JP2020517658A5 - - Google Patents
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- JP2020517658A5 JP2020517658A5 JP2019557434A JP2019557434A JP2020517658A5 JP 2020517658 A5 JP2020517658 A5 JP 2020517658A5 JP 2019557434 A JP2019557434 A JP 2019557434A JP 2019557434 A JP2019557434 A JP 2019557434A JP 2020517658 A5 JP2020517658 A5 JP 2020517658A5
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- peptide
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- 108090000765 processed proteins & peptides Proteins 0.000 claims description 96
- 206010028980 Neoplasm Diseases 0.000 claims description 56
- 239000000203 mixture Substances 0.000 claims description 44
- 201000011510 cancer Diseases 0.000 claims description 40
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 21
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 21
- 210000002744 extracellular matrix Anatomy 0.000 claims description 21
- 230000001024 immunotherapeutic effect Effects 0.000 claims description 16
- 108010047303 von Willebrand Factor Proteins 0.000 claims description 16
- 102100036537 von Willebrand factor Human genes 0.000 claims description 16
- 229960001134 von willebrand factor Drugs 0.000 claims description 16
- 108091008036 Immune checkpoint proteins Proteins 0.000 claims description 13
- 102000037982 Immune checkpoint proteins Human genes 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 238000002560 therapeutic procedure Methods 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 9
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 8
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- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 6
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- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 6
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 6
- 239000002955 immunomodulating agent Substances 0.000 claims description 6
- ZADWXFSZEAPBJS-SNVBAGLBSA-N (2r)-2-amino-3-(1-methylindol-3-yl)propanoic acid Chemical compound C1=CC=C2N(C)C=C(C[C@@H](N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-SNVBAGLBSA-N 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 102000004237 Decorin Human genes 0.000 claims description 4
- 108090000738 Decorin Proteins 0.000 claims description 4
- 239000000556 agonist Substances 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 claims description 3
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- 239000003112 inhibitor Substances 0.000 claims description 3
- 230000002601 intratumoral effect Effects 0.000 claims description 3
- WKHJQIQDQXGUOD-UHFFFAOYSA-N 4-(benzylamino)-3-hydroxy-2,2-dimethyl-3,4-dihydrobenzo[g]chromene-5,10-dione Chemical compound OC1C(C)(C)OC(C(C2=CC=CC=C2C2=O)=O)=C2C1NCC1=CC=CC=C1 WKHJQIQDQXGUOD-UHFFFAOYSA-N 0.000 claims description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 2
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 229940123189 CD40 agonist Drugs 0.000 claims description 2
- 101150013553 CD40 gene Proteins 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 102000004127 Cytokines Human genes 0.000 claims description 2
- 108090000695 Cytokines Proteins 0.000 claims description 2
- 102100029722 Ectonucleoside triphosphate diphosphohydrolase 1 Human genes 0.000 claims description 2
