IFNGR binding synthetic cytokines and methods of use
Provided herein are IFNGR binding molecules that bind to IFNGR1 and IFNGR2 and comprise an anti-IFNGR2 sdAb and an anti-IFNGR2 V H H antibody.
1. An IFNG receptor (IFNGR) binding molecule that specifically binds to IFNGR1 and IFNGR2,
wherein the binding molecule causes the multimerization of IFNGR1 and IFNGR2 when bound to IFNGR1 and IFNGR2,
wherein the binding molecule comprises a single-domain antibody (sdAb) that specifically binds to IFNGR1 (an anti-IFNGR1 sdAb) and a sdAb that specifically binds to IFNGR2 (an anti-IFNGR2 sdAb),
wherein the anti-IFNGR1 sdAb comprising a CDR1, a CDR2, and a CDR3 in a single row of the following table:
Name
CDR1
SEQ ID NO:
DR903
RIASDYTRG
25
DR904
SILSINTMG
26
DR905
RTFTGYAMG
27
DR906
STFSTYVMG
28
DR907
RTFSNYAMG
29
DR908
RTFTSLAMG
30
DR909
RTFGTSFGALSMG
31
DR910
RTFSSYAMA
32
DR911
RSFSTYAMA
33
DR912
RTFSSYAMA
34
DR913
RTFSSYAMG
35
DR914
RAFSNSAMA
36
DR915
RTLHNFAMA
37
DR916
RPRTTYAMG
38
DR917
RTFSGYNMG
39
DR918
LTDSTYGMA
40
DR919
RTLSTYAMG
41
DR920
RSFANYAMG
42
DR921
RTFTFSTHNMG
43
DR922
SITSINTMG
44
DR923
RTFMTYAMG
45
DR924
RTFSRYAMG
46
DR925
RTFSRYAMG
47
DR926
RTFSRYAMN
48
Name
CDR2
SEQ ID NO:
DR903
AIIRSVGDSYYADSVKG
49
DR904
AISSGGSTNYADSVKG
50
DR905
VITWSGATTYYSASVKG
51
DR906
AISRSGGTTTYADSVKG
52
DR907
AINWNIGSTYYADSVKG
53
DR908
AISRSGGSTDYADSVKG
54
DR909
AITRNTGRTFYADSVKD
55
DR910
AISILGGSADYEDSVQG
56
DR911
AITVGGGSTYYVDSVKG
57
DR912
AITVSGASTYYADSVKG
58
DR913
AISSWSGGSTYYADSVKG
59
DR914
AISRGGGSTDYADSVKG
60
DR915
AISKGGGSADYADSVKG
61
DR916
AISKAGGSTYVADSAKG
62
DR917
AIAWAGSRTYYTDSVKG
63
DR918
AISRAGGSADHADSVKG
64
DR919
AISWRSGNTYYADSVKG
65
DR920
AISRGGGSTWYADSVKG
66
DR921
GIMWTSRASYADSVKG
67
DR922
AITSGGSTNYADSVKG
68
DR923
AISWSSGSTYYADSVKG
69
DR924
TISRSGGTTSYANSVKG
70
DR925
AISIGGGSADYADTVKG
71
DR926
AISWSSGNTYVADSVKG
72
Name
CDR3
SEQ ID NO:
DR903
GGHLYYGSRWRYPASYDY
73
DR904
DRAYY
74
DR905
RIRDGVSPENPNEYGY
75
DR906
RAGPAIGRTANDYHS
76
DR907
VWPTGRLRVDSEYDY
77
DR908
RDYSTLQYYNEYEYSD
78
DR909
TNSYDDLRRSYAYNY
79
DR910
RRPAPSDSYWSSTSYAY
80
DR911
RDYRRRSYAPEAEQYDY
81
DR912
GGPGTIFPDYDY
82
DR913
GDYYSDYFKYDNEN
83
DR914
RYYSGRYYESLEYDY
84
DR915
NDLASYSDSSYTSTSRYDY
85
DR916
RAGFAAQIFEYDY
86
DR917
HDETYYRLDRVDLYTH
87
DR918
GRSYSSPYDYFNALAYSY
88
DR919
NEVATMSGPHDH
89
DR920
RSYSGSYTYSFGEYDY
90
DR921
AWYGNSGASYDY
91
DR922
DSMYF
92
DR923
SSIATMYGPNDY
93
DR924
RDGPAMGVFGSDYDY
94
DR925
RTPRPSSSYFTPQDYEY
95
DR926
TTIATMSDENTY
96,
and
wherein the anti-IFNGR2 sdAb comprising a CDR1, a CDR2, and a CDR3 in a single row of the following table:
Name
CDR1
SEQ ID NO:
DR927
RTFTSYAMN
97
DR928
RTFSNYRMG
98
DR929
RTFSSYAMG
99
DR930
RTFSSYAVA
100
DR931
RTFSTYAMG
101
DR932
RTFSYTTIG
102
DR933
GTISSLAMG
103
DR934
RSFANYAMG
104
DR935
RAFSTYALG
105
DR936
RTFSSVAMA
106
DR937
RTFRSYSMG
107
DR938
RPRTTYAMG
108
DR939
RTFGTYAMG
109
DR940
RTFSNYAMG
110
DR941
SIFRLNLMG
111
DR942
RTFTGYAMG
112
DR943
RTVGYGMA
113
DR944
RTFTFSTHNMG
