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PMC:7228307 / 49161-54061 JSONTXT

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LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id tao:has_standard_notation
979 25-29 Gene denotes FcγR Gene:2213
984 728-732 Gene denotes FcγR Gene:2213
985 414-418 Gene denotes FcγR Gene:2213
986 270-274 Gene denotes FcγR Gene:2213
987 96-100 Gene denotes FcγR Gene:2213
1003 1261-1267 Gene denotes CTLA‐4 Gene:1493
1004 1275-1280 Gene denotes PD‐L1 Gene:29126
1005 1281-1285 Gene denotes PD‐1 Gene:5133
1006 1495-1499 Gene denotes PD‐1 Gene:5133
1007 1727-1733 Gene denotes CTLA‐4 Gene:1493
1008 1061-1065 Gene denotes FcγR Gene:2213
1009 924-928 Gene denotes FcγR Gene:2213
1010 815-819 Gene denotes FcγR Gene:2213
1011 1442-1455 Chemical denotes Pembrolizumab MESH:C582435
1012 1457-1466 Chemical denotes nivolumab MESH:D000077594
1013 1471-1481 Chemical denotes cemiplimab MESH:C000627974
1014 1703-1715 Chemical denotes tremelimumab MESH:C520704
1015 1383-1388 Disease denotes tumor MESH:D009369
1016 1530-1536 Disease denotes cancer MESH:D009369
1017 1629-1634 Mutation denotes S228P rs1469294455
1022 1951-1956 Gene denotes FcγRI Gene:2214
1023 2160-2165 Gene denotes FcγRI Gene:2214
1024 2243-2250 Gene denotes FcγRIIb Gene:2213
1025 2137-2141 Gene denotes PD‐1 Gene:5133
1031 2796-2801 Gene denotes PD‐L1 Gene:29126
1032 2866-2870 Gene denotes FcγR Gene:2213
1033 2694-2698 Gene denotes FcγR Gene:2213
1034 2650-2665 Chemical denotes N‐linked glycan
1035 2769-2781 Chemical denotes Atezolizumab MESH:C000594389
1044 3247-3251 Gene denotes FcγR Gene:2213
1045 3003-3007 Gene denotes FcγR Gene:2213
1046 2955-2959 Gene denotes FcγR Gene:2213
1047 3075-3082 Chemical denotes leucine MESH:D007930
1048 3150-3157 Chemical denotes alanine MESH:D000409
1049 3305-3315 Chemical denotes teplizumab MESH:C502540
1050 3320-3330 Chemical denotes spesolimab
1051 3159-3170 Mutation denotes L234A L235A p.L234,235A,A
1063 3609-3614 Gene denotes PD‐L1 Gene:29126
1064 3926-3929 Gene denotes C1q Gene:712
1065 3873-3877 Gene denotes FcγR Gene:2213
1066 3477-3481 Gene denotes FcγR Gene:2213
1067 3836-3840 Gene denotes FcγR Gene:2213
1068 3416-3420 Gene denotes FcγR Gene:2213
1069 3592-3602 Chemical denotes durvalumab MESH:C000613593
1070 3620-3631 Chemical denotes anifrolumab MESH:C582345
1071 3718-3723 Mutation denotes L234F p.L234F
1072 3757-3762 Mutation denotes L235E p.L235E
1073 3786-3791 Mutation denotes P331S p.P331S
1088 4021-4026 Gene denotes FcγRI Gene:2214
1089 4031-4038 Gene denotes FcγRIIb Gene:2213
1090 4294-4298 Gene denotes FcγR Gene:2213
1091 4093-4097 Gene denotes FcγR Gene:2213
1092 4596-4600 Gene denotes FcγR Gene:2213
1093 4418-4428 Chemical denotes disulfides MESH:D004220
1094 4054-4080 Disease denotes PD‐1 antibody tislelizumab MESH:D010300
1095 4209-4214 Mutation denotes E233P p.E233P
1096 4216-4221 Mutation denotes F234V rs755807976
1097 4223-4228 Mutation denotes L235A p.L235A
1098 4256-4261 Mutation denotes D265A p.D265A
1099 4359-4364 Mutation denotes S228P rs1469294455
1100 4377-4382 Mutation denotes L309V p.L309V
1101 4387-4392 Mutation denotes R409K p.R409K
1104 4820-4824 Gene denotes FcγR Gene:2213
1105 4689-4693 Gene denotes FcγR Gene:2213

LitCovid-PD-FMA-UBERON

Id Subject Object Predicate Lexical cue fma_id
T393 51-54 Body_part denotes IgG http://purl.org/sig/ont/fma/fma62872
T394 175-178 Body_part denotes IgG http://purl.org/sig/ont/fma/fma62872
T395 551-554 Body_part denotes IgG http://purl.org/sig/ont/fma/fma62872
T396 853-862 Body_part denotes backbones http://purl.org/sig/ont/fma/fma13478
T397 1009-1012 Body_part denotes IgG http://purl.org/sig/ont/fma/fma62872
T398 1151-1160 Body_part denotes backbones http://purl.org/sig/ont/fma/fma13478
T399 1432-1440 Body_part denotes backbone http://purl.org/sig/ont/fma/fma13478
T400 1734-1742 Body_part denotes antibody http://purl.org/sig/ont/fma/fma62871
T401 1764-1772 Body_part denotes backbone http://purl.org/sig/ont/fma/fma13478
T402 1815-1820 Body_part denotes cells http://purl.org/sig/ont/fma/fma68646
T403 2022-2032 Body_part denotes neutrophil http://purl.org/sig/ont/fma/fma62860
T404 2928-2938 Body_part denotes amino acid http://purl.org/sig/ont/fma/fma82739
T405 3075-3082 Body_part denotes leucine http://purl.org/sig/ont/fma/fma82757
T406 3150-3157 Body_part denotes alanine http://purl.org/sig/ont/fma/fma82749
T407 3387-3397 Body_part denotes amino acid http://purl.org/sig/ont/fma/fma82739
T408 3563-3574 Body_part denotes amino acids http://purl.org/sig/ont/fma/fma82739
T409 4059-4067 Body_part denotes antibody http://purl.org/sig/ont/fma/fma62871
T410 4489-4491 Body_part denotes Ig http://purl.org/sig/ont/fma/fma62871
T411 4768-4777 Body_part denotes backbones http://purl.org/sig/ont/fma/fma13478

