Anti-c10orf54 antibodies and uses thereof

Abstract

The present disclosure relates generally to anti-C10orf54 antibodies, including antibody-drug conjugates comprising the antibodies, and methods of their use.

1 . An isolated antibody that binds to C10orf54, wherein the antibody comprises:
 (a) a heavy chain variable (V H ) region comprising:   (1) a V H  CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:36, 30, 59-62, and 33;   (2) a V H  CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886-894, and 1070-1078; and   (3) a V H  CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:38, 32, 319, 35, and 883-885;   and/or   (b) a light chain variable (V L ) region comprising:   (1) a V L  CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:45, 253-271, and 42;   (2) a V L  CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:46, 272-275, 40, 843-846, 43, and 1045-1048; and   (3) a V L  CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:47, 41, 44, and 1056-1058.   
     
     
         2 . The antibody of  claim 1 , wherein the antibody is humanized. 
     
     
         3 . The antibody of  claim 1 , wherein the V H  region further comprises:
 (1) a V H  FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 105, 55, 115-121, 39, 58, and 895-902;   (2) a V H  FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 106, 56, 122-124, 63, 64, and 323-326;   (3) a V H  FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, and 903-1030; and/or   (4) a V H  FR4 having an amino acid sequence of SEQ ID NO:54 or 320.   
     
     
         4 . The antibody of  claim 1 , wherein the V L  region further comprises:
 (1) a V L  FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:75, 252, 79, 277-283, 91, 1031-1037, and 1059-1061;   (2) a V L  FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:76, 80, 284, 92, 1038-1044, and 1062-1067;   (3) a V L  FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:77, 276, 81, 285-291, 93, 1049-1055, 1068, and 1069; and/or   (4) a V L  FR4 having an amino acid of SEQ ID NO:78.   
     
     
         5 .- 11 . (canceled) 
     
     
         12 . The antibody of  claim 1 , wherein the V H  region comprises the amino acid sequence of SEQ ID NO: 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 and/or the V L  region comprises the amino acid sequence of SEQ ID NO:24, 25, 26, 27, 28 or 29. 
     
     
         13 - 29 . (canceled) 
     
     
         30 . An isolated antibody that binds to C10orf54, wherein the antibody comprises:
 (a) a heavy chain variable (V H ) region comprising:   (1) a V H  CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 36, 1081, 1086, 1087, 1092, 30, 1099, 1104, 1105, 1110, 33, 1117, 1122, 1123 and 1128;   (2) a V H  CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 37, 1082, 1088, 1093, 1098, 31, 1100, 1106, 1111, 1116, 34, 1118, 1124, 1129 and 1134; and   (3) a V H  CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 38, 1083, 1089, 1094, 32, 1101, 1107, 1112, 35, 1119, 1125 and 1130;   and/or   (b) a light chain variable (V L ) region comprising:   (1) a V L  CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 45, 1084, 1090, 1095, 1102, 1108, 1113, 42, 1120, 1126 and 1131;   (2) a V L  CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 46, 1085, 1096, 40, 1103, 1114, 43, 1121 and 1132; and   (3) a V L  CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 47, 1091, 1097, 41, 1109, 1115, 44, 1127 and 1133.   
     
     
         31 .- 49 . (canceled) 
     
     
         50 . An isolated antibody that binds to a C10orf54 epitope, wherein the binding to the epitope competitively blocks the binding of the antibody of  claim 1  in a dose-dependent manner. 
     
     
         51 . An antibody of  claim 1 , wherein the antibody is conjugated or recombinantly fused to a diagnostic agent, detectable agent or therapeutic agent. 
     
     
         52 - 55 . (canceled) 
     
     
         56 . A composition comprising the antibody of  claim 1 . 
     
     
         57 . (canceled) 
     
     
         58 . An isolated nucleic acid molecule comprising or consisting of a nucleic acid sequence that encodes the V H  region or V L  region of  claim 1 . 
     
     
         59 . A vector comprising the nucleic acid molecule of  claim 58 . 
     
     
         60 . A host cell comprising the vector of  claim 59 . 
     
     
         61 . A method of producing an antibody comprising culturing the host cell of  claim 60  under conditions that promote the production of the antibody. 
     