114
DR945
RTFSGYNMG
115
DR946
PFTRYAMG
116
DR947
GSFGRYTMG
117
DR948
SIDSSYYVS
118
DR949
SILRFNVMS
119
DR950
LTTSSAALA
120
DR951
RTFGTSFGSLSMG
121
DR952
RTFSSLAMA
122
DR953
PTFSTYAMA
123
DR954
RTLHNFAMA
124
DR955
RTFSSYAMA
125
DR956
RTFSSLAMA
126
DR957
RTFSSYAMA
127
DR958
RTFSGYNMG
128
Name
CDR2
SEQ ID NO:
DR927
AISWSSGNTYVADSVKG
129
DR928
AISRGGGTTLYADSVKG
130
DR929
AISRGGGSTDYADSVKG
131
DR930
ALSRGGGSAYYTDSVKG
132
DR931
AISVNGGSTYYADSVTG
133
DR932
VISAGGGSRDYADALKG
134
DR933
AISWSGRSTYYVDSVKG
135
DR934
AISRGGGSTWYADSVKG
136
DR935
AISRGGGSTDYADSVKG
137
DR936
AISSGGGSTDYADSVKG
138
DR937
AISWYSGTTYYADPVKG
139
DR938
AISKAGGSTYVADSAKG
140
DR939
SIDRDGSMSYYADSVKG
141
DR940
AISWYSGNTYYADSVKG
142
DR941
HVGTTGNTAYADSVKG
143
DR942
VITWSGATTYYSASVKG
144
DR943
AITWSGTSTYYPDSVKG
145
DR944
GIMWTSRASYADSVKG
146
DR945
AIAWAGSRTYYTDSVKG
147
DR946
AISWSSGNTYYVDSVKG
148
DR947
VISWSGTNTYYADSVKG
149
DR948
AINWGDSRTAYADSVKG
150
DR949
VITSGGSTNYADSVKG
151
DR950
TITSGGGSTYYADSVKG
152
DR951
AISRNIGRTYYADSVKD
153
DR952
AISRSGGSTDYADSVKG
154
DR953
AITQSGRTTYYEDSVKG
155
DR954
AISKGGGSADYADSVKG
156
DR955
AISILGGSADYEDSVQG
157
DR956
ATTILGGSADYGDPVKG
158
DR957
AITVSGASTYYADSVKG
159
DR958
AINWIGGATYYADSVKG
160
Name
CDR3
SEQ ID NO:
DR927
TTIATMSDEYTY
161
DR928
GDFSTTWDEYNY
162
DR929
RAYSGRYYQFLEYDY
163
DR930
RNYDGTYYQENQYNY
164
DR931
RRPYPGSDFLTWASYDY
165
DR932
RRNTDTYTTTGDYDY
166
DR933
GEDGHSEYDY
167
DR934
RSYSGSYTYSFGEYDY
168
DR935
RSYSSSYYYSQYEYDY
169
DR936
RDYSSRRYYQSRYEYDL
170
DR937
NEIATMESSNDY
171
DR938
RAGFAAQIFEYDY
172
DR939
SRRAVISLQTVDY
173
DR940
NQIATMISVGDY
174
DR941
DRWGQFS
175
DR942
RIRDGVSPENPNEYGY
176
DR943
GSRRRVGVDVGGYDY
177
DR944
AWYGNSGASYDY
178
DR945
HDETYYRLDRVDLYTH
179
DR946
NEVATMSGPDDY
180
DR947
RETYYSHWDERMEYDY
181
DR948
RIGLGGPVVAAPTRYPY
182
DR949
DESGQYY
183
DR950
RFYSTTYYYREHEYSD
184
DR951
TNSYDDLRRSYAYDY
185
DR952
RDYSTLQYYNEYEYSD
186
DR953
RDLWSDSPDDWRIYSF
187
DR954
NDLASYSDSSYTSTSRYDY
188
DR955
RRPAPSDSYWSSTSYAY
189
DR956
RRPAPSDNYWSPASYAY
190
DR957
GGPGTIFPDYDY
191
DR958
YSEKFYSGKDYYTRDYDY
192.
2. The IFNGR binding molecule of claim 1 , wherein the anti-IFNGR1 sdAb is a VHH antibody and/or the anti-IFNGR2 sdAb is a V H H antibody.
3. The IFNGR binding molecule of claim 1 , wherein the anti-IFNGR1 sdAb and the anti-IFNGR2 sdAb are joined by a peptide linker.
4. The IFNGR binding molecule of claim 3 , wherein the peptide linker comprises between 1 and 50 amino acids.
5. The IFNGR binding molecule of claim 4 , wherein the peptide linker comprises a sequence of GGGS (SEQ ID NO:13).
6. The IFNGR binding molecule of claim 1 , wherein the binding molecule comprises the anti-IFNGR1 sdAb linked to the N-terminus of a linker and the anti-IFNGR2 sdAb linked to the C-terminus of the linker.
7. The IFNGR binding molecule of claim 1 , wherein the binding molecule comprises the anti-IFNGR2 sdAb linked to the N-terminus of a linker and the anti-IFNGR1 sdAb linked to the C-terminus of the linker.
