US 12,291,572 B2
IL12 receptor synthetic cytokines and methods of use
Robert Kastelein, Menlo Park, CA (US); Deepti Rokkam, Menlo Park, CA (US); and Patrick J. Lupardus, Menlo Park, CA (US)
Assigned to Synthekine, Inc., Menlo Park, CA (US)
Appl. No. 18/018,448
Filed by Synthekine, Inc., Menlo Park, CA (US)
PCT Filed Aug. 5, 2021, PCT No. PCT/US2021/044855
§ 371(c)(1), (2) Date Jan. 27, 2023,
PCT Pub. No. WO2022/032042, PCT Pub. Date Feb. 10, 2022.
Claims priority of provisional application 63/135,884, filed on Jan. 11, 2021.
Claims priority of provisional application 63/078,745, filed on Sep. 15, 2020.
Claims priority of provisional application 63/061,562, filed on Aug. 5, 2020.
Prior Publication US 2023/0279127 A1, Sep. 7, 2023
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61P 37/02 (2006.01); C07K 14/715 (2006.01); C07K 16/46 (2006.01); C07K 19/00 (2006.01); C12N 15/63 (2006.01); C12N 15/86 (2006.01)
CPC C07K 16/2866 (2013.01) [A61P 37/02 (2018.01); C07K 14/7155 (2013.01); C07K 16/2803 (2013.01); C07K 16/46 (2013.01); C07K 16/468 (2013.01); C07K 19/00 (2013.01); C12N 15/63 (2013.01); C12N 15/86 (2013.01); A61K 2039/505 (2013.01); C07K 2317/22 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/33 (2013.01); C07K 2317/522 (2013.01); C07K 2317/524 (2013.01); C07K 2317/526 (2013.01); C07K 2317/53 (2013.01); C07K 2317/565 (2013.01); C07K 2317/567 (2013.01); C07K 2317/569 (2013.01); C07K 2319/40 (2013.01)] 12 Claims
 
1. An IL12 receptor binding molecule that specifically binds to IL12Rb1 and IL12Rb2,
wherein the binding molecule comprises a single-domain antibody (sdAb) that specifically binds to IL12Rb1 (an anti-IL12Rb1 sdAb) and a sdAb that specifically binds to IL12Rb2 (an anti-IL12Rb2 sdAb),
wherein the anti-IL12Rb1 sdAb and the anti-IL12Rb2 sdAb are joined by a peptide linker that comprises between 1 and 50 amino acids or a covalent bond, or
wherein the C-terminus of the anti-IL12Rb1 sdAb is conjugated to a first Fc monomer of an Fc domain and the C-terminus of the anti-IL12Rb2 sdAb is conjugated to a second Fc monomer of the Fc domain, and wherein one of the first and second Fc monomers comprises a knob and the other of the first and second Fc monomers comprises a hole, and wherein the knob and the hole form a knob-into-hole interface and non-covalently associate with each other,
wherein the anti-IL12Rb1 sdAb comprises a CDR1, a CDR2, and a CDR3 in a single row of the following table:
 
 
 
 
 SEQ
 
 
 
 ID
 
 Name CDR1 NO:
 
 
 hIL12Rb1_VHH1 YGYCGYDMS 25
 
 
 hIL12Rb1_VHH2 YTYSSAFMA 26
 
 
 hIL12Rb1_VHH3 YSYCGYDMM 27
 
 
 hIL12Rb1_VHH4 YGYCGYDMS 28
 
 
 hIL12Rb1_VHH5 YGYCGYDMS 29
 
 
 hIL12Rb1_VHH6 YTYTNNFMA 30
 
 
 hIL12Rb1_VHH7 YDYCGYDVR 31
 
 
 hIL12Rb1_VHH8 YSYCGYDMM 32
 
 
 hIL12Rb1_VHH9 YSYCGYDMM 33
 
 
 hIL12Rb1_VHH10 YDYCGYDVR 34
 
 
 hIL12Rb1_VHH11 YDYCGYDVR 35
 
 
 hIL12Rb1_VHH12 YTYSSAFMA 36
 
 
 hIL12Rb1_VHH13 YGYCGYDMS 37
 
 
 hIL12Rb1_VHH14 YDYCGYDVR 38
 
 
 hIL12Rb1_VHH15 YDYCGYDVR 39
 
 
 hIL12Rb1_VHH16 YTYSSAFMA 40
 
 
 hIL12Rb1_VHH17 YGYCGYDMS 41
 
 
 hIL12Rb1_VHH18 YTYTNNFMA 42
 
 
 hIL12Rb1_VHH19 YDYCGYDVR 43
 
 
 hIL12Rb1_VHH20 YTYSSAFMA 44
 
 
 hIL12Rb1_VHH21 YTYSSAFMA 45
 
 
 hIL12Rb1_VHH22 YTYSSAFMA 46
 
 
 