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 2
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 claims description 2
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 claims description 2
- 101001012447 Homo sapiens Ectonucleoside triphosphate diphosphohydrolase 1 Proteins 0.000 claims description 2
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 claims description 2
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims description 2
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 claims description 2
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- 102000002698 KIR Receptors Human genes 0.000 claims description 2
- 102000017578 LAG3 Human genes 0.000 claims description 2
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- FBKMWOJEPMPVTQ-UHFFFAOYSA-N N'-(3-bromo-4-fluorophenyl)-N-hydroxy-4-[2-(sulfamoylamino)ethylamino]-1,2,5-oxadiazole-3-carboximidamide Chemical compound NS(=O)(=O)NCCNC1=NON=C1C(=NO)NC1=CC=C(F)C(Br)=C1 FBKMWOJEPMPVTQ-UHFFFAOYSA-N 0.000 claims description 2
- YGACXVRLDHEXKY-WXRXAMBDSA-N O[C@H](C[C@H]1c2c(cccc2F)-c2cncn12)[C@H]1CC[C@H](O)CC1 Chemical compound O[C@H](C[C@H]1c2c(cccc2F)-c2cncn12)[C@H]1CC[C@H](O)CC1 YGACXVRLDHEXKY-WXRXAMBDSA-N 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 claims description 2
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 claims description 2
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 2
- 206010057644 Testis cancer Diseases 0.000 claims description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 claims description 2
- VYWQTJWGWLKBQA-UHFFFAOYSA-N [amino(hydroxy)methylidene]azanium;chloride Chemical compound Cl.NC(N)=O VYWQTJWGWLKBQA-UHFFFAOYSA-N 0.000 claims description 2
- 239000012190 activator Substances 0.000 claims description 2
- 229960003852 atezolizumab Drugs 0.000 claims description 2
- 229950002916 avelumab Drugs 0.000 claims description 2
- 230000001588 bifunctional effect Effects 0.000 claims description 2
- 239000008280 blood Substances 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 claims description 2
- 238000002659 cell therapy Methods 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 238000002512 chemotherapy Methods 0.000 claims description 2
- 208000012191 childhood neoplasm Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 229950009791 durvalumab Drugs 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 210000002308 embryonic cell Anatomy 0.000 claims description 2
- IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 210000004392 genitalia Anatomy 0.000 claims description 2
- 208000005017 glioblastoma Diseases 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 230000001571 immunoadjuvant effect Effects 0.000 claims description 2
- 239000000568 immunological adjuvant Substances 0.000 claims description 2
- 229950009034 indoximod Drugs 0.000 claims description 2
- 238000001361 intraarterial administration Methods 0.000 claims description 2
- 229960005386 ipilimumab Drugs 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- -1 norhalman Chemical compound 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 230000005855 radiation Effects 0.000 claims description 2
- 206010038038 rectal cancer Diseases 0.000 claims description 2