LitCovid-PD-MONDO

Id Subject Object Predicate Lexical cue mondo_id
T100 138-141 Disease denotes MOA http://purl.obolibrary.org/obo/MONDO_0016702
T101 1383-1388 Disease denotes tumor http://purl.obolibrary.org/obo/MONDO_0005070
T102 1530-1536 Disease denotes cancer http://purl.obolibrary.org/obo/MONDO_0004992
T103 1792-1796 Disease denotes ADCC http://purl.obolibrary.org/obo/MONDO_0008734

LitCovid-PD-CLO

Id Subject Object Predicate Lexical cue
T841 25-27 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T842 96-98 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T843 145-146 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T844 239-242 http://purl.obolibrary.org/obo/CLO_0051582 denotes has
T845 270-272 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T846 414-416 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T847 584-586 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T848 619-621 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T849 685-692 http://purl.obolibrary.org/obo/CLO_0009985 denotes focused
T850 728-730 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T851 804-814 http://purl.obolibrary.org/obo/CLO_0001658 denotes activating
T852 815-817 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T853 820-823 http://purl.obolibrary.org/obo/CLO_0051582 denotes has
T854 875-876 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T855 913-923 http://purl.obolibrary.org/obo/CLO_0001658 denotes activating
T856 924-926 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T857 1061-1063 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T858 1261-1267 http://purl.obolibrary.org/obo/PR_000001852 denotes CTLA‐4
T859 1275-1280 http://purl.obolibrary.org/obo/CLO_0008407 denotes PD‐L1
T860 1332-1339 http://purl.obolibrary.org/obo/SO_0000418 denotes signals
T861 1604-1605 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T862 1727-1733 http://purl.obolibrary.org/obo/PR_000001852 denotes CTLA‐4
T863 1815-1820 http://purl.obolibrary.org/obo/GO_0005623 denotes cells
T864 1913-1923 http://purl.obolibrary.org/obo/CLO_0001658 denotes activating
T865 1934-1936 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T866 1951-1953 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T867 2033-2043 http://purl.obolibrary.org/obo/CLO_0001658 denotes activation
T868 2160-2162 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T869 2179-2187 http://purl.obolibrary.org/obo/CLO_0001658 denotes activity
T870 2243-2245 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T871 2580-2582 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T872 2586-2587 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T873 2694-2696 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T874 2736-2738 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T875 2752-2754 http://purl.obolibrary.org/obo/CLO_0001313 denotes 36
T876 2765-2768 http://purl.obolibrary.org/obo/CLO_0054060 denotes 102
T877 2796-2801 http://purl.obolibrary.org/obo/CLO_0008407 denotes PD‐L1
T878 2866-2868 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T879 2891-2901 http://purl.obolibrary.org/obo/CLO_0001658 denotes activation
T880 2925-2927 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T881 2955-2957 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T882 3003-3005 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T883 3017-3018 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T884 3129-3133 http://purl.obolibrary.org/obo/CLO_0007179 denotes L235
T885 3247-3249 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T886 3342-3343 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T887 3362-3365 http://purl.obolibrary.org/obo/CLO_0051582 denotes has
T888 3387-3406 http://purl.obolibrary.org/obo/CHEBI_33708 denotes amino acid residues
T889 3387-3406 http://purl.obolibrary.org/obo/PR_000036907 denotes amino acid residues
T890 3416-3418 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T891 3477-3479 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T892 3609-3614 http://purl.obolibrary.org/obo/CLO_0008407 denotes PD‐L1
T893 3836-3838 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T894 3873-3875 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T895 3930-3940 http://purl.obolibrary.org/obo/CLO_0001658 denotes activation
T896 4021-4023 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T897 4031-4033 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T898 4081-4084 http://purl.obolibrary.org/obo/CLO_0051582 denotes has
T899 4093-4095 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T900 4146-4150 http://purl.obolibrary.org/obo/CLO_0007179 denotes L235
T901 4206-4207 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T902 4286-4287 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T903 4294-4296 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T904 4323-4326 http://purl.obolibrary.org/obo/CLO_0051582 denotes has
T905 4574-4575 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T906 4596-4598 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T907 4624-4634 http://purl.obolibrary.org/obo/CLO_0001658 denotes activation
T908 4644-4646 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T909 4689-4691 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc
T910 4788-4789 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T911 4820-4822 http://purl.obolibrary.org/obo/CLO_0052676 denotes Fc

