Immune checkpoint - CTLA-4 PD-1 2

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CTLA-4 / PD-1 / PD-L1

Immune checkpoint - CTLA-4 PD-1 2

ACRO Biosystems ACRO Biosystems HEK293 Human PD-1 / PDCD1 Protein, Tag Free, Full Length PD-1 PD-1 ECD ACRO Biosystems 7 PD-1 PD-1 PD-1 His PD-1 ECD PD-L1 PD-1 A representative ELISA result showed that immobilized full length human PD1 PD1-HC214, 20 ng/well can bind with human PDL1 with a linear range of 1.2-78ng, which is much higher than the PD1 ECD protein linear range 250ng-1,250ng. Human PD-1/PDCD1 Protein, Tag Free, Full Length Leu 25 - Leu 288 PD1-HC214 20 µg 135,000 PD-1 Cynomolgus Leu 25 - Gln 167 His Tag PD1-C5223 50 µg 113,000 1 mg 800,000 PD-1 Cynomolgus Leu 25 - Gln 167 Fc Tag PD1-C5254 100 µg 75,000 PD-1 Human Leu 25 - Gln 167 His Tag PD1-H5221 100 µg 75,000 1 mg 495,000 PD-1 Human Leu 25 - Gln 167 Fc Tag PD1-H5257 100 µg 75,000 1 mg 500,000 PD-1 Human Leu 25 - Gln 167 Strep Tag PD1-H5284 25 µg 65,000 250 µg 220,000 PD-1 Biotin Human Leu 25 - Gln 167 His Tag & Avi Tag PD1-H82E4 PD-1 Biotin Human Leu 25 - Gln 167 Fc Tag & Avi Tag PD1-H82F1 PD-1 Biotin Human Leu 25 - Gln 167 His Tag & Fc Tag & Avi Tag PD1-H82F2 PD-1 Human Leu 25 - Leu 288 PD1-HC214 20 µg 135,000 PD-1 Mouse Ser 21 - Gln 167 mouse IgG2a Fc Tag PD1-M52A4 3

PD-1 Mouse Leu 25 - Gln 167 His Tag PD1-M5228 100 µg 63,000 PD-1 Mouse Leu 25 - Gln 167 Fc Tag PD1-M5259 100 µg 88,000 1 mg 495,000 PD-1 Biotin Mouse Leu 25 - Gln 167 Fc Tag & Avi Tag PD1-M82F4 PD-1 Rat Leu 25 - Gln 167 Fc Tag PD1-R5253 PD-1 Rat Leu 25 - Gln 167 His Tag PD1-R52H2 100 µg 75,000 PD-1 Rabbit Leu 25 - Gln 167 His Tag PD1-R52H0 100 µg 103,000 1 mg 550,000 PD-1 Rabbit Leu 25 - Gln 167 Fc Tag PD1-RB5251 100 µg 103,000 PD-L1 Cynomolgus Phe 19 - Arg 238 Fc Tag PD1-C5253 100 µg 88,000 1 mg 495,000 PD-L1 Cynomolgus Phe 19 - Arg 238 His Tag PD1-C52H4 100 µg 88,000 1 mg 495,000 PD-L1 Human Phe 19 - Arg 238 His Tag PD1-H5229 100 µg 75,000 1 mg 500,000 PD-L1 Human Phe 19 - Arg 238 Fc Tag PD1-H5258 1 mg 525,000 PD-L1 Human Phe 19 - Arg 238 Strep Tag PD1-H5282 25 µg 65,000 250 µg 220,000 PD-L1 Human Phe 19 - Arg 238 Mouse Fc Tag PD1-H52A3 100 µg 70,000 1 mg 400,000 PD-L1 Biotin Human Phe 19 - Arg 238 His Tag & Avi Tag PD1-H82E5 PD-L1 Biotin Human Phe 19 - Arg 238 Fc Tag & Avi Tag PDL-H82F2 PD-L1 Biotin Human Phe 19 - Arg 238 His Tag & Fc Tag & Avi Tag PD1-H82F3 PD-L1 C13 and N15 Human Phe 19 - Arg 238 His Tag PD1-H9229 5 µg 198,000 20 µg 363,000 PD-L1 Mouse Phe 19 - Thr 238 His Tag PD1-M5220 100 µg 78,000 PD-L1 Mouse Phe 19 - Thr 238 Fc Tag PD1-M5251 200 µg 68,000 1 mg 300,000 PD-L1 Mouse Phe 19 - Thr 238 Mouse Fc Tag PD1-M52A2 100 µg 88,000 1 mg 525,000 PD-L1 Biotin Mouse Phe 19 - Thr 238 Fc Tag & Avi Tag PD1-M82F5 PD-L2 Human Leu 20 - Pro 219 His Tag PD2-H5220 100 µg 65,000 1 mg 400,000 PD-L2 Human Leu 20 - Pro 219 Fc Tag PD2-H5251 100 µg 65,000 1 mg 425,000 PD-L2 Human Leu 20 - Pro 219 Mouse Fc Tag PD2-H52A5 PD-L2 Biotin Human Leu 20 - Pro 219 His Tag & Avi Tag PD2-H82E8 PD-L2 Mouse Leu 20 - Arg 219 Fc Tag PD2-M5254 1mg 450,000 PD-L2 Mouse Leu 20 - Arg 219 mouse IgG2a Fc Tag PD2-M52A5 1mg 450,000 PD-L2 Mouse Leu 20 - Arg 219 His Tag PD2-M52E3 4