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- 229950007217 tremelimumab Drugs 0.000 claims description 2
- 238000002255 vaccination Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 14
- 229940079593 drug Drugs 0.000 claims 4
- 238000011275 oncology therapy Methods 0.000 claims 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 102100034256 Mucin-1 Human genes 0.000 claims 1
- 108010008707 Mucin-1 Proteins 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 241000283080 Proboscidea <mammal> Species 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
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- 238000000034 method Methods 0.000 description 29
- 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 description 1
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- 229960003301 nivolumab Drugs 0.000 description 1
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- 239000000546 pharmaceutical excipient Substances 0.000 description 1
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Description
ๆฌ็บๆใฎไปปๆใฎๆนๆณใพใใฏใทในใใ ใฏใๆฌ่จ่ผใฎไปปๆใฎ่ฆ็ด ใใใณ/ใพใใฏ็นๅพดใใใณ/ใพใใฏๆฎต้ใๅซใ๏ผcomprise/include/contain๏ผ/ๆใใใฎใงใฏใชใใใใใใใใชใใใพใใฏใใใใใๆฌ่ณช็ใซใชใใใฎใงใใฃใฆใใใใใใใใฃใฆใไปปๆใฎ่ซๆฑ้
ใซใใใฆใ็จ่ชใใใใใชใ๏ผconsisting of๏ผใใพใใฏใใใใๆฌ่ณช็ใซใชใ๏ผconsisting essentially of๏ผใใฏใๆไธใฎ่ซๆฑ้
ใฎ็ฏๅฒใใ้ๅธธใชใ้้ๅฎใฎ้ฃ็ตๅ่ฉใไฝฟ็จใใใใงใใใ็ฏๅฒใใๅคใใใใใซใไธ่จใฎ้้ๅฎใฎ้ฃ็ตๅ่ฉใฎใใใใใง็ฝฎใๆใใใๅพใใใๆฌ่ณช็ใซใ่จ่ผใฎ่ฆ็ด ใใใใชใใ็ตๆ็ฉใฏใไปปๆใฎใใใชใๆดปๆงๆๅใๆ้คใใใใ่ฌๅญฆ็่ณฆๅฝขๅคใใใใใกใผใๆง้ ๆๅใชใฉใฏๆ้คใใชใใ
[ๆฌ็บๆ1001]
็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใๅ ็ซ็ๆณ็จๆไฝใๅซใ็ตๆ็ฉใ
[ๆฌ็บๆ1002]
ๅ่จECM่ฆชๅๆงใใใใใ่็คๅขๆฎๅ ๅญ-2๏ผPlGF-2๏ผใซ็ฑๆฅใใใใใใใๅซใใๆฌ็บๆ1001ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1003]
ๅ่จใใใใใSEQ ID NO:1ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใๆฌ็บๆ1002ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1004]
ๅ่จใใใใใSEQ ID NO:1ใๅซใใๆฌ็บๆ1002ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1005]
ๅ่จใใใใใใใฉใณใปใดใฃใฌใใฉใณใๅ ๅญ๏ผVWF๏ผใใใใใๅซใใๆฌ็บๆ1001ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1006]
ๅ่จVWFใใใใใVWF A1ใพใใฏA3ใใใใใงใใใๆฌ็บๆ1005ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1007]
ๅ่จVWFใใใใใSEQ ID NO:3ใSEQ ID NO:11ใพใใฏใใใใฎๆญ็ใจๅฐใชใใจใ85๏ผ ๅไธใฎใใใใใๅซใใๆฌ็บๆ1006ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1008]
ๅ่จVWFใใใใใSEQ ID NO:3ใพใใฏSEQ ID NO:11ใๅซใใๆฌ็บๆ1007ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1009]
ๅ่จใใใใใCXCL-12ใใใใใๅซใใๆฌ็บๆ1001ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1010]
ๅ่จCXCL-12ใใใใใCXCL-12ฮณใใใใใๅซใใๆฌ็บๆ1009ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1011]
ๅ่จใใใใใSEQ ID NO:2ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใๆฌ็บๆ1010ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1012]
ๅ่จใใใใใๅ่จๆไฝใจๅ ฑๆ็ตๅใใฆใใใๆฌ็บๆ1001ใ1011ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1013]
ๅ่จใใใใใไบๅฎ่ฝๆงใชใณใซใผใซใใฃใฆๅ่จๆไฝใซๆถๆฉใใใฆใใใๆฌ็บๆ1001ใ1012ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1014]
ๅ่จๅ ็ซ็ๆณ็จๆไฝใๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใๅซใใๆฌ็บๆ1001ใ1013ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1015]
ๅ่จๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใCTLA4ๆไฝใPD-L1ๆไฝใพใใฏPD-1ๆไฝใๅซใใๆฌ็บๆ1014ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1016]