LitCovid-PD-CHEBI

Id Subject Object Predicate Lexical cue chebi_id
T249 675-679 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T3637 1226-1236 Chemical denotes inhibitors http://purl.obolibrary.org/obo/CHEBI_35222
T24725 1275-1277 Chemical denotes PD http://purl.obolibrary.org/obo/CHEBI_74756
T35015 1281-1283 Chemical denotes PD http://purl.obolibrary.org/obo/CHEBI_74756
T38212 1442-1455 Chemical denotes Pembrolizumab http://purl.obolibrary.org/obo/CHEBI_82976
T9178 1495-1497 Chemical denotes PD http://purl.obolibrary.org/obo/CHEBI_74756
T92845 1693-1702 Chemical denotes inhibitor http://purl.obolibrary.org/obo/CHEBI_35222
T60873 1954-1956 Chemical denotes RI http://purl.obolibrary.org/obo/CHEBI_73814|http://purl.obolibrary.org/obo/CHEBI_8753
T66616 1995-2003 Chemical denotes effector http://purl.obolibrary.org/obo/CHEBI_35224
T93768 2137-2139 Chemical denotes PD http://purl.obolibrary.org/obo/CHEBI_74756
T92385 2163-2165 Chemical denotes RI http://purl.obolibrary.org/obo/CHEBI_73814|http://purl.obolibrary.org/obo/CHEBI_8753
T98482 2796-2798 Chemical denotes PD http://purl.obolibrary.org/obo/CHEBI_74756
T9506 2813-2822 Chemical denotes inhibitor http://purl.obolibrary.org/obo/CHEBI_35222
T68471 2928-2938 Chemical denotes amino acid http://purl.obolibrary.org/obo/CHEBI_33709
T62086 2928-2933 Chemical denotes amino http://purl.obolibrary.org/obo/CHEBI_46882
T40175 2934-2938 Chemical denotes acid http://purl.obolibrary.org/obo/CHEBI_37527
T80744 3075-3082 Chemical denotes leucine http://purl.obolibrary.org/obo/CHEBI_25017
T54623 3150-3157 Chemical denotes alanine http://purl.obolibrary.org/obo/CHEBI_16449
T5000 3387-3397 Chemical denotes amino acid http://purl.obolibrary.org/obo/CHEBI_33709
T20266 3387-3392 Chemical denotes amino http://purl.obolibrary.org/obo/CHEBI_46882
T44260 3393-3397 Chemical denotes acid http://purl.obolibrary.org/obo/CHEBI_37527
T10443 3563-3574 Chemical denotes amino acids http://purl.obolibrary.org/obo/CHEBI_33709
T57589 3563-3568 Chemical denotes amino http://purl.obolibrary.org/obo/CHEBI_46882
T8912 3569-3574 Chemical denotes acids http://purl.obolibrary.org/obo/CHEBI_37527
T75315 3609-3611 Chemical denotes PD http://purl.obolibrary.org/obo/CHEBI_74756
T36188 3638-3648 Chemical denotes interferon http://purl.obolibrary.org/obo/CHEBI_52999
T28 4024-4026 Chemical denotes RI http://purl.obolibrary.org/obo/CHEBI_73814|http://purl.obolibrary.org/obo/CHEBI_8753
T85014 4054-4056 Chemical denotes PD http://purl.obolibrary.org/obo/CHEBI_74756
T2607 4418-4428 Chemical denotes disulfides http://purl.obolibrary.org/obo/CHEBI_35489|http://purl.obolibrary.org/obo/CHEBI_48343
T70545 4694-4702 Chemical denotes effector http://purl.obolibrary.org/obo/CHEBI_35224
T34 4881-4889 Chemical denotes effector http://purl.obolibrary.org/obo/CHEBI_35224

LitCovid-sample-PD-IDO

Id Subject Object Predicate Lexical cue
T225 38-47 http://purl.obolibrary.org/obo/BFO_0000034 denotes functions
T226 1815-1820 http://purl.obolibrary.org/obo/CL_0000000 denotes cells
T227 2004-2013 http://purl.obolibrary.org/obo/BFO_0000034 denotes functions
T228 4703-4712 http://purl.obolibrary.org/obo/BFO_0000034 denotes functions
T229 4890-4899 http://purl.obolibrary.org/obo/BFO_0000034 denotes functions

LitCovid-sample-CHEBI

Id Subject Object Predicate Lexical cue chebi_id
T54 2928-2938 Chemical denotes amino acid http://purl.obolibrary.org/obo/CHEBI_33709
T55 3075-3082 Chemical denotes leucine http://purl.obolibrary.org/obo/CHEBI_25017
T56 3150-3157 Chemical denotes alanine http://purl.obolibrary.org/obo/CHEBI_16449
T57 3387-3397 Chemical denotes amino acid http://purl.obolibrary.org/obo/CHEBI_33709
T58 3563-3574 Chemical denotes amino acids http://purl.obolibrary.org/obo/CHEBI_33709
T59 4418-4428 Chemical denotes disulfides http://purl.obolibrary.org/obo/CHEBI_35489|http://purl.obolibrary.org/obo/CHEBI_48343

