Anti-pd-l1 antibodies and methods of using the same for detection of pd-l1

Abstract

The present application relates to anti-PD-L1 antibodies and their use to detect PD-L1 in a sample from a subject. In some embodiments, the subject has been treated with a therapeutic anti-PD-L1 antibody and an anti-PD-L1 described herein does not compete for binding to PD-L1 with the therapeutic anti-PD-L1 antibody. In some embodiments, the anti-PD-L1 antibody is linked to a detectable moiety, such as a fluorophore and the anti-PD-L1 antibody is used to detect PD-L1 in a subject using flow cytometry.

1 . An isolated anti-PD-L1 antibody, or an antigen-binding fragment thereof, wherein the antibody comprises:
 (a) a heavy chain variable region comprising:
 (i) HVR-H1 comprising the amino acid sequence TSWMN (SEQ ID NO:1); 
 (ii) HVR-H2 comprising the amino acid sequence RIYPRDGDTYYNGKFKD (SEQ ID NO:2); and 
 (iii) HVR-H3 comprising the amino acid sequence NPGGYYFDY (SEQ ID NO:3); and 
   (b) a light chain variable region comprising:
 (i) HVR-L1 comprising the amino acid sequence RASQDIHTYLN (SEQ ID NO:4); 
 (ii) HVR-L2 comprising the amino acid sequence YTSRLHS (SEQ ID NO:5); and 
 (iii) HVR-L3 comprising the amino acid sequence QQVSSLPPWT (SEQ ID NO:6). 
   
     
     
         2 - 11 . (canceled) 
     
     
         12 . An isolated nucleic acid encoding the antibody or antigen-binding fragment of  claim 1 . 
     
     
         13 . A vector comprising the nucleic acid of  claim 12 . 
     
     
         14 . The vector of  claim 13 , wherein the vector is an expression vector. 
     
     
         15 . A host cell comprising the vector nucleic acid of  claim 14 . 
     
     
         16 . A method of producing an anti-PD-L1 antibody or antigen-binding fragment thereof, comprising culturing the host cell of  claim 15  under a condition suitable for production of the anti-PD-L1 antibody or antigen-binding fragment thereof. 
     
     
         17 . (canceled) 
     
     
         18 . A method for detecting PD-L1 in a biological sample obtained from a subject, the method comprising:
 (a) contacting the biological sample with the antibody or antigen-binding fragment of  claim 1 ; and   (b) detecting binding of the antibody or antigen-binding fragment to PD-L1 in the biological sample, thereby detecting PD-L1 in the biological sample.   
     
     
         19 - 29 . (canceled) 
     
     
         30 . A method of monitoring cancer treatment in a subject, the method comprising:
 (a) contacting a first biological sample with the antibody or antigen-binding fragment of  claim 1 ;   (b) detecting binding of the antibody or antigen-binding fragment to PD-L1 in the first biological sample;   (c) determining the amount of PD-L1 present in the first biological sample;   (d) contacting a second biological sample with the antibody or antigen-binding fragment of  claim 1 , wherein the second biological sample is obtained after treatment with a therapeutic anti-PD-L1 antibody or antigen-binding fragment thereof;   (e) detecting binding of the antibody or antigen-binding fragment to PD-L1 in the second biological sample;   (f) determining the amount of PD-L1 present in the second biological sample;   (g) comparing the amount of PD-L1 present in the first biological sample to the amount of PD-L1 present in the second biological sample.   
     
     
         31 . The method of  claim 30 , wherein an increase in the amount of PD-L1 present in the second biological sample compared to the first biological sample indicates that the patient is not responding to treatment with the therapeutic anti-PD-L1 antibody. 
     
     
         32 . The method of  claim 30 , wherein a decrease in the amount of PD-L1 present in the second biological sample compared to the first biological sample indicates that the patient is responding to treatment with the therapeutic anti-PD-L1 antibody. 
     
     
         33 - 44 . (canceled) 
     
     
         45 . The method of  claim 18 , wherein the subject is a human. 
     
     
         46 . A composition comprising the antibody or antigen-binding fragment of  claim 1 . 
     
     
         47 . A kit for detecting PD-L1 in a biological sample comprising the antibody of  claim 1 .