 
 SEQ
 
 
 
 ID
 
 Name CDR2 NO:
 
 
 hIL12Rb1_VHH1 LITSDRSISYEDSVKA 47
 
 
 hIL12Rb1_VHH2 AIYTRDGGTVYADSVKG 48
 
 
 hIL12Rb1_VHH3 LITSDYSIRYEDSVEG 49
 
 
 hIL12Rb1_VHH4 LITSDRIASYEDSVKG 50
 
 
 hIL12Rb1_VHH5 LITSDRSVSYEDSVKG 51
 
 
 hIL12Rb1_VHH6 AIYTGDGYAYYFYSVKG 52
 
 
 hIL12Rb1_VHH7 GIDSDGSTSYADSVKG 53
 
 
 hIL12Rb1_VHH8 LITSDYSIRYEDSVEG 54
 
 
 hIL12Rb1_VHH9 LITSDYSIRYEDSVEG 55
 
 
 hIL12Rb1_VHH10 GIDSDGSTSYADSVKG 56
 
 
 hIL12Rb1_VHH11 GIDSDGSTSYADSVKG 57
 
 
 hIL12Rb1_VHH12 AIYTRDGGTVYADSVKG 58
 
 
 hIL12Rb1_VHH13 LITSERVISYEDSVKG 59
 
 
 hIL12Rb1_VHH14 GIDSDGSTSYADSVKG 60
 
 
 hIL12Rb1_VHH15 GINSDGSTSYADSVKG 61
 
 
 hIL12Rb1_VHH16 AMYTRDGGTVYADSVKG 62
 
 
 hIL12Rb1_VHH17 LITSDRSVSYEDSVKG 63
 
 
 hIL12Rb1_VHH18 AIYTGDGYAYYFDSVKG 64
 
 
 hIL12Rb1_VHH19 GINSDGSTSYADSVKG 65
 
 
 hIL12Rb1_VHH20 AIYTRDGSPVYADSLKG 66
 
 
 hIL12Rb1_VHH21 AMYTRDGGTVYADSVKG 67
 
 
 hIL12Rb1_VHH22 AIYTRDGGTVYADSVKG 68
 
 
 
 
 SEQ
 
 
 
 ID
 
 Name CDR3 NO:
 
 
 hIL12Rb1_VHH1 SAAARESSWCRSRYRVAS 69
 
 
 hIL12Rb1_VHH2 KIPQPGRASLLDSQTYDY 70
 
 
 hIL12Rb1_VHH3 STAARESSWCRSRYRVAS 71
 
 
 hIL12Rb1_VHH4 SAAARENSWCRSRYRVAS 72
 
 
 hIL12Rb1_VHH5 STAARENNWCRSRYRIAY 73
 
 
 hIL12Rb1_VHH6 MERRIGTRRMTENAEYKY 74
 
 
 hIL12Rb1_VHH7 ESPAGESAWCRNFRGMDY 75
 
 
 hIL12Rb1_VHH8 STAARESSWCRSRYRVAS 76
 
 
 hIL12Rb1_VHH9 STAARESGWCRSRYRVAS 77
 
 
 hIL12Rb1_VHH10 ESPAGESAWCRNERGMDY 78
 
 
 hIL12Rb1_VHH11 ESPAGESAWCRNFRGMDY 79
 
 
 hIL12Rb1_VHH12 KMPQPGRASLLDSQTYDY 80
 
 
 hIL12Rb1_VHH13 SAAARESSWCRSRYRVAS 81
 
 
 hIL12Rb1_VHH14 ESPAGESAWCRNFRGMDY 82
 
 
 hIL12Rb1_VHH15 ESPAGESAWCRNFRGMDY 83
 
 
 hIL12Rb1_VHH16 KIPQPGRASLLDSQTYDY 84
 
 
 hIL12Rb1_VHH17 STAARENNWCRSRYRIAS 85
 
 
 hIL12Rb1_VHH18 MERRSGRRRMTENAEYKY 86
 
 
 hIL12Rb1_VHH19 EGPAGESAWCRNFRGMDY 87
 
 
 hIL12Rb1_VHH20 KIPEPGRISLLDSQTYDY 88
 
 
 hIL12Rb1_VHH21 KIPQPGRASLLDSQTYDY 89
 
 
 hIL12Rb1_VHH22 KIPQPGRASLLDSQTYDY 90
 
and wherein the anti-IL12Rb2 sdAb comprises a CDR1, a CDR2, and a CDR3 in a single row of the following table:
 
 
 
 
 SEQ
 
 
 