PD1 / PD-L1 Inhibitor Screening Kits ELISA ACRO Biosystems PD-1 / PD-L1 ELISA PD1 PDL1 PD-1[Biotin]:PD-L1 Inhibitor Screening Pair EP-101 96 Tests 150,000 PD-1[Biotin]:PD-L1 Inhibitor Screening Pair EP-101 480 Tests 538,000 PD-1 PD-L1 HEK293 PD-1 PD-1 PD-1 PD1-NA001 Immobilized human PD-L1 protein Catalog# A001-214 at 2µg/mL 100 µl/well can bind biotinylated human PD-1 Catalog# A002-214 with a linear range of 0.038-0.6µg/mL when detected by Streptavidin-HRP Catalog# A003-214. Inhibition of PD-1-PD-L1 binding by Anti-PD-1 neutralizing antibody Catalog # PD1-NA001 measured using the PD-1 [Biotinylated] : PD-L1 Inhibitor Screening ELISA Assay Pair Catalog # EP-101. 96Tests 480Tests Human PD-L1 A001-214 25 µg 125 µg Human PD-1-Biotin A002-214 5 µg 25 µg Streptavidin-HRP A003-214 5 µg 25 µg Anti-PD-1 Neutralizing Antibody PD1-NA001 20 µg 100 µg 5

BioXCell In Vivo BioXCell in vivo InVivoMab 0.002 EU/µg 95 CTLA-4 CD152 human BN13 Mouse IgG2a, κ Neu, FC BE0190 CTLA-4 CD152 mouse UC10-4F10-11 Armenian Hamster IgG Neu, WB, FC BE0032 CTLA-4 CD152 mouse 9H10 Syrian Hamster IgG Neu, WB BE0131 CTLA-4 CD152 mouse 9D9 Mouse IgG2b Neu, WB BE0164 PD-1 CD279 human J116 Mouse IgG1, κ BL, Neu BE0188 PD-1 CD279 human J110 Mouse IgG1 FC BE0193 PD-1 CD279 mouse J43 Armenian Hamster IgG BL, Neu, WB BE0033-2 PD-1 CD279 mouse RMP1-14 Rat IgG2a, κ BL, WB BE0146 PD-1 CD279 mouse 29F.1A12 Rat IgG2a, κ BL, Neu, IHC(Fr), IF, WB, FC BE0273 PD-L1 B7-H1 human 29E.2A3 Mouse IgG2b, κ BL, FA, IHC(Fr), FC BE0285 PD-L1 B7-H1 mouse 10F.9G2 Rat IgG2b, κ BL, IHC(Fr), IF, WB, FC BE0101 PD-L2 B7-DC mouse TY25 Rat IgG2a, κ BL, IHC(Fr), FC BE0112 BL Neu FA IHC IF WB FC BE0032 BE0033-2 BE0112 BE0164 BE0188 BE0190 BE0193 BE0273 BE0285 1 mg 42,000 33,000 5 mg 115,000 83,000 25 mg 287,000 187,000 50 mg 438,000 300,000 100 mg 626,000 436,000 BE0101 BE0131 BE0146 1 mg 42,000 33,000 5 mg 122,000 83,000 25 mg 339,000 205,000 50 mg 501,000 327,000 100 mg 741,000 463,000 6