8. The IFNGR binding molecule of claim 6 , wherein the anti-IFNGR1 sdAb comprises a sequence having at least 90% sequence identity to a sequence of the following table:
Name
Sequence
SEQ ID NO:
DR903
EVQLVESGGGLVQAGGSLRLSCAASGRIASDYTRGWFRQAPGKEREFVAAI
193
IRSVGDSYYADSVKGRFTISIDNAENTVYLQMNSLKPEDTAVYYCAVGGHL
YYGSRWRYPASYDYWGQGTQVTVSS
DR904
EVQLVESGGGLVQAGGSLRLSCEASESILSINTMGWFRQAPGKQRELVAAI
194
SSGGSTNYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCDADRAYY
KGQGTQVTVSS
DR905
EVQLVESGGGLVQAGGSLRLSCVASGRTFTGYAMGWFRQAPGKEREFVAVI
195
TWSGATTYYSASVKGRFTLSRDNAKNTVYLQMNSLKSEDTAVYYCAIRIRD
GVSPENPNEYGYWGQGTQVTVSS
DR906
EVQLVESGGGLVQAGGSLRLSCAASGSTFSTYVMGWFRQAPGKEREFVAAI
196
SRSGGTTTYADSVKGREDISRDNGKNTLFLQMNSLIPEDTAAYYCAARAGP
AIGRTANDYHSWGQGTLVTVSS
DR907
EVQLVESGGGLVQAGGSLRLSCAASGRTFSNYAMGWFRQAPGNEREFVAAI
197
NWNIGSTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCGAVWPT
GRLRVDSEYDYWGQGTQVTVSS
DR908
EVQLVESGGGLVQAGGSLRVTCAASGRTFTSLAMGWFRQAPGKEREFVAAI
198
SRSGGSTDYADSVKGRFFISRDNAKSTLYLQMSSLKPEDTAVYYCAARDYS
TLQYYNEYEYSDWGQGTQVTVSS
DR909
EVQLVESGGGLVQAGGSLRLSCAASGRTFGTSFGALSMGWFRQAPGKEREF
199
VAAITRNTGRTFYADSVKDRFTISRDNAKNTASLQMNSLEPEDTAVYICAA
TNSYDDLRRSYAYNYWGQGTQVTVSS
DR910
EVQLVESGGGLVQTGGSLRLSCAASGRTFSSYAMAWFRQAPGKEREFVAAI
200
SILGGSADYEDSVQGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCAARRPA
PSDSYWSSTSYAYWGQGTLVTVSS
DR911
EVQLVESGGALVQAGGSLRLSCTVSGRSFSTYAMAWFRRAPGKERELVSAI
201
TVGGGSTYYVDSVKGRFTISRENAKNTLYLQMNNLKPEDTAIYICAARDYR
RRSYAPEAEQYDYWGQGTQVTVSS
DR912
EVQLVESGGGLVQAGGSLRLSCAPSGRTFSSYAMAWFRQPPGKEREFVAAI
202
TVSGASTYYADSVKGRFTISRDNAKNSMYLQMNSLKPEDTAVYYCAAGGPG
TIFPDYDYWGQGTQVTVSS
DR913
EVQLVESGGGLVQAGGFLRLSCAASGRTFSSYAMGWFRQIPGKERELVAAI
203
SSWSGGSTYYADSVKGRFTISRDNAKNTVYLQMLSLKPEDTAVYYCTTGDY
YSDYFKYDNENWGKGTQVTVSS
DR914
EVQLVESGGGLVQAGGSLTLSCVASGRAFSNSAMAWFRQTPGKEREFVSAI
204
SRGGGSTDYADSVKGRFTISKDNAKNTVYLQMNSLKPEDTAVYYCAMRYYS
GRYYESLEYDYWGQGTQVTVSS
DR915
EVQLVESGGGLVQAGGSLRLSCAAARRTLHNFAMAWFRQAPGKEREFVAAI
205
SKGGGSADYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAANDLA
SYSDSSYTSTSRYDYWGQGTQVTVSS
DR916
EVQLVESGGGLVQPGGSLRLSCTASGRPRTTYAMGWFRQAPGKEREIVAAI
206
SKAGGSTYVADSAKGRFAISKDNAKNTVYLQMNSLKPEDTAVYYCAARAGF
AAQIFEYDYWGQGTLVTVSS
DR917
EVQLVESGGGLVQAGGSLRLSCAASGRTFSGYNMGWFRQAPGKEREFVAAI
207
AWAGSRTYYTDSVKGRFTISRDNAKNTMYLQMNTLRPEDTAVYYCAAHDET
YYRLDRVDLYTHWGQGTLVTVSS
DR918
EVQLVESGGGLVQAGGSLRLSCATSGLTDSTYGMAWFRQAPGKEREFVAAI
208
SRAGGSADHADSVKGRFTVSRDNAKKMVYLQMNSLKPEDTAVYYCASGRSY
SSPYDYFNALAYSYWGQGTQVTVSS
DR919
EVQLVESGGGLVQPGGFLRLSCAASRRTLSTYAMGWFRQAPGKEREFVAAI
209
SWRSGNTYYADSVKGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCAANEVA
TMSGPHDHWGQGTLVTVSS
DR920
EVQLVESGGGLVQAGGSLRLSCAASGRSFANYAMGWFRQAPGKERETVAAI
210
SRGGGSTWYADSVKGRFTISKDNAKNTVYLQMNSLKPEDTAIYYCAARSYS
GSYTYSFGEYDYWGQGTQVTVSS
DR921
QVQLVESGGGLVQAGDSLRLSCAASGRTFTFSTHNMGWFRQAPGKEREFVG
211
GIMWTSRASYADSVKGRFTVSRDNAKNTVYLQMNSLKPEDTAVYYCAAAWY
GNSGASYDYWGQGTQVTVSS
DR922
QVQLVESGGGLVRAGGSLRLSCAASGSITSINTMGWFRQAPGKQRELVAAI
212
TSGGSTNYADSVKGRFTISRDNARNTVYLQMYSLKPEDTAVYYCEADSMYF
RGQGTQVTVSS
DR923
QVQLVESGGGLVQAGGSLRLSCAASRRTFMTYAMGWFRQAPGKEREFVAAI
213
SWSSGSTYYADSVKGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCTASSIA
TMYGPNDYAGQGTLVTVSS
DR924
QVQLVESGGGLVQAGGSLRLSCTASGRTFSRYAMGWFRQAPGKEREFVATI
214
SRSGGTTSYANSVKGRFTISRDNAKNTVYLQMNSLKTEDTAVYNCAARDGP
AMGVFGSDYDYWGQGTLVTVSS
DR925
EVQLVESGGGLVQAGGSLVLSCAASGRTFSRYAMGWFRQAPGKEREFVAAI
215
SIGGGSADYADTVKGRFTISRNNAKNTMYLQMNSLKPEDTAVYYCAARTPR
PSSSYFTPQDYEYWGQGTLVTVSS
DR926
EVQLVESGGGLVQAGGSLRLSCAASGRTFSRYAMNWFRQAPGKEREFVAAI
216
SWSSGNTYVADSVKGRFTISRDNAKNTMYLQMNNLAPEDTAVYYCAATTIA
TMSDENTYWGQGTQVTVSS.
