Anti-pd-l1 monoclonal antibodies and fragments thereof

Abstract

The present invention is based, in part, on the discovery of monoclonal antibodies that specifically bind to the cytoplasmic domain of PD-L1 antibodies useful for diagnostic, prognostic, and therapeutic applications, as well as immunoglobulins, polypeptides, and nucleic acids thereof.

1 - 14 . (canceled) 
     
     
         15 . A method of detecting the presence or level of a PD-L1 polypeptide said method comprising obtaining a sample and detecting said polypeptide in a sample by use of at least one monoclonal antibody, or antigen-binding fragment thereof, wherein the at least one monoclonal antibody comprises:
 i) a heavy chain sequence with at least about 95% identity to a heavy chain sequence selected from the group consisting of the sequences listed in Table 1;   ii) a light chain sequence with at least about 95% identity to a light chain sequence selected from the group consisting of the sequences listed in Table 1;   iii) a heavy chain CDR sequence with at least about 95% identity to a heavy chain CDR sequence selected from the group consisting of the sequences listed in Table 1;   iv) a light chain CDR sequence with at least about 95% identity to a light chain CDR sequence selected from the group consisting of the sequences listed in Table 1;   v) a heavy chain sequence selected from the group consisting of the sequences listed in Table 1;   vi) a light chain sequence selected from the group consisting of the sequences listed in Table 1;   vii) a heavy chain CDR sequence selected from the group consisting of the CDR sequences listed in Table 1; or   viii) a light chain CDR sequence selected from the group consisting the CDR sequences listed in Table 1.   
     
     
         16 . The method of  claim 15 , wherein the at least one monoclonal antibody, or antigen-binding fragment thereof, forms a complex with a PD-L1 polypeptide and the complex is detected in the form of an enzyme linked immunosorbent assay (ELISA), radioimmune assay (RIA), immunochemically, or using an intracellular flow assay. 
     
     
         17 . A method for monitoring the progression of a disorder associated with aberrant PD-L1 expression in a subject, the method comprising:
 a) detecting in a subject sample at a first point in time the level of expression of PD-L1 using at least one monoclonal antibody, or antigen-binding fragment thereof, according to  claim 15 ;   b) repeating step a) at a subsequent point in time; and   c) comparing the level of expression of said PD-L1 detected in steps a) and b) to monitor the progression of the disorder in the subject, optionally wherein the subject is a human.   
     
     
         18 . The method of  claim 17 , wherein between the first point in time and the subsequent point in time, the subject has undergone treatment to ameliorate the disorder. 
     
     
         19 . A method for predicting the clinical outcome of a subject afflicted with a disorder associated with aberrant PD-L1, the method comprising:
 a) determining the level of expression of PD-L1 in a patient sample using at least one monoclonal antibody, or antigen-binding fragment thereof, according to  claim 15 ;   b) determining the level of expression of PD-L1 in a sample from a control subject having a good clinical outcome using at least one monoclonal antibody, or antigen-binding fragment thereof, according to  claim 15 ; and   c) comparing the level of expression of PD-L1 in the patient sample and in the sample from the control subject;   
       wherein a significantly higher level of expression in the patient sample as compared to the expression level in the sample from the control subject is an indication that the patient has a poor clinical outcome, optionally wherein the subject is a human. 
     
     
         20 . A method of assessing the efficacy of a therapy for a disorder associated with aberrant PD-L1 in a subject, the method comprising comparing:
 a) the level of expression of PD-L1 using at least one monoclonal antibody, or antigen-binding fragment thereof, detected according to  claim 15 , in a first sample obtained from the subject prior to providing at least a portion of the therapy to the subject, and   b) the level of expression of PD-L1 in a second sample obtained from the subject following provision of the portion of the therapy,   
       wherein a significantly lower level of expression of PD-L1 in the second sample, relative to the first sample, is an indication that the therapy is efficacious for inhibiting the disorder in the subject, optionally wherein the subject is a human. 
     
     
         21 . A method of assessing the efficacy of a test compound for inhibiting a disorder associated with aberrant PD-L1 in a subject, the method comprising comparing:
 a) the level of expression of PD-L1 using at least one monoclonal antibody, or antigen-binding fragment thereof, detected according to  claim 15 , in a first sample obtained from the subject and exposed to the test compound; and   b) the level of expression of PD-L1 in a second sample obtained from the subject,   
       wherein the second sample is not exposed to the test compound, and a significantly lower level of expression of PD-L1, relative to the second sample, is an indication that the test compound is efficacious for inhibiting the disorder in the subject, optionally wherein the subject is a human. 
     
     
         22 . The method of  claim 21 , wherein the first and second samples are portions of a single sample obtained from the subject or portions of pooled samples obtained from the subject. 
     
     
         23 . The method of  claim 17 , wherein the disorder is a cancer. 
     
     
         24 . The method of  claim 17 , wherein the sample comprises cells, serum, peritumoral tissue, and/or intratumoral tissue obtained from the subject. 
     
     
         25 . The method of  claim 17 , wherein said significant increase comprises an at least twenty percent increase between the level of expression of PD-L1 in the subject sample relative to the normal level of expression of PD-L1 in the sample from the control subject. 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 19 , wherein the disorder is a cancer. 
     
     
         28 . The method of  claim 20 , wherein the disorder is a cancer. 
     
     
         29 . The method of  claim 21 , wherein the disorder is a cancer. 
     
     
         30 . The method of  claim 19 , wherein the sample comprises cells, serum, peritumoral tissue, and/or intratumoral tissue obtained from the subject. 
     
     
         31 . The method of  claim 20 , wherein the sample comprises cells, serum, peritumoral tissue, and/or intratumoral tissue obtained from the subject. 
     
     
         32 . The method of  claim 21 , wherein the sample comprises cells, serum, peritumoral tissue, and/or intratumoral tissue obtained from the subject. 
     
     
         33 . The method of  claim 19 , wherein said significant increase comprises an at least twenty percent increase between the level of expression of PD-L1 in the subject sample relative to the normal level of expression of PD-L1 in the sample from the control subject. 
     
     
         34 . The method of  claim 20 , wherein said significant increase comprises an at least twenty percent increase between the level of expression of PD-L1 in the subject sample relative to the normal level of expression of PD-L1 in the sample from the control subject. 
     
     
         35 . The method of  claim 21 , wherein said significant increase comprises an at least twenty percent increase between the level of expression of PD-L1 in the subject sample relative to the normal level of expression of PD-L1 in the sample from the control subject.