BioXCell InVivoPlus Bio X Cell InVivoMab InVivoPlus 0.001 EU/µg 95 5 FACS ELISA CTLA-4 CD152 mouse UC10-4F10-11 Armenian Hamster IgG Neu, WB, FC BP0032 CTLA-4 CD152 mouse 9D9 Mouse IgG2b Neu, WB BP0164 CTLA-4 CD152 mouse 9H10 Syrian Hamster IgG Neu, WB BP0131 PD-1 CD279 mouse J43 Armenian Hamster IgG BL, Neu, WB BP0033-2 PD-1 CD279 mouse RMP1-14 Rat IgG2a, κ BL, WB BP0146 PD-1 CD279 mouse 29F.1A12 Rat IgG2a, κ BL, Neu, IHC(Fr), IF, WB, FC BP0273 PD-L1 B7-H1 mouse 10F.9G2 Rat IgG2b, κ BL, IHC(Fr), IF, WB, FC BP0101 BL Neu FA IHC IF WB FC BP0032 BP0033-2 BP0164 BP0273 5 mg 143,000 102,000 25 mg 365,000 236,000 50 mg 561,000 381,000 100 mg 800,000 555,000 BP0101 BP0131 BP0146 5 mg 153,000 102,000 25 mg 433,000 259,000 50 mg 642,000 417,000 100 mg 951,000 590,000 in vivo BioXCell PBS 1X InVivoPlus InVivoMab InVivoPure Dilution Buffers 0.0005 EU/ug InVivoPure ph 6.5 Dilution Buffer IP0065 50 ml 18,000 12,000 InVivoPure ph 7.0 Dilution Buffer IP0070 50 ml 18,000 12,000 InVivoPure ph 8.0 Dilution Buffer IP0080 50 ml 18,000 12,000 InVivoPure ph 6.0T Dilution Buffer 0.01% TWEEN 80 IPT060 50 ml 18,000 12,000 InVivoPure ph 6.5T Dilution Buffer 0.01% TWEEN 80 IPT065 50 ml 18,000 12,000 InVivoPure ph 8.0T Dilution Buffer 0.01% TWEEN 80 IPT080 50 ml 18,000 12,000 6 BioXCell TEL 03-3864-1469 7