ๅ่จๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใใใณใใญใชใบใใใใใใซใใใใขใใพใชใบใใใใคใใชใ ใใใใใฌใกใชใ ใใใใขใใซใใใพใใฏใใฅใซใใซใใใๅซใใๆฌ็บๆ1014ใพใใฏ1015ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1017]
ๅ่จๅ ็ซ็ๆณ็จๆไฝใCD-40ใขใดใในใๆไฝใๅซใใๆฌ็บๆ1001ใ1013ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1018]
ๅ่จๆไฝใใใๅๆไฝใงใใใๆฌ็บๆ1001ใ1017ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1019]
ใใใใๅฏพๆไฝใฎๆฏใ็ด1:1ใ10:1ใงใใใๆฌ็บๆ1001ใ1018ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1020]
็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ2ใฎๅ ็ซ็ๆณ็จๆไฝใใใใซๅซใใๆฌ็บๆ1001ใ1019ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1021]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-L1ๆไฝใๅซใใๆฌ็บๆ1020ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1022]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-1ๆไฝใๅซใใๆฌ็บๆ1020ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1023]
ๆฌ็บๆ1001ใ1022ใฎใใใใใฎ็ตๆ็ฉใๅฏพ่ฑกใซๆไธใใๆฎต้ใๅซใใๅฏพ่ฑกใซใใใใใใๅฆ็ฝฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1024]
ๅ่จ็ตๆ็ฉใๅ จ่บซๆไธใใใใใใพใใฏ่ ซ็ๅ ๆณจๅฐใ่ ซ็ๅจๅฒๆณจๅฐใๅ่ๅ ๆณจๅฐใใใใฏ็ตใซใใผใใซๆณจๅฐใซใใฃใฆๆไธใใใใๆฌ็บๆ1023ใฎๆนๆณใ
[ๆฌ็บๆ1025]
ๅ่จใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใๅ่จๆไฝใฎๆไธ้ใใ่ฉฒใใใใใชใใงๆไธใใใ่ฉฒๆไฝใฎๆๅฐๆๅน้ใใๅฐใชใใๆฌ็บๆ1023ใพใใฏ1024ใฎๆนๆณใ
[ๆฌ็บๆ1026]
ๅ่จใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใๅ่จๆไฝใฎๆไธ้ใใ่ฉฒใใใใใชใใงๆไธใใใ่ฉฒๆไฝใฎๆๅฐๆๅน้ใใๅฐใชใใจใ10๏ผ ๅฐใชใใๆฌ็บๆ1025ใฎๆนๆณใ
[ๆฌ็บๆ1027]
ๆฃ่ ใใใใๅ ็ซ็ๆณ่ฌใงไปฅๅใซๅฆ็ฝฎใใใใใจใใใใๆฌ็บๆ1023ใ1026ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1028]
ไปฅๅใฎใใๅ ็ซ็ๆณ่ฌใใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใๅซใใใฎใงใใฃใใๆฌ็บๆ1027ใฎๆนๆณใ
[ๆฌ็บๆ1029]
ๅ่จๅฏพ่ฑกใใไปฅๅใฎใใๅ ็ซ็ๆณ่ฌใซใใใฐใฌใผใ2ใ3ใพใใฏ4ใฎๅฏไฝ็จใ็ต้จใใใๆฌ็บๆ1027ใพใใฏ1028ใฎๆนๆณใ
[ๆฌ็บๆ1030]
ๅ่จๅฏพ่ฑกใใใใใจ่จบๆญใใใฆใใใๆฌ็บๆ1023ใ1029ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1031]
ๅ่จใใใ่บใใใๅ็ซ่ บใใใๅตๅทฃใใใ็ฒพๅทฃใใใ่ณใฎใใใ่ ่ฝ็ดฐ่่ ซใๅฐๅ ่ ซ็ใ่็ดฐ่่ ซ็ใ้ป่ฒ่ ซใ็ต่ ธใใใ็ด่ ธใใใ่ใใใ้ฃ้ใใใๆฐ็ฎกใใใ้ ญ้ ธ้จใใใ่ตใใใ่ใใใไนณใใใๅญๅฎฎ้ ธใใใใใณๅค้ฐใใใๅซใใๆฌ็บๆ1023ใ1030ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1032]
ๅ่จใใใ้ป่ฒ่ ซใพใใฏไนณใใใๅซใใๆฌ็บๆ1031ใฎๆนๆณใ
[ๆฌ็บๆ1033]
ๅ่จใใใ้่กๆถฒ็ณปใงใใใๆฌ็บๆ1001ใ1030ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1034]
ๅ่จใใใๅบๅฝข่ ซ็ใๅซใใๆฌ็บๆ1023ใ1033ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1035]
่ฟฝๅ ใฎใใๆฒป็ใฎๅฎๆฝใใใใซๅซใใๆฌ็บๆ1023ใ1034ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1036]
ๅ่จ่ฟฝๅ ใฎใใๆฒป็ใๆพๅฐ็ทใใฏใฏใใณๆฅ็จฎใๅๅญฆ็ๆณใ้คๅญT็ดฐ่็ๆณใใตใคใใซใคใณ็ๆณใๆCD47ๆไฝใๆGD2ๆไฝใพใใฏๅ ็ซใขใธใฅใใณใใๅซใใๆฌ็บๆ1035ใฎๆนๆณใ
[ๆฌ็บๆ1037]
ๅ่จ่ฟฝๅ ใฎใใๆฒป็ใMUC-1้ปๅฎณ่ฌใCD40ๆดปๆงๅ่ฌใIDO้ปๅฎณ่ฌใใใณOX86ใขใดใในใใฎใใกใฎ1ใคใพใใฏ่คๆฐใๅซใใๆฌ็บๆ1035ใพใใฏ1036ใฎๆนๆณใ
[ๆฌ็บๆ1038]
ๅ่จ่ฟฝๅ ใฎใใๆฒป็ใใคใณใใญใทใขใใGDC-0919ใ1-ใกใใซ-D-ใใชใใใใกใณใใใซใใซใใณๅกฉ้ ธๅกฉใใใซใใซใใณใCAY10581ใINCB024360ใใใณ2-ใใณใธใซ-2-ใใชใใฝใคใๅฐฟ็ด ๅกฉ้ ธๅกฉใฎใใกใฎ1ใคใพใใฏ่คๆฐใๅซใใๆฌ็บๆ1037ใฎๆนๆณใ
[ๆฌ็บๆ1039]
็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ2ใฎๅ ็ซ็ๆณ็จๆไฝใฎๆไธใใใใซๅซใใๆฌ็บๆ1023ใ1038ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1040]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใฎๆไธใจECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-L1ๆไฝใฎๆไธใๅซใใๆฌ็บๆ1039ใฎๆนๆณใ