LitCovid-sample-Pubtator

Id Subject Object Predicate Lexical cue pubann:denotes pubann:has_HGVS_notation
1003 1261-1267 Gene denotes CTLA‐4 Gene:1493
1004 1275-1280 Gene denotes PD‐L1 Gene:29126
1005 1281-1285 Gene denotes PD‐1 Gene:5133
1006 1495-1499 Gene denotes PD‐1 Gene:5133
1007 1727-1733 Gene denotes CTLA‐4 Gene:1493
1008 1061-1065 Gene denotes FcγR Gene:2213
1009 924-928 Gene denotes FcγR Gene:2213
1010 815-819 Gene denotes FcγR Gene:2213
1011 1442-1455 Chemical denotes Pembrolizumab MESH:C582435
1012 1457-1466 Chemical denotes nivolumab MESH:D000077594
1013 1471-1481 Chemical denotes cemiplimab MESH:C000627974
1014 1703-1715 Chemical denotes tremelimumab MESH:C520704
1015 1383-1388 Disease denotes tumor MESH:D009369
1016 1530-1536 Disease denotes cancer MESH:D009369
1017 1629-1634 Mutation denotes S228P rs1469294455
1022 1951-1956 Gene denotes FcγRI Gene:2214
1023 2160-2165 Gene denotes FcγRI Gene:2214
1024 2243-2250 Gene denotes FcγRIIb Gene:2213
1025 2137-2141 Gene denotes PD‐1 Gene:5133
1031 2796-2801 Gene denotes PD‐L1 Gene:29126
1032 2866-2870 Gene denotes FcγR Gene:2213
1033 2694-2698 Gene denotes FcγR Gene:2213
1034 2650-2665 Chemical denotes N‐linked glycan
1035 2769-2781 Chemical denotes Atezolizumab MESH:C000594389
1044 3247-3251 Gene denotes FcγR Gene:2213
1045 3003-3007 Gene denotes FcγR Gene:2213
1046 2955-2959 Gene denotes FcγR Gene:2213
1047 3075-3082 Chemical denotes leucine MESH:D007930
1048 3150-3157 Chemical denotes alanine MESH:D000409
1049 3305-3315 Chemical denotes teplizumab MESH:C502540
1050 3320-3330 Chemical denotes spesolimab
1051 3159-3170 Mutation denotes L234A L235A p.L234,235A,A
1063 3609-3614 Gene denotes PD‐L1 Gene:29126
1064 3926-3929 Gene denotes C1q Gene:712
1065 3873-3877 Gene denotes FcγR Gene:2213
1066 3477-3481 Gene denotes FcγR Gene:2213
1067 3836-3840 Gene denotes FcγR Gene:2213
1068 3416-3420 Gene denotes FcγR Gene:2213
1069 3592-3602 Chemical denotes durvalumab MESH:C000613593
1070 3620-3631 Chemical denotes anifrolumab MESH:C582345
1071 3718-3723 Mutation denotes L234F p.L234F
1072 3757-3762 Mutation denotes L235E p.L235E
1073 3786-3791 Mutation denotes P331S p.P331S
1088 4021-4026 Gene denotes FcγRI Gene:2214
1089 4031-4038 Gene denotes FcγRIIb Gene:2213
1090 4294-4298 Gene denotes FcγR Gene:2213
1091 4093-4097 Gene denotes FcγR Gene:2213
1092 4596-4600 Gene denotes FcγR Gene:2213
1093 4418-4428 Chemical denotes disulfides MESH:D004220
1094 4054-4080 Disease denotes PD‐1 antibody tislelizumab MESH:D010300
1095 4209-4214 Mutation denotes E233P p.E233P
1096 4216-4221 Mutation denotes F234V rs755807976
1097 4223-4228 Mutation denotes L235A p.L235A
1098 4256-4261 Mutation denotes D265A p.D265A
1099 4359-4364 Mutation denotes S228P rs1469294455
1100 4377-4382 Mutation denotes L309V p.L309V
1101 4387-4392 Mutation denotes R409K p.R409K
1104 4820-4824 Gene denotes FcγR Gene:2213
1105 4689-4693 Gene denotes FcγR Gene:2213
984 728-732 Gene denotes FcγR Gene:2213
985 414-418 Gene denotes FcγR Gene:2213
986 270-274 Gene denotes FcγR Gene:2213
987 96-100 Gene denotes FcγR Gene:2213