BioXCell IgG Human IgG IgG Fc in vivo ELISA, WB, IF, IHC, IP, FCM InVivoPure ph 7.0 Dilution Buffer P7 InVivoPlus Human IgG1 Isotype control 5 mg, 25 mg, 50 mg, 100 mg BP0297 InVivoPlus Human IgG2 Isotype control 5 mg, 25 mg, 50 mg, 100 mg BP0301 InVivoMab Human IgG1 Isotype control 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0297 InVivoMab Human IgG2 Isotype control 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0301 InVivoPlus Mouse IgG1 Isotype control; Unknown Specificity MOPC-21 5 mg, 25 mg, 50 mg, 100 mg BP0083 InVivoPlus Mouse IgG2a Isotype control; Unknown Specificity C1.18.4 5 mg, 25 mg, 50 mg, 100 mg BP0085 InVivoPlus Mouse IgG2b Isotype control; Unknown Specificity MPC-11 5 mg, 25 mg, 50 mg, 100 mg BP0086 InVivoPlus Rat IgG1 Isotype control; anti Horseradish Peroxidase HRPN 5 mg, 25 mg, 50 mg, 100 mg BP0088 InVivoPlus Rat IgG1 Isotype control; anti Trinitrophenol TNP6A7 5 mg, 25 mg, 50 mg, 100 mg BP0290 InVivoPlus Rat IgG2a Isotype control; anti Trinitrophenol 2A3 5 mg, 25 mg, 50 mg, 100 mg BP0089 InVivoPlus Rat IgG2b Isotype control; anti KLH LTF-2 5 mg, 25 mg, 50 mg, 100 mg BP0090 InVivoPlus Polyclonal Armenian Hamster IgG Polyclonal 5 mg, 25 mg, 50 mg, 100 mg BP0091 InVivoPlus Polyclonal Syrian Hamster IgG Polyclonal 5 mg, 25 mg, 50 mg, 100 mg BP0087 InVivoMab Armenian Hamster IgG Isotype control; anti GST PIP 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0260 InVivoMab Mouse IgG1 Isotype control; Unknown Specificity MOPC-21 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0083 InVivoMab Mouse IgG2a Isotype control; Unknown Specificity C1.18.4 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0085 InVivoMab Mouse IgG2b Isotype control; Unknown Specificity MPC-11 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0086 InVivoMab Rat IgG1 Isotype control; anti Horseradish Peroxidase HRPN 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0088 InVivoMab Rat IgG1 Isotype control; anti Trinitrophenol TNP6A7 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0290 InVivoMab Rat IgG2a Isotype control; anti Trinitrophenol 2A3 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0089 InVivoMab Rat IgG2b Isotype control; anti KLH LTF-2 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0090 InVivoMab Polyclonal Armenian Hamster IgG Polyclonal 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0091 InVivoMab Polyclonal Hamster IgG f(ab')2 Fragments Polyclonal 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0091-FAB InVivoMab Polyclonal Goat IgG Polyclonal 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0130 InVivoMab Polyclonal Human IgG Polyclonal 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0092 InVivoMab Polyclonal Mouse IgG Polyclonal 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0093 InVivoMab Polyclonal Rabbit IgG Polyclonal 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0095 InVivoMab Polyclonal Rat IgG Polyclonal 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0094 InVivoMab Polyclonal Syrian Hamster IgG Polyclonal 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0087 InVivoMab Recombinant Human IgG1 Fc Human Fc-G1 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0096 InVivoMab Recombinant Mouse IgG2a Fc Mouse Fc-G2a 1 mg, 5 mg, 25 mg, 50 mg, 100 mg BE0097 InVivoPlus Isotype Control 5 mg 143,000 102,000 25 mg 365,000 236,000 50 mg 561,000 381,000 100 mg 800,000 555,000 BE0091-FAB 5 mg 188,000 110,000 25 mg 318,000 177,000 50 mg 522,000 333,000 100 mg 730,000 544,000 InVivoMab Isotype Control 1 mg 42,000 33,000 5 mg 115,000 83,000 25 mg 287,000 187,000 50 mg 438,000 300,000 100 mg 626,000 436,000 8

Matriks Biotechnology ADA ELISA Matriks Biotechnology Anti- Drug Antibody, ADA ELISA ADA CTLA-4, PD-1, PD-L1 ADA ELISA Cmax-Cmin 10ul~ ready-to-use 96 70 140 ADA ELISA ELISA Avelumab Bavencio SHIKARI Q-AVE TR-Q-AVEV1 1 Kit 193,000 Nivolumab Opdivo SHIKARI Q-NIVO TR-Q-NIVOV1 1 Kit 193,000 Pembrolizumab Keytruda SHIKARI Q-PEM TR-PEMV1 1 Kit 207,000 Ipilimumab Yervoy SHIKARI Q-IPI TR-IPIV1 1 Kit 207,000 ADA ELISA Antibodies to Avelumab Bavencio SHIKARI S-ATAV TR-A-AVEV1 1 Kit 193,000 Antibodies to Nivolumab Opdivo SHIKARI S-ATN TR-ATNV1 1 Kit 193,000 Antibodies to Pembrolizumab Keytruda SHIKARI S-ATP TR-A-PEMV1 1 Kit 193,000 Antibodies to Ipilimumab Yervoy SHIKARI S-ATI TR-AIPIV1 1 Kit 193,000 9