[ๆฌ็บๆ1041]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใฎๆไธใจECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-1ๆไฝใฎๆไธใๅซใใๆฌ็บๆ1039ใฎๆนๆณใ
[ๆฌ็บๆ1042]
ๅ่จ่ฟฝๅ ใฎใใๆฒป็ใฎๆๅนๆงใใๅ่จ็ตๆ็ฉใชใใงใฎ่ฉฒ่ฟฝๅ ใฎใใๆฒป็ใฎๅฎๆฝใจๆฏในใฆ้ซใใๆฌ็บๆ1035ใ1038ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1043]
ๅ่จใใใใๅฐใชใใจใ็ฌฌ1ใฎ่ ซ็ใจ็ฌฌ2ใฎ่ ซ็ใๅซใ่ปข็งปใใใงใใใๆฌ็บๆ1023ใ1042ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1044]
ๅ่จ็ตๆ็ฉใ็ฌฌ1ใฎ่ ซ็ใซๅฏพใใฆ่ ซ็ๅจๅฒๆไธใพใใฏ่ ซ็ๅ ๆไธใใใ็ฌฌ2ใฎ่ ซ็ใซๅฏพใใฆใฏ่ ซ็ๅจๅฒๆไธใ่ ซ็ๅ ๆไธใใใใใๅ จ่บซๆไธใใใใชใใๆฌ็บๆ1043ใฎๆนๆณใ
[ๆฌ็บๆ1045]
็ฌฌ2ใฎ่ ซ็ใๆๅนใซๅฆ็ฝฎใใใใๆฌ็บๆ1044ใฎๆนๆณใ
[ๆฌ็บๆ1046]
ๅ่จๅ ็ซ็ๆณ็จๆไฝใฮฑGITRๆไฝใฮฑCD134ๆไฝใพใใฏฮฑCD137ๆไฝใๅซใใๆฌ็บๆ1001ใ1013ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1047]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ2ใฎๅ ็ซ็ๆณ็จๆไฝใใใใณไปปๆใงECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ3ใฎๅ ็ซ็ๆณ็จๆไฝใใใใซๅซใใๆฌ็บๆ1001ใ1013ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1048]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใฮฑGITRๆไฝใECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใฮฑCD134ๆไฝใใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใฮฑCD137ๆไฝใฎใใกใฎๅฐใชใใจใ2ใคใๅซใใๆฌ็บๆ1047ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1049]
ๅ่จใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใTIGITๆไฝใTIM-3ๆไฝใCD47ๆไฝใICOSๆไฝใCD39ๆไฝใBTLAๆไฝใKIRๆไฝใLAG3ๆไฝใพใใฏVISTAๆไฝใๅซใใๆฌ็บๆ1014ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1050]
ๅ่จECM่ฆชๅๆงใใใใใใใณใชใณใใใใใๅซใใๆฌ็บๆ1001ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1051]
ๅ่จใใณใชใณใใใใใSEQ ID NO:16ใๅซใใใใพใใฏSEQ ID NO:16ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใใใใใๅซใใๆฌ็บๆ1050ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1052]
ๅ่จVWFใใใใใSEQ ID NO:14ใๅซใใใใพใใฏSEQ ID NO:14ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใใใใใๅซใใๆฌ็บๆ1006ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1053]
ๆฌ็บๆ1046ใ1052ใฎใใใใใฎ็ตๆ็ฉใๅฏพ่ฑกใซๆไธใใๆฎต้ใๅซใใๅฏพ่ฑกใซใใใใใใๅฆ็ฝฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1054]
็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCD40ใขใดใในใๆไฝใๆไธใใๆฎต้ใๅซใใๆฃ่ ใซใใใใใใๅฆ็ฝฎใใๆนๆณใงใใฃใฆใ่ฉฒๆฃ่ ใๅ ็ซใใงใใฏใใคใณใ็ๆณใซๅฏพใใฆๆตๆๆงใฎใใใๆใใใๆนๆณใ
[ๆฌ็บๆ1055]
ๅ่จๆฃ่ ใใๅ ็ซใใงใใฏใใคใณใ็ๆณใซๆตๆๆงใงใใใใจใใใใฃใฆใใใใใจ่จบๆญใใใฆใใใๆฌ็บๆ1054ใฎๆนๆณใ
[ๆฌ็บๆ1056]
ๅ่จๆฃ่ ใๅ ็ซใใงใใฏใใคใณใ็ๆณใไปฅๅใซๅใใใใจใใใใๆฌ็บๆ1054ใพใใฏ1055ใฎๆนๆณใ
[ๆฌ็บๆ1057]
ๅ่จใใใๅ่จๅ ็ซใใงใใฏใใคใณใ็ๆณใซๆตๆๆงใงใใฃใใๆฌ็บๆ1056ใฎๆนๆณใ
[ๆฌ็บๆ1001]
็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใๅ ็ซ็ๆณ็จๆไฝใๅซใ็ตๆ็ฉใ
[ๆฌ็บๆ1002]
ๅ่จECM่ฆชๅๆงใใใใใ่็คๅขๆฎๅ ๅญ-2๏ผPlGF-2๏ผใซ็ฑๆฅใใใใใใใๅซใใๆฌ็บๆ1001ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1003]
ๅ่จใใใใใSEQ ID NO:1ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใๆฌ็บๆ1002ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1004]
ๅ่จใใใใใSEQ ID NO:1ใๅซใใๆฌ็บๆ1002ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1005]
ๅ่จใใใใใใใฉใณใปใดใฃใฌใใฉใณใๅ ๅญ๏ผVWF๏ผใใใใใๅซใใๆฌ็บๆ1001ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1006]
ๅ่จVWFใใใใใVWF A1ใพใใฏA3ใใใใใงใใใๆฌ็บๆ1005ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1007]
ๅ่จVWFใใใใใSEQ ID NO:3ใSEQ ID NO:11ใพใใฏใใใใฎๆญ็ใจๅฐใชใใจใ85๏ผ ๅไธใฎใใใใใๅซใใๆฌ็บๆ1006ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1008]