LitCovid-sample-sentences

Id Subject Object Predicate Lexical cue
T282 0-54 Sentence denotes Attenuating and ablating FcγR‐related functions of IgG
T283 55-163 Sentence denotes There are circumstances where binding to FcγR is unnecessary or undesirable in the MOA of a therapeutic mAb.
T284 164-501 Sentence denotes Unmodified IgG irrespective of its subclass or intended therapeutic effect has the potential to engage an FcγR which may lead to suboptimal therapeutic performance or to unexpected and catastrophic consequences.57, 59 Clearly reducing or eliminating FcγR interactions, when they are not required for therapeutic effect, may be desirable.
T285 502-594 Sentence denotes Indeed, this had been addressed by the choice of IgG subclass or by modifying the Fc region.
T286 595-756 Sentence denotes Indeed, most efforts in Fc engineering mAbs that have translated to an approved drug have focused on the reduction or elimination of FcγR interactions (Table 4).
T287 757-1024 Sentence denotes One approach to minimize interactions with the activating FcγR has been the use of IgG4 or IgG2 backbones, which show a more restricted specificity for the activating FcγR and consequently have been traditionally, and simplistically, viewed as “inert” IgG subclasses.
T288 1025-1206 Sentence denotes Notwithstanding the unexpected, and FcγR‐dependent, severe adverse reaction induced by the IgG4 TGN1412 mAb, the IgG4 or IgG2 backbones have been successfully used in many settings.
T289 1207-1441 Sentence denotes Indeed, checkpoint inhibitors, such as mAbs targeting CTLA‐4 or the PD‐L1/PD‐1 interaction for the suppression of inhibitory signals that contribute to immune tolerance in the tumor microenvironment, are formatted on an IgG4 backbone.
T290 1442-1666 Sentence denotes Pembrolizumab, nivolumab and cemiplimab are all anti‐PD‐1 antibodies currently used for cancer therapy and have been formatted on an IgG4 backbone95, 96, 97 with a stabilized core hinge (S228P) to prevent half‐IgG4 exchange.
T291 1667-1823 Sentence denotes Similarly, the checkpoint inhibitor tremelimumab is an anti‐CTLA‐4 antibody formatted on an IgG2 backbone to avoid potential ADCC killing of target cells.98
T292 1824-1895 Sentence denotes However, the use of IgG2 and IgG4 as “inert” subclasses is problematic.
T293 1896-2291 Sentence denotes Both bind to the activating receptors FcγRIIa‐H131 and FcγRI, respectively (Table 2), and initiate effector functions such as neutrophil activation and apoptosis induction.75, 99 Interestingly, in experimental systems, cross‐linking of anti‐PD‐1 IgG4‐based mAb by FcγRI switched its activity from blocking to activatory.10 Moreover, IgG4 binds to FcγRIIb, which may scaffold the therapeutic mAb.
T294 2292-2609 Sentence denotes Although scaffolding may be beneficial in some contexts, for example, in immune agonism,43 it can be disastrous and unexpected in others as it was for the anti‐CD28 TGN1412 mAb.59 Thus, the IgG2 and IgG4 subclasses are not the optimum choice for “FcR‐inactive” mAbs, and so modifying the Fc is a more direct approach.
T295 2610-2904 Sentence denotes The complete removal of the heavy‐chain N‐linked glycan is well known to ablate all FcγR binding by dramatically altering the Fc conformation.36, 67, 101, 102 Atezolizumab, an IgG1 anti‐PD‐L1 checkpoint inhibitor mAb, utilizes this strategy and eliminates FcγR and also complement activation.13
T296 2905-3016 Sentence denotes Modification to the Fc amino acid sequence of the FcγR‐contact regions can also be used to reduce FcγR binding.
T297 3017-3172 Sentence denotes A widely used modification of IgG1 is the substitution of leucine 234 and 235 in the lower hinge sequence (L234 L235 G236 G237) with alanine (L234A L235A).
T298 3173-3341 Sentence denotes It is often referred to as the “LALA mutation” and effectively eliminates FcγR binding by more than 100 fold104, 105 and is used in teplizumab and spesolimab (Table 4).
T299 3342-3546 Sentence denotes A separate strategy has used combinations of amino acid residues from the FcγR‐binding regions of IgG2 and IgG4, which have restricted FcγR specificity, together with other binding‐inactivating mutations.
T300 3547-3725 Sentence denotes The lower hinge amino acids of the IgG1 mAbs durvalumab (anti‐PD‐L1) and anifrolumab (anti‐interferon‐α receptor; Table 4) were modified to mimic the lower hinge of IgG4 (L234F).
T301 3726-3943 Sentence denotes They additionally incorporated L235E in the lower hinge and P331S in the F/G loop of the CH2 domain to ablate FcγR binding by disrupting two major FcγR contact sites7 and also coincidently decreasing C1q activation.16
T302 3944-4039 Sentence denotes IgG4 mAbs have been similarly engineered to eliminate their interaction with FcγRI and FcγRIIb.
T303 4040-4314 Sentence denotes The IgG4 anti‐PD‐1 antibody tislelizumab has had its FcγR contact residues in the lower hinge E233, F234, L235 substituted with the equivalent residues of IgG2 P, V, A (E233P, F234V, L235A) as well as the additional D265A mutation which disrupts a major FcγR contact in CH2.
T304 4315-4532 Sentence denotes It also has substitutions in the core hinge S228P and the CH3 L309V and R409K to stabilize the H‐chain disulfides and CH3 interactions, respectively, thereby preventing half‐Ig exchange characteristic of natural IgG4.
T305 4533-4637 Sentence denotes Collectively, these modifications create a stable IgG4 with no FcγR binding nor complement activation.17
T306 4638-4900 Sentence denotes Thus, Fc engineering is an effective way to remove FcγR effector functions and may be preferable to using unmodified IgG2 or IgG4 backbones that have a more restricted repertoire of FcγR interactions but which are still able to induce certain effector functions.

