An isolated monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 2, 4, 6, 8, 9, 28, 30, 32, 34, 36, 38, 39, 51 or 53 and a light chain variable sequence comprising the amino acid sequence of SEQ ID NO: 14, 16, 18, 20, 22, 23, 43, 45, 47 or 49, wherein said antibody or antigen-binding fragment thereof binds human Equilibrative Nucleoside Transporter 1 (hENT1) or a biologically active fragment thereof. 
     
     
         7 . The antibody of  claim 6 , wherein said antibody is an IgG isotype or antigen-binding fragment of an IgG isotype antibody. 
     
     
         8 . A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of  claim 1  and a carrier. 
     
     
         9 . Use of the antibody of  claim 1  to detect a level of human Equilibrative Nucleoside Transporter 1 (hENT1) expression or activity in a subject or patient sample. 
     
     
         10 . The use of  claim 9 , wherein the detected level of hENT1 expression or activity in the subject or patient sample is used to identify a course of treatment for the subject. 
     
     
         11 . The use of  claim 10 , wherein the course of treatment is administration of gemcitabine, gemcitabine-5′-elaidic acid ester, gemcitabine-N4-elaidic acid amide, cytarabine, cytarabine-5′-elaidic acid ester, ribavirin-5′-elaidic acid ester, 5-azacytidine-5′-elaidic acid ester and combinations thereof. 
     
     
         12 . The use of  claim 9 , wherein the detected level of hENT1 expression or activity in the subject or patient sample is used to identify a subject or patient sample having low hENT1 expression or activity to identify a course of treatment for the subject. 
     
     
         13 . The use of  claim 12 , wherein the course of treatment is administration of gemcitabine-5′-elaidic acid ester, gemcitabine-N4-elaidic acid amide, cytarabine, cytarabine-5′-elaidic acid ester, ribavirin, ribavirin-5′-elaidic acid ester or 5-azacytidine-5′-elaidic acid ester. 
     
     
         14 . Use of the antibody of  claim 1  as a companion diagnostic for a cancer drug or an antiviral drug. 
     
     
         15 . The use of  claim 14 , wherein the cancer drug is gemcitabine-5′-elaidic acid ester, gemcitabine-N4-elaidic acid amide, cytarabine-5′-elaidic acid ester, ribavirin-5′-elaidic acid ester or 5-azacytidine-5′-elaidic acid ester. 
     
     
         16 . A method of alleviating a symptom of a clinical indication associated aberrant human Equilibrative Nucleoside Transporter 1 (hENT1) expression or activity in a subject, the method comprising administering an antagonist of hENT1 to a subject in need thereof in an amount sufficient to alleviate the symptom of the clinical indication associated aberrant hENT1 expression or activity. 
     
     
         17 . The method of  claim 16 , wherein said subject is a human. 
     
     
         18 . The method of  claim 16 , wherein said antagonist is a monoclonal antibody or antigen-binding fragment thereof. 
     
     
         19 . The method of  claim 18 , wherein said monoclonal antibody or antigen-binding fragment thereof comprises a variable heavy chain complementarity determining region 1 (VH CDR1) sequence comprising the amino acid sequence GYTFTDYE (SEQ ID NO: 10); a variable heavy chain complementarity determining region 2 (VH CDR2) sequence comprising the amino acid sequence IDPETGAI (SEQ ID NO: 11) or the amino acid sequence IDPETGKT (SEQ ID NO: 40); and a variable heavy chain complementarity determining region 3 (VH CDR3) sequence comprising the amino acid sequence TREFTY (SEQ ID NO: 12) or the amino acid sequence TRELTY (SEQ ID NO: 41), and a variable light chain complementarity determining region 1 (VL CDR1) sequence comprising the amino acid sequence QSLLFSNGKTY (SEQ ID NO: 24); a variable light chain complementarity determining region 2 (VL CDR2) sequence comprising the amino acid sequence LVS (SEQ ID NO: 25); and a variable light chain complementarity determining region 3 (VL CDR3) sequence comprising the amino acid sequence VQGTHFPWT (SEQ ID NO: 26), and wherein said antibody or antigen-binding fragment thereof binds hENT1 or a biologically active fragment thereof. 
     
     
         20 . The method of  claim 19 , wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable sequence comprising an amino acid sequence selected from SEQ ID NO: 2, 4, 6, 8, 9, 28, 30, 32, 34, 36, 38, 39, 51 and 53, and a light chain variable sequence comprising the amino acid sequence selected from SEQ ID NO: 14, 16, 18, 20, 22, 23, 43, 45, 47 and 49. 
     
     
         21 . The method of  claim 19 , wherein said antibody is an IgG isotype or an antigen-binding fragment of an IgG isotype antibody. 
     
     
         22 . The method of  claim 21 , wherein said antibody is an IgG1 isotype or antigen-binding fragment of an IgG1 isotype antibody. 
     
     
         23 . The method of  claim 22 , wherein said antibody is an IgG1 kappa isotype or antigen-binding fragment of an IgG1 kappa isotype antibody.

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