ๅ่จVWFใใใใใSEQ ID NO:3ใพใใฏSEQ ID NO:11ใๅซใใๆฌ็บๆ1007ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1009]
ๅ่จใใใใใCXCL-12ใใใใใๅซใใๆฌ็บๆ1001ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1010]
ๅ่จCXCL-12ใใใใใCXCL-12ฮณใใใใใๅซใใๆฌ็บๆ1009ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1011]
ๅ่จใใใใใSEQ ID NO:2ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใๆฌ็บๆ1010ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1012]
ๅ่จใใใใใๅ่จๆไฝใจๅ ฑๆ็ตๅใใฆใใใๆฌ็บๆ1001ใ1011ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1013]
ๅ่จใใใใใไบๅฎ่ฝๆงใชใณใซใผใซใใฃใฆๅ่จๆไฝใซๆถๆฉใใใฆใใใๆฌ็บๆ1001ใ1012ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1014]
ๅ่จๅ ็ซ็ๆณ็จๆไฝใๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใๅซใใๆฌ็บๆ1001ใ1013ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1015]
ๅ่จๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใCTLA4ๆไฝใPD-L1ๆไฝใพใใฏPD-1ๆไฝใๅซใใๆฌ็บๆ1014ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1016]
ๅ่จๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใใใณใใญใชใบใใใใใใซใใใใขใใพใชใบใใใใคใใชใ ใใใใใฌใกใชใ ใใใใขใใซใใใพใใฏใใฅใซใใซใใใๅซใใๆฌ็บๆ1014ใพใใฏ1015ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1017]
ๅ่จๅ ็ซ็ๆณ็จๆไฝใCD-40ใขใดใในใๆไฝใๅซใใๆฌ็บๆ1001ใ1013ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1018]
ๅ่จๆไฝใใใๅๆไฝใงใใใๆฌ็บๆ1001ใ1017ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1019]
ใใใใๅฏพๆไฝใฎๆฏใ็ด1:1ใ10:1ใงใใใๆฌ็บๆ1001ใ1018ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1020]
็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ2ใฎๅ ็ซ็ๆณ็จๆไฝใใใใซๅซใใๆฌ็บๆ1001ใ1019ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1021]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-L1ๆไฝใๅซใใๆฌ็บๆ1020ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1022]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-1ๆไฝใๅซใใๆฌ็บๆ1020ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1023]
ๆฌ็บๆ1001ใ1022ใฎใใใใใฎ็ตๆ็ฉใๅฏพ่ฑกใซๆไธใใๆฎต้ใๅซใใๅฏพ่ฑกใซใใใใใใๅฆ็ฝฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1024]
ๅ่จ็ตๆ็ฉใๅ จ่บซๆไธใใใใใใพใใฏ่ ซ็ๅ ๆณจๅฐใ่ ซ็ๅจๅฒๆณจๅฐใๅ่ๅ ๆณจๅฐใใใใฏ็ตใซใใผใใซๆณจๅฐใซใใฃใฆๆไธใใใใๆฌ็บๆ1023ใฎๆนๆณใ
[ๆฌ็บๆ1025]
ๅ่จใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใๅ่จๆไฝใฎๆไธ้ใใ่ฉฒใใใใใชใใงๆไธใใใ่ฉฒๆไฝใฎๆๅฐๆๅน้ใใๅฐใชใใๆฌ็บๆ1023ใพใใฏ1024ใฎๆนๆณใ
[ๆฌ็บๆ1026]
ๅ่จใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใๅ่จๆไฝใฎๆไธ้ใใ่ฉฒใใใใใชใใงๆไธใใใ่ฉฒๆไฝใฎๆๅฐๆๅน้ใใๅฐใชใใจใ10๏ผ ๅฐใชใใๆฌ็บๆ1025ใฎๆนๆณใ
[ๆฌ็บๆ1027]
ๆฃ่ ใใใใๅ ็ซ็ๆณ่ฌใงไปฅๅใซๅฆ็ฝฎใใใใใจใใใใๆฌ็บๆ1023ใ1026ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1028]
ไปฅๅใฎใใๅ ็ซ็ๆณ่ฌใใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใๅซใใใฎใงใใฃใใๆฌ็บๆ1027ใฎๆนๆณใ
[ๆฌ็บๆ1029]
ๅ่จๅฏพ่ฑกใใไปฅๅใฎใใๅ ็ซ็ๆณ่ฌใซใใใฐใฌใผใ2ใ3ใพใใฏ4ใฎๅฏไฝ็จใ็ต้จใใใๆฌ็บๆ1027ใพใใฏ1028ใฎๆนๆณใ
[ๆฌ็บๆ1030]
ๅ่จๅฏพ่ฑกใใใใใจ่จบๆญใใใฆใใใๆฌ็บๆ1023ใ1029ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1031]
ๅ่จใใใ่บใใใๅ็ซ่ บใใใๅตๅทฃใใใ็ฒพๅทฃใใใ่ณใฎใใใ่ ่ฝ็ดฐ่่ ซใๅฐๅ ่ ซ็ใ่็ดฐ่่ ซ็ใ้ป่ฒ่ ซใ็ต่ ธใใใ็ด่ ธใใใ่ใใใ้ฃ้ใใใๆฐ็ฎกใใใ้ ญ้ ธ้จใใใ่ตใใใ่ใใใไนณใใใๅญๅฎฎ้ ธใใใใใณๅค้ฐใใใๅซใใๆฌ็บๆ1023ใ1030ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1032]
ๅ่จใใใ้ป่ฒ่ ซใพใใฏไนณใใใๅซใใๆฌ็บๆ1031ใฎๆนๆณใ
[ๆฌ็บๆ1033]