LitCovid-sample-UniProt

Id Subject Object Predicate Lexical cue uniprot_id
T612 1261-1267 Protein denotes CTLA‐4 https://www.uniprot.org/uniprot/Q9XSI1|https://www.uniprot.org/uniprot/Q9UKN9|https://www.uniprot.org/uniprot/Q9TT02|https://www.uniprot.org/uniprot/Q9QZZ7|https://www.uniprot.org/uniprot/Q9MYX7|https://www.uniprot.org/uniprot/Q96P43|https://www.uniprot.org/uniprot/Q8WXJ1|https://www.uniprot.org/uniprot/Q5S005|https://www.uniprot.org/uniprot/Q53TD5|https://www.uniprot.org/uniprot/Q52MC1|https://www.uniprot.org/uniprot/Q0PP65|https://www.uniprot.org/uniprot/P42072|https://www.uniprot.org/uniprot/P16410|https://www.uniprot.org/uniprot/P09793|https://www.uniprot.org/uniprot/O95653|https://www.uniprot.org/uniprot/E9PDH0|https://www.uniprot.org/uniprot/A0N1S0
T629 1275-1280 Protein denotes PD‐L1 https://www.uniprot.org/uniprot/Q9NZQ7|https://www.uniprot.org/uniprot/Q9NUZ5|https://www.uniprot.org/uniprot/Q9EP73|https://www.uniprot.org/uniprot/Q6WEX4|https://www.uniprot.org/uniprot/Q66RK1|https://www.uniprot.org/uniprot/Q2V8D5|https://www.uniprot.org/uniprot/Q14CJ2|https://www.uniprot.org/uniprot/B4DU27|https://www.uniprot.org/uniprot/B2RBA2
T638 1281-1285 Protein denotes PD‐1 https://www.uniprot.org/uniprot/Q7M4M5|https://www.uniprot.org/uniprot/Q6NZ54|https://www.uniprot.org/uniprot/Q3KQW2|https://www.uniprot.org/uniprot/P18621|https://www.uniprot.org/uniprot/J3QL51|https://www.uniprot.org/uniprot/B5ME31|https://www.uniprot.org/uniprot/B4E3C2|https://www.uniprot.org/uniprot/B2R4H3
T646 1495-1499 Protein denotes PD‐1 https://www.uniprot.org/uniprot/Q7M4M5|https://www.uniprot.org/uniprot/Q6NZ54|https://www.uniprot.org/uniprot/Q3KQW2|https://www.uniprot.org/uniprot/P18621|https://www.uniprot.org/uniprot/J3QL51|https://www.uniprot.org/uniprot/B5ME31|https://www.uniprot.org/uniprot/B4E3C2|https://www.uniprot.org/uniprot/B2R4H3
T654 1727-1733 Protein denotes CTLA‐4 https://www.uniprot.org/uniprot/Q9XSI1|https://www.uniprot.org/uniprot/Q9UKN9|https://www.uniprot.org/uniprot/Q9TT02|https://www.uniprot.org/uniprot/Q9QZZ7|https://www.uniprot.org/uniprot/Q9MYX7|https://www.uniprot.org/uniprot/Q96P43|https://www.uniprot.org/uniprot/Q8WXJ1|https://www.uniprot.org/uniprot/Q5S005|https://www.uniprot.org/uniprot/Q53TD5|https://www.uniprot.org/uniprot/Q52MC1|https://www.uniprot.org/uniprot/Q0PP65|https://www.uniprot.org/uniprot/P42072|https://www.uniprot.org/uniprot/P16410|https://www.uniprot.org/uniprot/P09793|https://www.uniprot.org/uniprot/O95653|https://www.uniprot.org/uniprot/E9PDH0|https://www.uniprot.org/uniprot/A0N1S0
T671 2137-2141 Protein denotes PD‐1 https://www.uniprot.org/uniprot/Q7M4M5|https://www.uniprot.org/uniprot/Q6NZ54|https://www.uniprot.org/uniprot/Q3KQW2|https://www.uniprot.org/uniprot/P18621|https://www.uniprot.org/uniprot/J3QL51|https://www.uniprot.org/uniprot/B5ME31|https://www.uniprot.org/uniprot/B4E3C2|https://www.uniprot.org/uniprot/B2R4H3
T679 2452-2456 Protein denotes CD28 https://www.uniprot.org/uniprot/Q9BYV0|https://www.uniprot.org/uniprot/Q8WXJ2|https://www.uniprot.org/uniprot/Q8NI56|https://www.uniprot.org/uniprot/Q8NI55|https://www.uniprot.org/uniprot/Q8NI54|https://www.uniprot.org/uniprot/Q70WG0|https://www.uniprot.org/uniprot/Q6GSH7|https://www.uniprot.org/uniprot/Q52M23|https://www.uniprot.org/uniprot/Q28071|https://www.uniprot.org/uniprot/Q13964|https://www.uniprot.org/uniprot/P42069|https://www.uniprot.org/uniprot/P31042|https://www.uniprot.org/uniprot/P31041|https://www.uniprot.org/uniprot/P10747|https://www.uniprot.org/uniprot/O02757|https://www.uniprot.org/uniprot/A8KAC1
T695 2796-2801 Protein denotes PD‐L1 https://www.uniprot.org/uniprot/Q9NZQ7|https://www.uniprot.org/uniprot/Q9NUZ5|https://www.uniprot.org/uniprot/Q9EP73|https://www.uniprot.org/uniprot/Q6WEX4|https://www.uniprot.org/uniprot/Q66RK1|https://www.uniprot.org/uniprot/Q2V8D5|https://www.uniprot.org/uniprot/Q14CJ2|https://www.uniprot.org/uniprot/B4DU27|https://www.uniprot.org/uniprot/B2RBA2
T704 3609-3614 Protein denotes PD‐L1 https://www.uniprot.org/uniprot/Q9NZQ7|https://www.uniprot.org/uniprot/Q9NUZ5|https://www.uniprot.org/uniprot/Q9EP73|https://www.uniprot.org/uniprot/Q6WEX4|https://www.uniprot.org/uniprot/Q66RK1|https://www.uniprot.org/uniprot/Q2V8D5|https://www.uniprot.org/uniprot/Q14CJ2|https://www.uniprot.org/uniprot/B4DU27|https://www.uniprot.org/uniprot/B2RBA2
T713 3638-3648 Protein denotes interferon https://www.uniprot.org/uniprot/P51527|https://www.uniprot.org/uniprot/P51526
T715 4054-4058 Protein denotes PD‐1 https://www.uniprot.org/uniprot/Q7M4M5|https://www.uniprot.org/uniprot/Q6NZ54|https://www.uniprot.org/uniprot/Q3KQW2|https://www.uniprot.org/uniprot/P18621|https://www.uniprot.org/uniprot/J3QL51|https://www.uniprot.org/uniprot/B5ME31|https://www.uniprot.org/uniprot/B4E3C2|https://www.uniprot.org/uniprot/B2R4H3