 ID
 
 Name CDR1 NO:
 
 
 hIL12Rb2_VHH1 FTVTRYCMG 160
 
 
 hIL12Rb2_VHH2 FTISRYCMG 161
 
 
 hIL12Rb2_VHH3 LTFDDVEMA 162
 
 
 hIL12Rb2_VHH4 FTISRYCMG 163
 
 
 hIL12Rb2_VHH5 FTFSTYAMS 164
 
 
 hIL12Rb2_VHH6 YTYGLFCMG 165
 
 
 hIL12Rb2_VHH7 VTYSRYCMG 166
 
 
 hIL12Rb2_VHH8 FTVSRYCMG 167
 
 
 hIL12Rb2_VHH9 FTISRYCMG 168
 
 
 hIL12Rb2_VHH10 FTVTRYCMG 169
 
 
 hIL12Rb2_VHH11 FTVSRYCMG 170
 
 
 hIL12Rb2_VHH12 VTYSRYCMG 171
 
 
 hIL12Rb2_VHH13 FTISKYCMG 172
 
 
 hIL12Rb2_VHH14 VTYSRYCMG 173
 
 
 hIL12Rb2_VHH15 FTISRYCMG 174
 
 
 hIL12Rb2_VHH16 VTYSRYCMG 175
 
 
 hIL12Rb2_VHH17 LTISRYCMG 176
 
 
 hIL12Rb2_VHH18 FTVDDFAMG 177
 
 
 
 
 SEQ
 
 
 
 ID
 
 Name CDR2 NO:
 
 
 hIL12Rb2_VHH1 IIERDGRTGYADSVKG 178
 
 
 hIL12Rb2_VHH2 IIERDGRTGYADSVKG 179
 
 
 hIL12Rb2_VHH3 SINTDSRVYYVDSVKD 180
 
 
 hIL12Rb2_VHH4 IIERDGRTGYADSVKG 181
 
 
 hIL12Rb2_VHH5 RISSGGGNTYYADAVKG 182
 
 
 hIL12Rb2_VHH6 VVDSPGGRHVADSLKG 183
 
 
 hIL12Rb2_VHH7 TIYSRGIITYYTDSVKG 184
 
 
 hIL12Rb2_VHH8 IIEREGRTGYADSVKG 185
 
 
 hIL12Rb2_VHH9 IIERDGRTGYADSVKG 186
 
 
 hIL12Rb2_VHH10 IIERDGRTGYADSVKG 187
 
 
 hIL12Rb2_VHH11 IIERDGRTGYADSVKG 188
 
 
 hIL12Rb2_VHH12 TIYSRGIITYYTDSVKG 189
 
 
 hIL12Rb2_VHH13 IIERDGRTGYADSVKG 190
 
 
 hIL12Rb2_VHH14 HIYSRGIITYYTDSVKG 191
 
 
 hIL12Rb2_VHH15 IIERDGRTGYADSVKG 192
 
 
 hIL12Rb2_VHH16 HIYSRGIITYYTDSVKG 193
 
 
 hIL12Rb2_VHH17 IIERDGRTGYADSVKG 194
 
 
 hIL12Rb2_VHH18 TISSGGSTYYADSVKG 195
 
 
 
 
 SEQ
 
 
 
 ID
 
 Name CDR3 NO:
 
 
 hIL12Rb2_VHH1 IEGSCRPDFGY 196
 
 
 hIL12Rb2_VHH2 IEGSCRPDFGY 197
 
 
 hIL12Rb2_VHH3 DPWGGDLRGYPNY 198
 
 
 hIL12Rb2_VHH4 IEGSCRPDFGY 199
 
 
 hIL12Rb2_VHH5 DDYYGGSWHPIS 200
 
 
 hIL12Rb2_VHH6 DPEKYCFLESDAGYQY 201
 
 
 hIL12Rb2_VHH7 TRETYGGSGDCDYESVYNY 202
 
 
 hIL12Rb2_VHH8 IEGSCRPDFGY 203
 
 
 hIL12Rb2_VHH9 IEGSCRPDFGY 204
 
 
 hIL12Rb2_VHH10 IEGSCRPDFGY 205
 
 
 hIL12Rb2_VHH11 IEGSCRPDFGY 206
 
 
 hIL12Rb2_VHH12 TRETYGGSGDCDYESVYNY 207
 
 
 hIL12Rb2_VHH13 IEGSCRPDFGY 208
 
 
 hIL12Rb2_VHH14 TRETYGGSGDCGYESVYNY 209
 
 
 hIL12Rb2_VHH15 IEGSCRPDLGY 210
 
 
 hIL12Rb2_VHH16 TRETYGGSGDCSYESVYNH 211
 
 
 hIL12Rb2_VHH17 IEGSCRPDFGY 212
 
 
 hIL12Rb2_VHH18 SSVGCPLGY 213.