9. The IFNGR binding molecule of claim 8 , wherein the anti-IFNGR1 sdAb comprises a sequence of the table in claim 8 .
10. The IFNGR binding molecule of claim 6 , wherein the anti-IFNGR2 g comprises a sequence having at least 90% sequence identity to a sequence of the following table:
Name
Sequence
SEQ ID NO:
DR927
QVQLVESGGGLVQAGGSLRLSCAASGRTFTSYAMNWFRQAPGKEREFVAAISWS
217
SGNTYVADSVKGRFAISRDKAKNTMYLQMNSLAPEDTAVYYCAATTIATMSDEY
TYWGQGTQVTVSS
DR928
QVQLVESGGGLVQAGGSLRLSCAASGRTFSNYRMGWFRQAPGKEREFVAAISRG
218
GGTTLYADSVKGRFTISRDNAKNTVDLQMNRLKPEDTAVYFCAAGDESTTWDEY
NYWGQGTQVTVSS
DR929
QVQLVESGGGLVQAGGSLRLSCVASGRTFSSYAMGWFRQTPGKEREFVSAISRG
219
GGSTDYADSVKGRFTISRDNAKNTVYLQMNNLKSEDTAVYYCALRAYSGRYYQF
LEYDYWGQGTQVTVSS
DR930
EVQLVESGGGLVQAGGSLRLSCTVSGRTFSSYAVAWFRQAPGNVRELAAALSRG
220
GGSAYYTDSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAARNYDGTYYQE
NQYNYWGQGTQVTVSS
DR931
QVQLVESGGGLVQAGGSLLLSCAASGRTFSTYAMGWFRQAPGKERMFVAAISVN
221
GGSTYYADSVTGRFTISRDNAKNTMYLQMNNLKPGDTAVYYCAARRPYPGSDFL
TWASYDYRGQGTLVTVSS
DR932
QVQLVESGGGLVQAGGFLRLSCAASGRTFSYTTIGWFRQAPGKEREFVAVISAG
222
GGSRDYADALKGRFTISRDNAKKMVYLQMNNLKPEDTAVYYCAVRRNTDTYTTT
GDYDYWGQGTQVTVSS
DR933
QVQLVESGGGLVQPGDSLRLSCVASGGTISSLAMGWFRQAPGKEREFVAAISWS
223
GRSTYYVDSVKGRFTISTDNAKNTVYLQMNSLKPEDTAVYYCVAGEDGHSEYDY
WGQGTQVTVSS
DR934
QVQLVESGGGLVQAGGSLRLSCAASGRSFANYAMGWFRQAPGKERETVAAISRG
224
GGSTWYADSVKGRFTISKDNAKNTVYLQMNSLKPEDTAIYYCAARSYSGSYTYS
FGEYDYWGQGTQVTVSS
DR935
QVQLVESGGGLVQAGGSLRLSCAASGRAFSTYALGWFRQAPGKEREFIAAISRG
225
GGSTDYADSVKGRFTISRDNAKSTVYLQMNSLKPEDTAVYYCAARSYSSSYYYS
QYEYDYWGQGTQVTVSS
DR936
EVQLVESGGGLVQAGGSLRLSCAASGRTFSSVAMAWFRQAPGKEREFVSAISSG
226
GGSTDYADSVKGRFTISKDNAKNTMYLQMDSLKPEDTAVYYCAARDYSSRRYYQ
SRYEYDLWGLGTQVTVSS
DR937
QVQLVESGGGLVQPGGSLRLSCAASGRTFRSYSMGWFRQAPGKEREFVAAISWY
227
SGTTYYADPVKGRFTISRDDAKNTLYLQMNSLKPEDTAVYYCAANEIATMESSN
DYWGQGTQVTVSS
DR938
QVQLVESGGGLVQPGGSLRLSCTASGRPRTTYAMGWFRQAPGKEREIVAAISKA
228
GGSTYVADSAKGRFAISKDNAKNTVYLQMNSLKPEDTAVYYCAARAGFAAQIFE
YDYWGQGTLVTVSS
DR939
EVQLVESGGGLVQAGGSMRLSCANSGRTFGTYAMGWFRQSPGKERERVASIDRD
229
GSMSYYADSVKGRFTISGDNAKNTVYLQMNSLKPEDTAVYYCAASRRAVISLQT
VDYWGQGTQVTVSS
DR940
EVQLVESGGRLVQTGGSLRLSCAASGRTFSNYAMGWFRQAPGKEREFVAAISWY
230
SGNTYYADSVKGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCAANQIATMISVG
DYWGQGTLVTVSS
DR941
QVQLVESGGGLVEAGGSLRLACAASGSIFRLNLMGWYRQAPGKQRELVAHVGTT
231
GNTAYADSVKGRFTISKDDAKNMVFLQMNSLKPEDTAVYYCYADRWGQFSWGQG
TQVTVSS
DR942
QVQLVESGGGLVQAGGSLRLSCVASGRTFTGYAMGWFRQAPGKEREFVAVITWS
232
GATTYYSASVKGRFTLSRDNAKNTVYLQMNSLKSEDTAVYYCAIRIRDGVSPEN