ๅ่จใใใ้่กๆถฒ็ณปใงใใใๆฌ็บๆ1001ใ1030ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1034]
ๅ่จใใใๅบๅฝข่ ซ็ใๅซใใๆฌ็บๆ1023ใ1033ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1035]
่ฟฝๅ ใฎใใๆฒป็ใฎๅฎๆฝใใใใซๅซใใๆฌ็บๆ1023ใ1034ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1036]
ๅ่จ่ฟฝๅ ใฎใใๆฒป็ใๆพๅฐ็ทใใฏใฏใใณๆฅ็จฎใๅๅญฆ็ๆณใ้คๅญT็ดฐ่็ๆณใใตใคใใซใคใณ็ๆณใๆCD47ๆไฝใๆGD2ๆไฝใพใใฏๅ ็ซใขใธใฅใใณใใๅซใใๆฌ็บๆ1035ใฎๆนๆณใ
[ๆฌ็บๆ1037]
ๅ่จ่ฟฝๅ ใฎใใๆฒป็ใMUC-1้ปๅฎณ่ฌใCD40ๆดปๆงๅ่ฌใIDO้ปๅฎณ่ฌใใใณOX86ใขใดใในใใฎใใกใฎ1ใคใพใใฏ่คๆฐใๅซใใๆฌ็บๆ1035ใพใใฏ1036ใฎๆนๆณใ
[ๆฌ็บๆ1038]
ๅ่จ่ฟฝๅ ใฎใใๆฒป็ใใคใณใใญใทใขใใGDC-0919ใ1-ใกใใซ-D-ใใชใใใใกใณใใใซใใซใใณๅกฉ้ ธๅกฉใใใซใใซใใณใCAY10581ใINCB024360ใใใณ2-ใใณใธใซ-2-ใใชใใฝใคใๅฐฟ็ด ๅกฉ้ ธๅกฉใฎใใกใฎ1ใคใพใใฏ่คๆฐใๅซใใๆฌ็บๆ1037ใฎๆนๆณใ
[ๆฌ็บๆ1039]
็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ2ใฎๅ ็ซ็ๆณ็จๆไฝใฎๆไธใใใใซๅซใใๆฌ็บๆ1023ใ1038ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1040]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใฎๆไธใจECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-L1ๆไฝใฎๆไธใๅซใใๆฌ็บๆ1039ใฎๆนๆณใ
[ๆฌ็บๆ1041]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใฎๆไธใจECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-1ๆไฝใฎๆไธใๅซใใๆฌ็บๆ1039ใฎๆนๆณใ
[ๆฌ็บๆ1042]
ๅ่จ่ฟฝๅ ใฎใใๆฒป็ใฎๆๅนๆงใใๅ่จ็ตๆ็ฉใชใใงใฎ่ฉฒ่ฟฝๅ ใฎใใๆฒป็ใฎๅฎๆฝใจๆฏในใฆ้ซใใๆฌ็บๆ1035ใ1038ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1043]
ๅ่จใใใใๅฐใชใใจใ็ฌฌ1ใฎ่ ซ็ใจ็ฌฌ2ใฎ่ ซ็ใๅซใ่ปข็งปใใใงใใใๆฌ็บๆ1023ใ1042ใฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1044]
ๅ่จ็ตๆ็ฉใ็ฌฌ1ใฎ่ ซ็ใซๅฏพใใฆ่ ซ็ๅจๅฒๆไธใพใใฏ่ ซ็ๅ ๆไธใใใ็ฌฌ2ใฎ่ ซ็ใซๅฏพใใฆใฏ่ ซ็ๅจๅฒๆไธใ่ ซ็ๅ ๆไธใใใใใๅ จ่บซๆไธใใใใชใใๆฌ็บๆ1043ใฎๆนๆณใ
[ๆฌ็บๆ1045]
็ฌฌ2ใฎ่ ซ็ใๆๅนใซๅฆ็ฝฎใใใใๆฌ็บๆ1044ใฎๆนๆณใ
[ๆฌ็บๆ1046]
ๅ่จๅ ็ซ็ๆณ็จๆไฝใฮฑGITRๆไฝใฮฑCD134ๆไฝใพใใฏฮฑCD137ๆไฝใๅซใใๆฌ็บๆ1001ใ1013ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1047]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ2ใฎๅ ็ซ็ๆณ็จๆไฝใใใใณไปปๆใงECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ3ใฎๅ ็ซ็ๆณ็จๆไฝใใใใซๅซใใๆฌ็บๆ1001ใ1013ใฎใใใใใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1048]
ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใฮฑGITRๆไฝใECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใฮฑCD134ๆไฝใใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใฮฑCD137ๆไฝใฎใใกใฎๅฐใชใใจใ2ใคใๅซใใๆฌ็บๆ1047ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1049]
ๅ่จใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใTIGITๆไฝใTIM-3ๆไฝใCD47ๆไฝใICOSๆไฝใCD39ๆไฝใBTLAๆไฝใKIRๆไฝใLAG3ๆไฝใพใใฏVISTAๆไฝใๅซใใๆฌ็บๆ1014ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1050]
ๅ่จECM่ฆชๅๆงใใใใใใใณใชใณใใใใใๅซใใๆฌ็บๆ1001ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1051]
ๅ่จใใณใชใณใใใใใSEQ ID NO:16ใๅซใใใใพใใฏSEQ ID NO:16ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใใใใใๅซใใๆฌ็บๆ1050ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1052]
ๅ่จVWFใใใใใSEQ ID NO:14ใๅซใใใใพใใฏSEQ ID NO:14ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใใใใใๅซใใๆฌ็บๆ1006ใฎ็ตๆ็ฉใ
[ๆฌ็บๆ1053]
ๆฌ็บๆ1046ใ1052ใฎใใใใใฎ็ตๆ็ฉใๅฏพ่ฑกใซๆไธใใๆฎต้ใๅซใใๅฏพ่ฑกใซใใใใใใๅฆ็ฝฎใใใใใฎๆนๆณใ
[ๆฌ็บๆ1054]
็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCD40ใขใดใในใๆไฝใๆไธใใๆฎต้ใๅซใใๆฃ่ ใซใใใใใใๅฆ็ฝฎใใๆนๆณใงใใฃใฆใ่ฉฒๆฃ่ ใๅ ็ซใใงใใฏใใคใณใ็ๆณใซๅฏพใใฆๆตๆๆงใฎใใใๆใใใๆนๆณใ
[ๆฌ็บๆ1055]
