Immune checkpoint - CTLA-4 PD-1 2

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1 CTLA-4 / PD-1 / PD-L1

2 Immune checkpoint - CTLA-4 PD-1 2

3 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 ng, 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-HC µg 135,000 PD-1 Cynomolgus Leu 25 - Gln 167 His Tag PD1-C µg 113,000 1 mg 800,000 PD-1 Cynomolgus Leu 25 - Gln 167 Fc Tag PD1-C µg 75,000 PD-1 Human Leu 25 - Gln 167 His Tag PD1-H µg 75,000 1 mg 495,000 PD-1 Human Leu 25 - Gln 167 Fc Tag PD1-H µg 75,000 1 mg 500,000 PD-1 Human Leu 25 - Gln 167 Strep Tag PD1-H µg 65, 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-HC µg 135,000 PD-1 Mouse Ser 21 - Gln 167 mouse IgG2a Fc Tag PD1-M52A4 3

4 PD-1 Mouse Leu 25 - Gln 167 His Tag PD1-M µg 63,000 PD-1 Mouse Leu 25 - Gln 167 Fc Tag PD1-M 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-RB µg 103,000 PD-L1 Cynomolgus Phe 19 - Arg 238 Fc Tag PD1-C 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-H µg 75,000 1 mg 500,000 PD-L1 Human Phe 19 - Arg 238 Fc Tag PD1-H mg 525,000 PD-L1 Human Phe 19 - Arg 238 Strep Tag PD1-H µg 65, 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-H µg 198, µg 363,000 PD-L1 Mouse Phe 19 - Thr 238 His Tag PD1-M µg 78,000 PD-L1 Mouse Phe 19 - Thr 238 Fc Tag PD1-M 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-H µg 65,000 1 mg 400,000 PD-L2 Human Leu 20 - Pro 219 Fc Tag PD2-H 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

5 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 Tests 150,000 PD-1[Biotin]:PD-L1 Inhibitor Screening Pair EP Tests 538,000 PD-1 PD-L1 HEK293 PD-1 PD-1 PD-1 PD1-NA001 Immobilized human PD-L1 protein Catalog# A at 2µg/mL 100 µl/well can bind biotinylated human PD-1 Catalog# A with a linear range of µg/mL when detected by Streptavidin-HRP Catalog# A 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 Tests 480Tests Human PD-L1 A µg 125 µg Human PD-1-Biotin A µg 25 µg Streptavidin-HRP A µg 25 µg Anti-PD-1 Neutralizing Antibody PD1-NA µg 100 µg 5

6 BioXCell In Vivo BioXCell in vivo InVivoMab 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 BE 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 BE BE0112 BE0164 BE0188 BE0190 BE0193 BE0273 BE mg 42,000 33,000 5 mg 115,000 83, mg 287, , mg 438, , mg 626, ,000 BE0101 BE0131 BE mg 42,000 33,000 5 mg 122,000 83, mg 339, , mg 501, , mg 741, ,000 6

7 BioXCell InVivoPlus Bio X Cell InVivoMab InVivoPlus 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 BP 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 BP BP0164 BP mg 143, , mg 365, , mg 561, , mg 800, ,000 BP0101 BP0131 BP mg 153, , mg 433, , mg 642, , mg 951, ,000 in vivo BioXCell PBS 1X InVivoPlus InVivoMab InVivoPure Dilution Buffers EU/ug InVivoPure ph 6.5 Dilution Buffer IP ml 18,000 12,000 InVivoPure ph 7.0 Dilution Buffer IP ml 18,000 12,000 InVivoPure ph 8.0 Dilution Buffer IP ml 18,000 12,000 InVivoPure ph 6.0T Dilution Buffer 0.01% TWEEN 80 IPT ml 18,000 12,000 InVivoPure ph 6.5T Dilution Buffer 0.01% TWEEN 80 IPT ml 18,000 12,000 InVivoPure ph 8.0T Dilution Buffer 0.01% TWEEN 80 IPT ml 18,000 12,000 6 BioXCell TEL

8 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 C 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 C 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, , mg 365, , mg 561, , mg 800, ,000 BE0091-FAB 5 mg 188, , mg 318, , mg 522, , mg 730, ,000 InVivoMab Isotype Control 1 mg 42,000 33,000 5 mg 115,000 83, mg 287, , mg 438, , mg 626, ,000 8

9 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 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