PNEYGYWGQGTQVTVSS
DR943
QVQLVESGGGLVQAGGSLRLSCVASGRTVGYGMAWFRQAPGKQRDVVAAITWSG
233
TSTYYPDSVKGRFTISRDNAKNTMYLQMSSLKPEDTAVYYCAAGSRRRVGVDVG
GYDYWGQGTQVTVSS
DR944
QVQLVESGGGLVQAGDSLRLSCAASGRTFTFSTHNMGWFRQAPGKEREFVGGIM
234
WTSRASYADSVKGRFTVSRDNAKNTVYLQMNSLKPEDTAVYYCAAAWYGNSGAS
YDYWGQGTQVTVSS
DR945
QVQLVESGGGLVQLVQAGGSLRLSCAASGRTFSGYNMGWFRQAPGKEREFVAAI
235
AWAGSRTYYTDSVKGRFTISRDNAKNTMYLQMNTLRPEDTAVYYCAAHDETYYR
LDRVDLYTHWGQGTQVTVSS
DR946
QVQLVESGGGLVQPGESLRLSCAASGPFTRYAMGWFRQAPGKEREFVAAISWSS
236
GNTYYVDSVKGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCAANEVATMSGPDD
YWGQGTQVTVSS
DR947
QVQLVESGGGLVQAGGSLRLSCAASGGSFGRYTMGWYRQAPGKEREFVAVISWS
237
GTNTYYADSVKGRFTISRDNAKNTMYLQMNDLKPEDTAVYYCAARETYYSHWDE
RMEYDYWGQGTQVTVSS
DR948
QVQLVESGGGLVQAGDSLRLSCVASGSIDSSYYVSWFRQAPGKERDLVAAINWG
238
DSRTAYADSVKGRFTISRDNAKNTVYLQMHSLRPNDTAVYYCASRIGLGGPVVA
APTRYPYWGQGTLVTVSS
DR949
QVQLVESGGGLVQAGGSLRLSCAASESILRFNVMSWLRQAPGKQRELVAVITSG
239
GSTNYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAADESGQYYWGQG
TQVTVSS
DR950
QVQLVESGGGLVQAGGSLRLSCAASGLTTSSAALAWFRQAPGKERELDPTITSG
240
GGSTYYADSVKGRFTISKDNAKNTLYLQMSSLKPEDTAVYYCAARFYSTTYYYR
EHEYSDWGQGTQVTVSS
DR951
QVQLVESGGGLVQAGGSLRLSCAASGRTFGTSFGSLSMGWFRQAPGKEREFVAA
241
ISRNIGRTYYADSVKDRFTISRDNAKNTASLQMNSLEPEDTAVYNCAATNSYDD
LRRSYAYDYWGQGTQVTVSS
DR952
QVQLVESGGGLVQAGGFLRLSCAASGRTFSSLAMAWFRQAPGKEREFVAAISRS
242
GGSTDYADSVKGRFTISRDNAKSTLYLQMSSLKPEDTAVYYCAARDYSTLQYYN
EYEYSDWGQGTLVTVSS
DR953
QVQLVESGGGLVQAGDSLRLSCAASGPTFSTYAMAWFRQAPGKEREFVAAITQS
243
GRTTYYEDSVKGRFTISKDNAKNTLYLQMNSLQPEDTAVYYCAARDLWSDSPDD
WRIYSFWGQGTQVTVSS
DR954
QVQLVESGGGLVQAGGSLRLSCAAARRTLHNFAMAWFRQAPGKEREFVAAISKG
244
GGSADYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAANDLASYSDSS
YTSTSRYDYWGQGTQVTVSS
DR955
QVQLVESGGGLVQTGGSLRLSCAASGRTFSSYAMAWFRQAPGKEREFVAAISIL
245
GGSADYEDSVQGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCAARRPAPSDSYW
SSTSYAYWGQGTLVTVSS
DR956
EVQLVESGGGLVQAGGSLRLSCAASGRTFSSLAMAWFRQAPGKEREFVAATTIL
246
GGSADYGDPVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCTGRRPAPSDNYW
SPASYAYWGQGTQVTVSS
DR957
QVQLVESGGGLVQAGGSLRLSCAPSGRTFSSYAMAWFRQPPGKEREFVAAITVS
247
GASTYYADSVKGRFTISRDNAKNSMYLQMNSLKPEDTAVYYCAAGGPGTIFPDY
DYWGQGTQVTVSS
DR958
QVQLVESGGGLVQAGDSLTLSCTASGRTFSGYNMGWFRQAPGKERDFVAAINWI
248
GGATYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCHRYSEKFYSGKD
YYTRDYDYWGQGTQVTVSS.
11. The IFNGR binding molecule of claim 10 , wherein the anti-IFNGR2 sdAb comprises a sequence of the table in claim 10 .