Sino Biological Sino Biological FCM assay for PD-L1 antibody IHC assay for PD-L1 antibody WB assay for CTLA-4 antibody Flow Cytometry analysis of PD-L1 antibody 50010-R401 reacting on mouse splenocytes. Immunohistochemical analysis of paraffin-embedded human placenta using PD-L1 antibody 10084-R015 at 5µg/mL. Western Blot analysis of CTLA4 antibody (11159-RP02, 1:500 dilution) measured using Jurkat Membrane Lysate (20µg/lane). Human CTLA-4 / CD152 Antibody, Rabbit PAb WB, ELISA 11159-RP02 100 µg 38,000 Human PD1 / PDCD1 Antibody, Rabbit MAb ELISA 10377-R002 100 µg 58,000 Mouse PD1 / PDCD1 / CD279 Antibody, Rabbit PAb ELISA, IHC-P 50124-RP02 100 µg 58,000 Human PD-L1 / B7-H1 / CD274 Antibody, Rabbit MAb ELISA, IHC-P 10084-R015 100 µg 58,000 Mouse PD-L1 / B7-H1 / CD274 Antibody, Rabbit MAb FCM 50010-R401 100 µg 58,000 Human B7-H5 / GI24 / VISTA Antibody, Rabbit PAb ELISA 13482-T16 100 µg 58,000 Human CD40 / TNFRSF5 Antibody, Mouse MAb ICC/IF, IF, FCM 10774-MM03 100 µg 58,000 Human CD80 / B7-1 Antibody, Rabbit PAb WB, ELISA, IHC-P 10698-T56 100 µg 38,000 Human CD155 / PVR / NECL5 Antibody, Rabbit MAb WB, ELISA, IP 10109-R114 100 µg 58,000 Mouse CD155 / PVR Antibody, Rabbit MAb ICC/IF, IF, FCM 50259-R305 100 µg 58,000 Human CEACAM1 / CD66a Antibody PE, Rabbit MAb FCM 10822-R103-P 100 Tests 48,000 Mouse CEACAM1 / CD66a Antibody, Rabbit MAb IHC-P 50571-R030 100 µg 50,000 Mouse TIGIT / VSTM3 Antibody, Rabbit PAb ELISA, IHC-P 50939-T24 100 µg 38,000 Human TIM-3 / HAVCR2 Antibody, Rabbit MAb ELISA 10390-R024 100 µg 58,000 10