10 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 R401 reacting on mouse splenocytes. Immunohistochemical analysis of paraffin-embedded human placenta using PD-L1 antibody 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 RP µg 38,000 Human PD1 / PDCD1 Antibody, Rabbit MAb ELISA R µg 58,000 Mouse PD1 / PDCD1 / CD279 Antibody, Rabbit PAb ELISA, IHC-P RP µg 58,000 Human PD-L1 / B7-H1 / CD274 Antibody, Rabbit MAb ELISA, IHC-P R µg 58,000 Mouse PD-L1 / B7-H1 / CD274 Antibody, Rabbit MAb FCM R µg 58,000 Human B7-H5 / GI24 / VISTA Antibody, Rabbit PAb ELISA T µg 58,000 Human CD40 / TNFRSF5 Antibody, Mouse MAb ICC/IF, IF, FCM MM µg 58,000 Human CD80 / B7-1 Antibody, Rabbit PAb WB, ELISA, IHC-P T µg 38,000 Human CD155 / PVR / NECL5 Antibody, Rabbit MAb WB, ELISA, IP R µg 58,000 Mouse CD155 / PVR Antibody, Rabbit MAb ICC/IF, IF, FCM R µg 58,000 Human CEACAM1 / CD66a Antibody PE, Rabbit MAb FCM R103-P 100 Tests 48,000 Mouse CEACAM1 / CD66a Antibody, Rabbit MAb IHC-P R µg 50,000 Mouse TIGIT / VSTM3 Antibody, Rabbit PAb ELISA, IHC-P T µg 38,000 Human TIM-3 / HAVCR2 Antibody, Rabbit MAb ELISA R µg 58,000 10

11 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) E-4 1E Human ICOS Protein (His & Fc Tag) Con.(ug/ml) The purity of PD-L H02H was >95% as determined by SDS-PAGE. The activity assay of ICOS Ligand protein Cat: H08H by binding to ICOS Protein Cat: H03H. EC50= 0.30µg/ml Human CTLA4 / CD152 Protein His Tag H08H 100 µg 32,000 Human PD1 / PDCD1 Protein His Tag H08H 100 µg 45,000 Human PD-L1 / B7-H1 / CD274 Protein Fc Tag H02H 100 µg 45,000 Human PD-L1 / B7-H1 / CD274 Protein His Tag H08H 100 µg 45,000 Human 4-1BBL / CD137L Protein Fc Tag, ECD H01H 20 µg 35,000 Human B7-H5 / Gi24 / VISTA Protein His Tag H08H 50 µg 45,000 Mouse B7-H5 / GI24 / VISTA Protein ECD, His Tag M08H 50 µg 45,000 Human BTLA Protein Fc Tag H02H 50 µg 45,000 Human CD80 / B7-1 Protein His Tag H08H 100 µg 50,000 Human CD86 / B7-2 Protein His Tag H08H 100 µg 50,000 Human CD137 / 4-1BB / TNFRSF9 Protein His Tag H08H 100 µg 45,000 Human CD155 / PVR / NECL5 Protein Fc Tag H02H 50 µg 45,000 Human GITR / TNFRSF18 Protein His Tag, ECD H08H 100 µg 45,000 Human ICOS / AILIM / CD278 Protein His & Fc Tag H03H 50 µg 45,000 Human LAG3 / CD223 / Lymphocyte activation gene 3 Protein Fc Tag H02H 50 µg 45,000 Human TIGIT / VSTM3 Protein His Tag H08H 10 µg 45,000 Human TIM-3 / HAVCR2 Protein His Tag H08H 50 µg 50,000 Human TNFRSF4 / OX40 / CD134 Protein His Tag H08H 50 µg 45,000 11

12 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 ,000 pg/ml 12.4 pg/ml SEB230HU 96 Test 127, ng/ml ng/ml SEA751HU 96 Test 120, ng/ml ng/ml SEA788HU 96 Test 120, ng/ml ng/ml SEA789HU 96 Test 120,600 SEA788HU PMID: # Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications Chin J Cancer Res Feb; 26 1 : PMID: # 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 Dec;28 12 : PMID: # PD-L1 gene polymorphisms and low serum level of PD-L1 protein are associated to type 1 diabetes in Chile. Diabetes Metab Res Rev Nov;30 8 : PMID: # Ratios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B-cell lymphoma: a population-based study. Lancet Haematol Oct;2 10 :e PMID: # High levels of the soluble programmed death-ligand spd-l1 identify hepatocellular carcinoma patients with a poor prognosis. Eur J Cancer May;59: SEA789HU PMID: # 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 Aug;142 8 : IWAI CHEMICALS COMPANY TEL FAX TEL FAX TEL FAX TEL TEL TEL TEL TEL TEL FAX

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