12. The IFNGR binding molecule of claim 6 , wherein each of the anti-IFNGR1 sdAb comprises a sequence having at least 90% sequence identity to a sequence of the following table:
Name
Sequence
SEQ ID NO:
DR903
EVQLVESGGGLVQAGGSLRLSCAASGRIASDYTRGWFRQAPGKEREFVAAI
193
IRSVGDSYYADSVKGRFTISIDNAENTVYLQMNSLKPEDTAVYYCAVGGHL
YYGSRWRYPASYDYWGQGTQVTVSS
DR904
EVQLVESGGGLVQAGGSLRLSCEASESILSINTMGWFRQAPGKQRELVAAI
194
SSGGSTNYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCDADRAYY
KGQGTQVTVSS
DR905
EVQLVESGGGLVQAGGSLRLSCVASGRTFTGYAMGWFRQAPGKEREFVAVI
195
TWSGATTYYSASVKGRFTLSRDNAKNTVYLQMNSLKSEDTAVYYCAIRIRD
GVSPENPNEYGYWGQGTQVTVSS
DR906
EVQLVESGGGLVQAGGSLRLSCAASGSTFSTYVMGWFRQAPGKEREFVAAI
196
SRSGGTTTYADSVKGRFDISRDNGKNTLFLQMNSLIPEDTAAYYCAARAGP
AIGRTANDYHSWGQGTLVTVSS
DR907
EVQLVESGGGLVQAGGSLRLSCAASGRTFSNYAMGWFRQAPGNEREFVAAI
197
NWNIGSTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCGAVWPT
GRLRVDSEYDYWGQGTQVTVSS
DR908
EVQLVESGGGLVQAGGSLRVTCAASGRTFTSLAMGWFRQAPGKEREFVAAI
198
SRSGGSTDYADSVKGRFFISRDNAKSTLYLQMSSLKPEDTAVYYCAARDYS
TLQYYNEYEYSDWGQGTQVTVSS
DR909
EVQLVESGGGLVQAGGSLRLSCAASGRTFGTSFGALSMGWFRQAPGKEREF
199
VAAITRNTGRTFYADSVKDRFTISRDNAKNTASLQMNSLEPEDTAVYICAA
TNSYDDLRRSYAYNYWGQGTQVTVSS
DR910
EVQLVESGGGLVQTGGSLRLSCAASGRTFSSYAMAWFRQAPGKEREFVAAI
200
SILGGSADYEDSVQGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCAARRPA
PSDSYWSSTSYAYWGQGTLVTVSS
DR911
EVQLVESGGALVQAGGSLRLSCTVSGRSFSTYAMAWFRRAPGKERELVSAI
201
TVGGGSTYYVDSVKGRFTISRENAKNTLYLQMNNLKPEDTAIYICAARDYR
RRSYAPEAEQYDYWGQGTQVTVSS
DR912
EVQLVESGGGLVQAGGSLRLSCAPSGRTFSSYAMAWFRQPPGKEREFVAAI
202
TVSGASTYYADSVKGRFTISRDNAKNSMYLQMNSLKPEDTAVYYCAAGGPG
TIFPDYDYWGQGTQVTVSS
DR913
EVQLVESGGGLVQAGGFLRLSCAASGRTESSYAMGWFRQIPGKERELVAAI
203
SSWSGGSTYYADSVKGRFTISRDNAKNTVYLQMLSLKPEDTAVYYCTTGDY
YSDYFKYDNENWGKGTQVTVSS
DR914
EVQLVESGGGLVQAGGSLTLSCVASGRAFSNSAMAWFRQTPGKEREFVSAI
204
SRGGGSTDYADSVKGRFTISKDNAKNTVYLQMNSLKPEDTAVYYCAMRYYS
GRYYESLEYDYWGQGTQVTVSS
DR915
EVQLVESGGGLVQAGGSLRLSCAAARRTLHNFAMAWFRQAPGKEREFVAAI
205
SKGGGSADYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAANDLA
SYSDSSYTSTSRYDYWGQGTQVTVSS
DR916
EVQLVESGGGLVQPGGSLRLSCTASGRPRTTYAMGWFRQAPGKEREIVAAI
206
SKAGGSTYVADSAKGRFAISKDNAKNTVYLQMNSLKPEDTAVYYCAARAGF
AAQIFEYDYWGQGTLVTVSS
DR917
EVQLVESGGGLVQAGGSLRLSCAASGRTFSGYNMGWFRQAPGKEREFVAAI
207
AWAGSRTYYTDSVKGRFTISRDNAKNTMYLQMNTLRPEDTAVYYCAAHDET
YYRLDRVDLYTHWGQGTLVTVSS
DR918
EVQLVESGGGLVQAGGSLRLSCATSGLTDSTYGMAWFRQAPGKEREFVAAI
208
SRAGGSADHADSVKGRFTVSRDNAKKMVYLQMNSLKPEDTAVYYCASGRSY
SSPYDYFNALAYSYWGQGTQVTVSS
DR919
EVQLVESGGGLVQPGGFLRLSCAASRRTLSTYAMGWFRQAPGKEREFVAAI
209
SWRSGNTYYADSVKGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCAANEVA
TMSGPHDHWGQGTLVTVSS
DR920
EVQLVESGGGLVQAGGSLRLSCAASGRSFANYAMGWFRQAPGKERETVAAI
210
SRGGGSTWYADSVKGRFTISKDNAKNTVYLQMNSLKPEDTAIYYCAARSYS
GSYTYSFGEYDYWGQGTQVTVSS
DR921
QVQLVESGGGLVQAGDSLRLSCAASGRTFTFSTHNMGWFRQAPGKEREFVG
211
GIMWTSRASYADSVKGRFTVSRDNAKNTVYLQMNSLKPEDTAVYYCAAAWY