     
         62 . A method of treating, preventing or alleviating one or more symptoms of a disease comprising administering a therapeutically effective amount of the composition of  claim 56  to a subject, thereby treating, preventing or alleviating one or more symptoms of the disease. 
     
     
         63 - 66 . (canceled) 
     
     
         67 . A method of inhibiting the growth of a cell having cell surface expression of C10orf54 comprising contacting the cell with an effective amount of the composition of  claim 56 . 
     
     
         68 - 69 . (canceled) 
     
     
         70 . A method of modulating an immune response in a subject comprising administering an effective amount of the composition of  claim 56  to a subject. 
     
     
         71 . (canceled) 
     
     
         72 . A method for detecting C10orf54 in a sample comprising contacting the sample with the antibody of  claim 1 , wherein said antibody is conjugated or recombinantly fused to a cytotoxin or to a detectable agent. 
     
     
         73 . (canceled) 
     
     
         74 . A method of treating cancer comprising administering to a subject a therapeutically effective amount of an anti-C10orf54 antibody or an antibody-drug conjugate comprising an anti-C10orf54 antibody, wherein the anti-C10orf54 antibody is the anti-C10orf54 antibody of  claim 1 . 
     
     
         75 . A method of killing a tumor cell comprising contacting a C10orf54-expressing tumor cell with an amount of an anti-C10orf54 antibody or antibody-drug conjugate comprising an anti-C10orf54 antibody effective to kill the tumor cell, wherein the anti-C10orf54 antibody is the anti-C10orf54 antibody of  claim 1 . 
     
     
         76 . A kit comprising the antibody of  claim 1 . 
     
     
         77 . (canceled) 
     
     
         78 . An antibody-drug conjugate of the following formulas (Ia) or (Ib): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof; 
         wherein: 
         A is an antibody or antibody fragment according to  claim 1 ; 
         the two depicted cysteine residues are from an opened cysteine-cysteine disulfide bond in A; 
         each X and X′ is independently O, S, NH, or NR 1  wherein R 1  is C 1-6  alkyl; 
         W a  is —N—, —CH—, —CHCH 2 —, ═C(R 2 )—, or ═CHCH(R 2 )—; W b —NH—, —N(R 1 )—, —CH 2 —, —CH 2 —NH—, —CH 2 —N(R 1 )—, —CH 2 CH 2 —, —CH(R 2 )—, or —CH 2 CH(R 2 )—; wherein R 1  and R 2  are independently C 1-6  alkyl; 
         CTX is a cytotoxin; 
         R is any chemical group; or R is absent; 
         each L 1 , L 2  and L 3  is independently a linker selected from the group consisting of —O—, —C(O)—, —S—, —S(O)—, —S(O) 2 —, —NH—, —NCH 3 —, —(CH 2 ) q —, —NH(CH 2 ) 2 NH—, —OC(O)—, —CO 2 —, —NHCH 2 CH 2 C(O)—, —C(O)NHCH 2 CH 2 NH—, —NHCH 2 C(O)—, —NHC(O)—, —C(O)NH—, —NCH 3 C(O)—, —C(O)NCH 3 —, —(CH 2 CH 2 O) p , —(CH 2 CH 2 O) p CH 2 CH 2 —, —CH 2 CH 2 —(CH 2 CH 2 O) p —, —OCH(CH 2 O—) 2 , -(AA) r -, cyclopentanyl, cyclohexanyl, unsubstituted phenylenyl, and phenylenyl substituted by 1 or 2 substituents selected from the group consisting of halo, CF 3 —, CF 3 O—, CH 3 O—, —C(O)OH, —C(O)OC 1-3  alkyl, —C(O)CH 3 , —CN, —NH—, —NH 2 , —O—, —OH, —NHCH 3 , —N(CH 3 ) 2 , and C 1-3  alkyl; 
         a, b and c are each independently an integer of 0, 1, 2 or 3, provided that at least one of a, b or c is 1; 
         each k and k′ is independently an integer of 0 or 1; 
         each p is independently an integer of 1 to 14; 
         each q is independently an integer from 1 to 12; 
         each AA is independently an amino acid; 
         each r is 1 to 12; 
         m is an integer of 1 to 4; 
         n is an integer of 1 to 4; and 
         the   bond represents a single or a double bond. 
       
     
     
         79 - 83 . (canceled)