LitCovid-sample-PD-FMA

Id Subject Object Predicate Lexical cue fma_id
T392 51-54 Body_part denotes IgG http://purl.org/sig/ont/fma/fma62872
T393 175-178 Body_part denotes IgG http://purl.org/sig/ont/fma/fma62872
T394 551-554 Body_part denotes IgG http://purl.org/sig/ont/fma/fma62872
T395 853-862 Body_part denotes backbones http://purl.org/sig/ont/fma/fma13478
T396 1009-1012 Body_part denotes IgG http://purl.org/sig/ont/fma/fma62872
T397 1151-1160 Body_part denotes backbones http://purl.org/sig/ont/fma/fma13478
T398 1432-1440 Body_part denotes backbone http://purl.org/sig/ont/fma/fma13478
T399 1734-1742 Body_part denotes antibody http://purl.org/sig/ont/fma/fma62871
T400 1764-1772 Body_part denotes backbone http://purl.org/sig/ont/fma/fma13478
T401 1815-1820 Body_part denotes cells http://purl.org/sig/ont/fma/fma68646
T402 2022-2032 Body_part denotes neutrophil http://purl.org/sig/ont/fma/fma62860
T403 2928-2938 Body_part denotes amino acid http://purl.org/sig/ont/fma/fma82739
T404 3075-3082 Body_part denotes leucine http://purl.org/sig/ont/fma/fma82757
T405 3150-3157 Body_part denotes alanine http://purl.org/sig/ont/fma/fma82749
T406 3387-3397 Body_part denotes amino acid http://purl.org/sig/ont/fma/fma82739
T407 3563-3574 Body_part denotes amino acids http://purl.org/sig/ont/fma/fma82739
T408 4059-4067 Body_part denotes antibody http://purl.org/sig/ont/fma/fma62871
T409 4489-4491 Body_part denotes Ig http://purl.org/sig/ont/fma/fma62871
T410 4768-4777 Body_part denotes backbones http://purl.org/sig/ont/fma/fma13478

LitCovid-sample-PD-GO-BP-0

Id Subject Object Predicate Lexical cue
T116 1657-1665 http://purl.obolibrary.org/obo/GO_0015297 denotes exchange
T117 1792-1796 http://purl.obolibrary.org/obo/GO_0001788 denotes ADCC
T118 2022-2043 http://purl.obolibrary.org/obo/GO_0042119 denotes neutrophil activation
T119 2048-2057 http://purl.obolibrary.org/obo/GO_0006915 denotes apoptosis
T120 2048-2057 http://purl.obolibrary.org/obo/GO_0097194 denotes apoptosis
T121 2880-2901 http://purl.obolibrary.org/obo/GO_0006956 denotes complement activation
T122 4492-4500 http://purl.obolibrary.org/obo/GO_0015297 denotes exchange
T123 4613-4634 http://purl.obolibrary.org/obo/GO_0006956 denotes complement activation

LitCovid-sample-PD-MONDO

Id Subject Object Predicate Lexical cue mondo_id
T42 1383-1388 Disease denotes tumor http://purl.obolibrary.org/obo/MONDO_0005070
T43 1530-1536 Disease denotes cancer http://purl.obolibrary.org/obo/MONDO_0004992

LitCovid-sample-PD-HP

Id Subject Object Predicate Lexical cue hp_id
T38 1383-1388 Phenotype denotes tumor http://purl.obolibrary.org/obo/HP_0002664
T39 1530-1536 Phenotype denotes cancer http://purl.obolibrary.org/obo/HP_0002664

LitCovid-sample-GO-BP

Id Subject Object Predicate Lexical cue
T116 1657-1665 http://purl.obolibrary.org/obo/GO_0015297 denotes exchange
T117 1792-1796 http://purl.obolibrary.org/obo/GO_0001788 denotes ADCC
T118 2022-2043 http://purl.obolibrary.org/obo/GO_0042119 denotes neutrophil activation
T119 2048-2057 http://purl.obolibrary.org/obo/GO_0097194 denotes apoptosis
T120 2048-2057 http://purl.obolibrary.org/obo/GO_0006915 denotes apoptosis
T121 2880-2901 http://purl.obolibrary.org/obo/GO_0006956 denotes complement activation
T122 4492-4500 http://purl.obolibrary.org/obo/GO_0015297 denotes exchange
T123 4613-4634 http://purl.obolibrary.org/obo/GO_0006956 denotes complement activation

LitCovid-PD-GO-BP

Id Subject Object Predicate Lexical cue
T116 1657-1665 http://purl.obolibrary.org/obo/GO_0015297 denotes exchange
T117 1792-1796 http://purl.obolibrary.org/obo/GO_0001788 denotes ADCC
T118 2022-2043 http://purl.obolibrary.org/obo/GO_0042119 denotes neutrophil activation
T119 2048-2057 http://purl.obolibrary.org/obo/GO_0097194 denotes apoptosis
T120 2048-2057 http://purl.obolibrary.org/obo/GO_0006915 denotes apoptosis
T121 2880-2901 http://purl.obolibrary.org/obo/GO_0006956 denotes complement activation
T122 4492-4500 http://purl.obolibrary.org/obo/GO_0015297 denotes exchange
T123 4613-4634 http://purl.obolibrary.org/obo/GO_0006956 denotes complement activation