GNSGASYDYWGQGTQVTVSS
DR922
QVQLVESGGGLVRAGGSLRLSCAASGSITSINTMGWFRQAPGKQRELVAAI
212
TSGGSTNYADSVKGRFTISRDNARNTVYLQMYSLKPEDTAVYYCEADSMYF
RGQGTQVTVSS
DR923
QVQLVESGGGLVQAGGSLRLSCAASRRTFMTYAMGWFRQAPGKEREFVAAI
213
SWSSGSTYYADSVKGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCTASSIA
TMYGPNDYAGQGTLVTVSS
DR924
QVQLVESGGGLVQAGGSLRLSCTASGRTFSRYAMGWFRQAPGKEREFVATI
214
SRSGGTTSYANSVKGRFTISRDNAKNTVYLQMNSLKTEDTAVYNCAARDGP
AMGVFGSDYDYWGQGTLVTVSS
DR925
EVQLVESGGGLVQAGGSLVLSCAASGRTFSRYAMGWFRQAPGKEREFVAAI
215
SIGGGSADYADTVKGRFTISRNNAKNTMYLQMNSLKPEDTAVYYCAARTPR
PSSSYFTPQDYEYWGQGTLVTVSS
DR926
EVQLVESGGGLVQAGGSLRLSCAASGRTFSRYAMNWFRQAPGKEREFVAAI
216
SWSSGNTYVADSVKGRFTISRDNAKNTMYLQMNNLAPEDTAVYYCAATTIA
TMSDENTYWGQGTQVTVSS,
and the anti-IFNGR2 sdAb comprises a sequence having at least 90% sequence identity to a sequence of the following table:
Name
Sequence
SEQ ID NO:
DR927
QVQLVESGGGLVQAGGSLRLSCAASGRTFTSYAMNWFRQAPGKEREFVAAISWS
217
SGNTYVADSVKGRFAISRDKAKNTMYLQMNSLAPEDTAVYYCAATTIATMSDEY
TYWGQGTQVTVSS
DR928
QVQLVESGGGLVQAGGSLRLSCAASGRTFSNYRMGWFRQAPGKEREFVAAISRG
218
GGTTLYADSVKGRFTISRDNAKNTVDLQMNRLKPEDTAVYFCAAGDESTTWDEY
NYWGQGTQVTVSS
DR929
QVQLVESGGGLVQAGGSLRLSCVASGRTFSSYAMGWFRQTPGKEREFVSAISRG
219
GGSTDYADSVKGRFTISRDNAKNTVYLQMNNLKSEDTAVYYCALRAYSGRYYQF
LEYDYWGQGTQVTVSS
DR930
EVQLVESGGGLVQAGGSLRLSCTVSGRTFSSYAVAWFRQAPGNVRELAAALSRG
220
GGSAYYTDSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAARNYDGTYYQE
NQYNYWGQGTQVTVSS
DR931
QVQLVESGGGLVQAGGSLLLSCAASGRTFSTYAMGWFRQAPGKERMFVAAISVN
221
GGSTYYADSVTGRFTISRDNAKNTMYLQMNNLKPGDTAVYYCAARRPYPGSDFL
TWASYDYRGQGTLVTVSS
DR932
QVQLVESGGGLVQAGGFLRLSCAASGRTFSYTTIGWFRQAPGKEREFVAVISAG
222
GGSRDYADALKGRFTISRDNAKKMVYLQMNNLKPEDTAVYYCAVRRNTDTYTTT
GDYDYWGQGTQVTVSS
DR933
QVQLVESGGGLVQPGDSLRLSCVASGGTISSLAMGWFRQAPGKEREFVAAISWS
223
GRSTYYVDSVKGRFTISTDNAKNTVYLQMNSLKPEDTAVYYCVAGEDGHSEYDY
WGQGTQVTVSS
DR934
QVQLVESGGGLVQAGGSLRLSCAASGRSFANYAMGWFRQAPGKERETVAAISRG
224
GGSTWYADSVKGRFTISKDNAKNTVYLQMNSLKPEDTAIYYCAARSYSGSYTYS
FGEYDYWGQGTQVTVSS
DR935
QVQLVESGGGLVQAGGSLRLSCAASGRAFSTYALGWFRQAPGKEREFIAAISRG
225
GGSTDYADSVKGRETISRDNAKSTVYLQMNSLKPEDTAVYYCAARSYSSSYYYS
QYEYDYWGQGTQVTVSS
DR936
EVQLVESGGGLVQAGGSLRLSCAASGRTFSSVAMAWFRQAPGKEREFVSAISSG
226
GGSTDYADSVKGRFTISKDNAKNTMYLQMDSLKPEDTAVYYCAARDYSSRRYYQ
SRYEYDLWGLGTQVTVSS
DR937
QVQLVESGGGLVQPGGSLRLSCAASGRTFRSYSMGWFRQAPGKEREFVAAISWY
227
SGTTYYADPVKGRFTISRDDAKNTLYLQMNSLKPEDTAVYYCAANEIATMESSN
DYWGQGTQVTVSS
DR938
QVQLVESGGGLVQPGGSLRLSCTASGRPRTTYAMGWFRQAPGKEREIVAAISKA
228
GGSTYVADSAKGRFAISKDNAKNTVYLQMNSLKPEDTAVYYCAARAGFAAQIFE
YDYWGQGTLVTVSS
DR939
EVQLVESGGGLVQAGGSMRLSCANSGRTFGTYAMGWFRQSPGKERERVASIDRD
229
GSMSYYADSVKGRFTISGDNAKNTVYLQMNSLKPEDTAVYYCAASRRAVISLQT
VDYWGQGTQVTVSS
DR940
EVQLVESGGRLVQTGGSLRLSCAASGRTFSNYAMGWFRQAPGKEREFVAAISWY
230
SGNTYYADSVKGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCAANQIATMISVG
DYWGQGTLVTVSS
DR941
QVQLVESGGGLVEAGGSLRLACAASGSIFRLNLMGWYRQAPGKQRELVAHVGTT