Sino Biological Sino Biological cdna High purity < 1 EU/µg His Fc Validated activity 3.0 Human ICOS Ligand Protein (His Tag) 2.5 Abs.(OD450nm-Blank) 2.0 1.5 1.0 0.5 0.0 1E-4 1E-3 0.01 0.1 1 10 Human ICOS Protein (His & Fc Tag) Con.(ug/ml) The purity of PD-L1 10084-H02H was >95% as determined by SDS-PAGE. The activity assay of ICOS Ligand protein Cat: 11559-H08H by binding to ICOS Protein Cat: 10344-H03H. EC50= 0.30µg/ml Human CTLA4 / CD152 Protein His Tag 11159-H08H 100 µg 32,000 Human PD1 / PDCD1 Protein His Tag 10377-H08H 100 µg 45,000 Human PD-L1 / B7-H1 / CD274 Protein Fc Tag 10084-H02H 100 µg 45,000 Human PD-L1 / B7-H1 / CD274 Protein His Tag 10084-H08H 100 µg 45,000 Human 4-1BBL / CD137L Protein Fc Tag, ECD 15693-H01H 20 µg 35,000 Human B7-H5 / Gi24 / VISTA Protein His Tag 13482-H08H 50 µg 45,000 Mouse B7-H5 / GI24 / VISTA Protein ECD, His Tag 51550-M08H 50 µg 45,000 Human BTLA Protein Fc Tag 11895-H02H 50 µg 45,000 Human CD80 / B7-1 Protein His Tag 10698-H08H 100 µg 50,000 Human CD86 / B7-2 Protein His Tag 10699-H08H 100 µg 50,000 Human CD137 / 4-1BB / TNFRSF9 Protein His Tag 10041-H08H 100 µg 45,000 Human CD155 / PVR / NECL5 Protein Fc Tag 10109-H02H 50 µg 45,000 Human GITR / TNFRSF18 Protein His Tag, ECD 13643-H08H 100 µg 45,000 Human ICOS / AILIM / CD278 Protein His & Fc Tag 10344-H03H 50 µg 45,000 Human LAG3 / CD223 / Lymphocyte activation gene 3 Protein Fc Tag 16498-H02H 50 µg 45,000 Human TIGIT / VSTM3 Protein His Tag 10917-H08H 10 µg 45,000 Human TIM-3 / HAVCR2 Protein His Tag 10390-H08H 50 µg 50,000 Human TNFRSF4 / OX40 / CD134 Protein His Tag 10481-H08H 50 µg 45,000 11

Cloud-Clone ELISA Cloud-Clone ELISA 10 4,000 8,000 ELISA CTLA-4 / PD-1 / PD-L1 / PD-L2 ELISA Human Cytotoxic T-Lymphocyte Associated Antigen 4 / CTLA4 ELISA Kit Human PD-1 / Programmed Cell Death Protein 1 / PDCD1 ELISA Kit Human PD-L1 / Programmed Cell Death Protein 1 Ligand 1 / PDCD1LG1 ELISA Kit Human PD-L2 / Programmed Cell Death Protein 1 Ligand 2 / PDCD1LG2 ELISA Kit 31.2-2,000 pg/ml 12.4 pg/ml SEB230HU 96 Test 127,800 0.156-10 ng/ml 0.063 ng/ml SEA751HU 96 Test 120,600 0.156-10 ng/ml 0.056 ng/ml SEA788HU 96 Test 120,600 0.156-10 ng/ml 0.062 ng/ml SEA789HU 96 Test 120,600 SEA788HU PMID: #24653632 Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications Chin J Cancer Res. 2014 Feb; 26 1 : 104-111. PMID: #24732592 High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-Cell lymphoma: results from a French multicenter clinical trial. Leukemia. 2014 Dec;28 12 :2367-75. PMID: #24816853 PD-L1 gene polymorphisms and low serum level of PD-L1 protein are associated to type 1 diabetes in Chile. Diabetes Metab Res Rev. 2014 Nov;30 8 :761-6. PMID: #26686046 Ratios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B-cell lymphoma: a population-based study. Lancet Haematol. 2015 Oct;2 10 :e445-55. PMID: #27039170 High levels of the soluble programmed death-ligand spd-l1 identify hepatocellular carcinoma patients with a poor prognosis. Eur J Cancer. 2016 May;59:152-9. SEA789HU PMID: #27256004 Serum levels of soluble programmed cell death ligand 1 as a prognostic factor on the first-line treatment of metastatic or recurrent gastric cancer. J Cancer Res Clin Oncol. 2016 Aug;142 8 :1727-38. IWAI CHEMICALS COMPANY 101-0032 1-5-11 TEL 03-3864-1459 FAX 03-3864-1494 TEL 03-3864-1457 FAX 03-3864-1492 TEL 03-3864-1412 FAX 03-3864-1433 TEL 029-847-0321 TEL 055-976-3081 TEL 042-548-6480 TEL 045-974-4581 TEL 04-7140-8371 http://www.iwai-chem.co.jp/ TEL 03-3864-1469 FAX 03-3864-1497 2018 4 1