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T282 0-54 Sentence denotes Attenuating and ablating FcγR‐related functions of IgG
T283 55-163 Sentence denotes There are circumstances where binding to FcγR is unnecessary or undesirable in the MOA of a therapeutic mAb.
T284 164-501 Sentence denotes Unmodified IgG irrespective of its subclass or intended therapeutic effect has the potential to engage an FcγR which may lead to suboptimal therapeutic performance or to unexpected and catastrophic consequences.57, 59 Clearly reducing or eliminating FcγR interactions, when they are not required for therapeutic effect, may be desirable.
T285 502-594 Sentence denotes Indeed, this had been addressed by the choice of IgG subclass or by modifying the Fc region.
T286 595-756 Sentence denotes Indeed, most efforts in Fc engineering mAbs that have translated to an approved drug have focused on the reduction or elimination of FcγR interactions (Table 4).
T287 757-1024 Sentence denotes One approach to minimize interactions with the activating FcγR has been the use of IgG4 or IgG2 backbones, which show a more restricted specificity for the activating FcγR and consequently have been traditionally, and simplistically, viewed as “inert” IgG subclasses.
T288 1025-1206 Sentence denotes Notwithstanding the unexpected, and FcγR‐dependent, severe adverse reaction induced by the IgG4 TGN1412 mAb, the IgG4 or IgG2 backbones have been successfully used in many settings.
T289 1207-1441 Sentence denotes Indeed, checkpoint inhibitors, such as mAbs targeting CTLA‐4 or the PD‐L1/PD‐1 interaction for the suppression of inhibitory signals that contribute to immune tolerance in the tumor microenvironment, are formatted on an IgG4 backbone.
T290 1442-1666 Sentence denotes Pembrolizumab, nivolumab and cemiplimab are all anti‐PD‐1 antibodies currently used for cancer therapy and have been formatted on an IgG4 backbone95, 96, 97 with a stabilized core hinge (S228P) to prevent half‐IgG4 exchange.
T291 1667-1823 Sentence denotes Similarly, the checkpoint inhibitor tremelimumab is an anti‐CTLA‐4 antibody formatted on an IgG2 backbone to avoid potential ADCC killing of target cells.98
T292 1824-1895 Sentence denotes However, the use of IgG2 and IgG4 as “inert” subclasses is problematic.
T293 1896-2291 Sentence denotes Both bind to the activating receptors FcγRIIa‐H131 and FcγRI, respectively (Table 2), and initiate effector functions such as neutrophil activation and apoptosis induction.75, 99 Interestingly, in experimental systems, cross‐linking of anti‐PD‐1 IgG4‐based mAb by FcγRI switched its activity from blocking to activatory.10 Moreover, IgG4 binds to FcγRIIb, which may scaffold the therapeutic mAb.
T294 2292-2609 Sentence denotes Although scaffolding may be beneficial in some contexts, for example, in immune agonism,43 it can be disastrous and unexpected in others as it was for the anti‐CD28 TGN1412 mAb.59 Thus, the IgG2 and IgG4 subclasses are not the optimum choice for “FcR‐inactive” mAbs, and so modifying the Fc is a more direct approach.
T295 2610-2904 Sentence denotes The complete removal of the heavy‐chain N‐linked glycan is well known to ablate all FcγR binding by dramatically altering the Fc conformation.36, 67, 101, 102 Atezolizumab, an IgG1 anti‐PD‐L1 checkpoint inhibitor mAb, utilizes this strategy and eliminates FcγR and also complement activation.13
T296 2905-3016 Sentence denotes Modification to the Fc amino acid sequence of the FcγR‐contact regions can also be used to reduce FcγR binding.
T297 3017-3172 Sentence denotes A widely used modification of IgG1 is the substitution of leucine 234 and 235 in the lower hinge sequence (L234 L235 G236 G237) with alanine (L234A L235A).
T298 3173-3341 Sentence denotes It is often referred to as the “LALA mutation” and effectively eliminates FcγR binding by more than 100 fold104, 105 and is used in teplizumab and spesolimab (Table 4).
T299 3342-3546 Sentence denotes A separate strategy has used combinations of amino acid residues from the FcγR‐binding regions of IgG2 and IgG4, which have restricted FcγR specificity, together with other binding‐inactivating mutations.
T300 3547-3725 Sentence denotes The lower hinge amino acids of the IgG1 mAbs durvalumab (anti‐PD‐L1) and anifrolumab (anti‐interferon‐α receptor; Table 4) were modified to mimic the lower hinge of IgG4 (L234F).
T301 3726-3943 Sentence denotes They additionally incorporated L235E in the lower hinge and P331S in the F/G loop of the CH2 domain to ablate FcγR binding by disrupting two major FcγR contact sites7 and also coincidently decreasing C1q activation.16
T302 3944-4039 Sentence denotes IgG4 mAbs have been similarly engineered to eliminate their interaction with FcγRI and FcγRIIb.
T303 4040-4314 Sentence denotes The IgG4 anti‐PD‐1 antibody tislelizumab has had its FcγR contact residues in the lower hinge E233, F234, L235 substituted with the equivalent residues of IgG2 P, V, A (E233P, F234V, L235A) as well as the additional D265A mutation which disrupts a major FcγR contact in CH2.
T304 4315-4532 Sentence denotes It also has substitutions in the core hinge S228P and the CH3 L309V and R409K to stabilize the H‐chain disulfides and CH3 interactions, respectively, thereby preventing half‐Ig exchange characteristic of natural IgG4.
T305 4533-4637 Sentence denotes Collectively, these modifications create a stable IgG4 with no FcγR binding nor complement activation.17
T306 4638-4900 Sentence denotes Thus, Fc engineering is an effective way to remove FcγR effector functions and may be preferable to using unmodified IgG2 or IgG4 backbones that have a more restricted repertoire of FcγR interactions but which are still able to induce certain effector functions.

LitCovid-PD-HP

Id Subject Object Predicate Lexical cue hp_id
T38 1383-1388 Phenotype denotes tumor http://purl.obolibrary.org/obo/HP_0002664
T39 1530-1536 Phenotype denotes cancer http://purl.obolibrary.org/obo/HP_0002664