231
GNTAYADSVKGRFTISKDDAKNMVFLQMNSLKPEDTAVYYCYADRWGQFSWGQG
TQVTVSS
DR942
QVQLVESGGGLVQAGGSLRLSCVASGRTFTGYAMGWFRQAPGKEREFVAVITWS
232
GATTYYSASVKGRFTLSRDNAKNTVYLQMNSLKSEDTAVYYCAIRIRDGVSPEN
PNEYGYWGQGTQVTVSS
DR943
QVQLVESGGGLVQAGGSLRLSCVASGRTVGYGMAWFRQAPGKQRDVVAAITWSG
233
TSTYYPDSVKGRFTISRDNAKNTMYLQMSSLKPEDTAVYYCAAGSRRRVGVDVG
GYDYWGQGTQVTVSS
DR944
QVQLVESGGGLVQAGDSLRLSCAASGRTFTFSTHNMGWFRQAPGKEREFVGGIM
234
WTSRASYADSVKGRFTVSRDNAKNTVYLQMNSLKPEDTAVYYCAAAWYGNSGAS
YDYWGQGTQVTVSS
DR945
QVQLVESGGGLVQLVQAGGSLRLSCAASGRTFSGYNMGWFRQAPGKEREFVAAI
235
AWAGSRTYYTDSVKGRFTISRDNAKNTMYLQMNTLRPEDTAVYYCAAHDETYYR
LDRVDLYTHWGQGTQVTVSS
DR946
QVQLVESGGGLVQPGESLRLSCAASGPFTRYAMGWFRQAPGKEREFVAAISWSS
236
GNTYYVDSVKGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCAANEVATMSGPDD
YWGQGTQVTVSS
DR947
QVQLVESGGGLVQAGGSLRLSCAASGGSFGRYTMGWYRQAPGKEREFVAVISWS
237
GTNTYYADSVKGRFTISRDNAKNTMYLQMNDLKPEDTAVYYCAARETYYSHWDE
RMEYDYWGQGTQVTVSS
DR948
QVQLVESGGGLVQAGDSLRLSCVASGSIDSSYYVSWFRQAPGKERDLVAAINWG
238
DSRTAYADSVKGRFTISRDNAKNTVYLQMHSLRPNDTAVYYCASRIGLGGPVVA
APTRYPYWGQGTLVTVSS
DR949
QVQLVESGGGLVQAGGSLRLSCAASESILRFNVMSWLRQAPGKQRELVAVITSG
239
GSTNYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAADESGQYYWGQG
TQVTVSS
DR950
QVQLVESGGGLVQAGGSLRLSCAASGLTTSSAALAWFRQAPGKERELDPTITSG
240
GGSTYYADSVKGRFTISKDNAKNTLYLQMSSLKPEDTAVYYCAARFYSTTYYYR
EHEYSDWGQGTQVTVSS
DR951
QVQLVESGGGLVQAGGSLRLSCAASGRTFGTSFGSLSMGWFRQAPGKEREFVAA
241
ISRNIGRTYYADSVKDRFTISRDNAKNTASLQMNSLEPEDTAVYNCAATNSYDD
LRRSYAYDYWGQGTQVTVSS
DR952
QVQLVESGGGLVQAGGFLRLSCAASGRTFSSLAMAWFRQAPGKEREFVAAISRS
242
GGSTDYADSVKGRFTISRDNAKSTLYLQMSSLKPEDTAVYYCAARDYSTLQYYN
EYEYSDWGQGTLVTVSS
DR953
QVQLVESGGGLVQAGDSLRLSCAASGPTFSTYAMAWFRQAPGKEREFVAAITQS
243
GRTTYYEDSVKGRFTISKDNAKNTLYLQMNSLQPEDTAVYYCAARDLWSDSPDD
WRIYSFWGQGTQVTVSS
DR954
QVQLVESGGGLVQAGGSLRLSCAAARRTLHNFAMAWFRQAPGKEREFVAAISKG
244
GGSADYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAANDLASYSDSS
YTSTSRYDYWGQGTQVTVSS
DR955
QVQLVESGGGLVQTGGSLRLSCAASGRTFSSYAMAWFRQAPGKEREFVAAISIL
245
GGSADYEDSVQGRFTISRDNAKNTMYLQMNSLKPEDTAVYYCAARRPAPSDSYW
SSTSYAYWGQGTLVTVSS
DR956
EVQLVESGGGLVQAGGSLRLSCAASGRTFSSLAMAWFRQAPGKEREFVAATTIL
246
GGSADYGDPVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCTGRRPAPSDNYW
SPASYAYWGQGTQVTVSS
DR957
QVQLVESGGGLVQAGGSLRLSCAPSGRTFSSYAMAWFRQPPGKEREFVAAITVS
247
GASTYYADSVKGRFTISRDNAKNSMYLQMNSLKPEDTAVYYCAAGGPGTIFPDY
DYWGQGTQVTVSS
DR958
QVQLVESGGGLVQAGDSLTLSCTASGRTFSGYNMGWFRQAPGKERDFVAAINWI
248
GGATYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCHRYSEKFYSGKD
YYTRDYDYWGQGTQVTVSS.
13. The IFNGR binding molecule of claim 12 , wherein each of the anti-IFNGR1 sdAb comprises a sequence of the first table in claim 12 and the anti-IFNGR2 sdAb comprises a sequence of the second table in claim 12 .
14. A pharmaceutically acceptable formulation comprising the IFNGR binding molecule of claim 1 and a pharmaceutically acceptable carrier.