ๅ่จๆฃ่ ใใๅ ็ซใใงใใฏใใคใณใ็ๆณใซๆตๆๆงใงใใใใจใใใใฃใฆใใใใใจ่จบๆญใใใฆใใใๆฌ็บๆ1054ใฎๆนๆณใ
[ๆฌ็บๆ1056]
ๅ่จๆฃ่ ใๅ ็ซใใงใใฏใใคใณใ็ๆณใไปฅๅใซๅใใใใจใใใใๆฌ็บๆ1054ใพใใฏ1055ใฎๆนๆณใ
[ๆฌ็บๆ1057]
ๅ่จใใใๅ่จๅ ็ซใใงใใฏใใคใณใ็ๆณใซๆตๆๆงใงใใฃใใๆฌ็บๆ1056ใฎๆนๆณใ
Claims (15)
- ็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใๅ ็ซ็ๆณ็จๆไฝใๅซใ็ตๆ็ฉใ
- (a)ๅ่จECM่ฆชๅๆงใใใใใ่็คๅขๆฎๅ ๅญ-2๏ผPlGF-2๏ผใซ็ฑๆฅใใใใใใใๅซใฟใไปปๆใงใ่ฉฒใใใใใSEQ ID NO:1ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใใใใใฏ่ฉฒใใใใใSEQ ID NO:1ใๅซใ๏ผใพใใฏ
(b)ๅ่จใใใใใใใฉใณใปใดใฃใฌใใฉใณใๅ ๅญ๏ผVWF๏ผใใใใใๅซใฟใไปปๆใงใ่ฉฒVWFใใใใใVWF A1ใใใใฏA3ใใใใใงใใใใใใซไปปๆใงใ่ฉฒVWFใใใใใSEQ ID NO:3ใSEQ ID NO:11ใใใใฏใใใใฎๆญ็ใจๅฐใชใใจใ85๏ผ ๅไธใฎใใใใใๅซใฟใใใใซไปปๆใง่ฉฒVWFใใใใใSEQ ID NO:3ใใใใฏSEQ ID NO:11ใๅซใ๏ผใพใใฏ
(c)ๅ่จใใใใใCXCL-12ใใใใใๅซใฟใไปปๆใงใ่ฉฒCXCL-12ใใใใใCXCL-12ฮณใใใใใๅซใฟใใใใซไปปๆใงใ่ฉฒใใใใใSEQ ID NO:2ใจๅฐใชใใจใ85๏ผ ๅไธใงใใ๏ผใใใณ๏ผใพใใฏ
(d)ๅ่จใใใใใๅ่จๆไฝใจๅ ฑๆ็ตๅใใฆใใ๏ผใใใณ๏ผใพใใฏ
(e)ๅ่จใใใใใไบๅฎ่ฝๆงใชใณใซใผใซใใฃใฆๅ่จๆไฝใซๆถๆฉใใใฆใใ๏ผใใใณ๏ผใพใใฏ
(f)ๅ่จๅ ็ซ็ๆณ็จๆไฝใๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใๅซใฟใไปปๆใงใ่ฉฒๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใใCTLA4ๆไฝใPD-L1ๆไฝใใใใฏPD-1ๆไฝใๅซใฟใใใค๏ผใพใใฏ่ฉฒๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใใใใณใใญใชใบใใใใใใซใใใใขใใพใชใบใใใใคใใชใ ใใใใใฌใกใชใ ใใใใขใใซใใใใใใใฏใใฅใซใใซใใใๅซใ๏ผใใใณ๏ผใพใใฏ
(g)ๅ่จๅ ็ซ็ๆณ็จๆไฝใCD-40ใขใดใในใๆไฝใๅซใ๏ผใพใใฏ
(h)ๅ่จๆไฝใใใๅๆไฝใงใใ๏ผใใใณ๏ผใพใใฏ
(i)ใใใใๅฏพๆไฝใฎๆฏใ็ด1:1ใ10:1ใงใใ๏ผใใใณ๏ผใพใใฏ
(j)็ตๆ็ฉใใ็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ2ใฎๅ ็ซ็ๆณ็จๆไฝใใใใซๅซใฟใไปปๆใงใECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-L1ๆไฝใๅซใใใใใใฏECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-1ๆไฝใๅซใใ
่ซๆฑ้ 1่จ่ผใฎ็ตๆ็ฉใ - ่ซๆฑ้ 1ใพใใฏ2่จ่ผใฎ็ตๆ็ฉใๅซใใๅฏพ่ฑกใซใใใใใใๅฆ็ฝฎใใใใใฎๅป่ฌใ
- (a)ๅ จ่บซๆไธ็จใงใใใใใพใใฏ่ ซ็ๅ ๆณจๅฐใ่ ซ็ๅจๅฒๆณจๅฐใๅ่ๅ ๆณจๅฐใใใใฏ็ตใซใใผใใซๆณจๅฐใซใใๆไธ็จใงใใ๏ผใชใใณใซ๏ผใพใใฏ
(b)ๅ่จใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใๅ่จๆไฝใฎๆไธ้ใใ่ฉฒใใใใใชใใงๆไธใใใ่ฉฒๆไฝใฎๆๅฐๆๅน้ใใๅฐใชใใใจใไปปๆใงใ่ฉฒใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ่ฉฒๆไฝใฎๆไธ้ใใ่ฉฒใใใใใชใใงๆไธใใใ่ฉฒๆไฝใฎๆๅฐๆๅน้ใใๅฐใชใใจใ10๏ผ ๅฐใชใใใจใ็นๅพดใจใใ๏ผใชใใณใซ๏ผใพใใฏ
(c)ๅ่จๅฏพ่ฑกใใใใๅ ็ซ็ๆณ่ฌใงไปฅๅใซๅฆ็ฝฎใใใใใจใใใใไปปๆใงใ
ไปฅๅใฎใใๅ ็ซ็ๆณ่ฌใใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใๅซใใใฎใงใใฃใใใใค๏ผใใใใฏ่ฉฒๅฏพ่ฑกใใไปฅๅใฎใใๅ ็ซ็ๆณ่ฌใซใใใฐใฌใผใ2ใ3ใพใใฏ4ใฎๅฏไฝ็จใ็ต้จใใ๏ผใใใณ๏ผใพใใฏ
(d)ๅ่จๅฏพ่ฑกใใใใใจ่จบๆญใใใฆใใ๏ผใชใใณใซ๏ผใพใใฏ
(e)ๅ่จใใใใ่บใใใๅ็ซ่ บใใใๅตๅทฃใใใ็ฒพๅทฃใใใ่ณใฎใใใ่ ่ฝ็ดฐ่่ ซใๅฐๅ ่ ซ็ใ่็ดฐ่่ ซ็ใ้ป่ฒ่ ซใ็ต่ ธใใใ็ด่ ธใใใ่ใใใ้ฃ้ใใใๆฐ็ฎกใใใ้ ญ้ ธ้จใใใ่ตใใใ่ใใใไนณใใใๅญๅฎฎ้ ธใใใใใใณๅค้ฐใใใๅซใใไปปๆใงใ่ฉฒใใใ้ป่ฒ่ ซใพใใฏไนณใใใๅซใใ
่ซๆฑ้ 3่จ่ผใฎๅป่ฌใ - ๅ่จใใใ้่กๆถฒ็ณปใงใใใ่ซๆฑ้ 3ใ4(d)ใฎใใใใไธ้ ่จ่ผใฎๅป่ฌใ
- (a)ๅ่จใใใๅบๅฝข่ ซ็ใๅซใ๏ผใชใใณใซ๏ผใพใใฏ
(b)่ฟฝๅ ใฎใใๆฒป็ใจ็ตใฟๅใใใฆ็จใใใใใใจใ็นๅพดใจใใไปปๆใงใ่ฉฒ่ฟฝๅ ใฎใใๆฒป็ใใๆพๅฐ็ทใใฏใฏใใณๆฅ็จฎใๅๅญฆ็ๆณใ้คๅญT็ดฐ่็ๆณใใตใคใใซใคใณ็ๆณใๆCD47ๆไฝใๆGD2ๆไฝใใใใใฏๅ ็ซใขใธใฅใใณใใๅซใฟใใใค๏ผใพใใฏใ่ฉฒ่ฟฝๅ ใฎใใๆฒป็ใใMUC-1้ปๅฎณ่ฌใCD40ๆดปๆงๅ่ฌใIDO้ปๅฎณ่ฌใใใใณOX86ใขใดใในใใฎใใกใฎ1ใคใใใใฏ่คๆฐใๅซใฟใใใใซไปปๆใงใ่ฉฒ่ฟฝๅ ใฎใใๆฒป็ใใใคใณใใญใทใขใใGDC-0919ใ1-ใกใใซ-D-ใใชใใใใกใณใใใซใใซใใณๅกฉ้ ธๅกฉใใใซใใซใใณใCAY10581ใINCB024360ใใใใณ2-ใใณใธใซ-2-ใใชใใฝใคใๅฐฟ็ด ๅกฉ้ ธๅกฉใฎใใกใฎ1ใคใพใใฏ่คๆฐใๅซใ๏ผใชใใณใซ๏ผใพใใฏ
(c)็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ2ใฎๅ ็ซ็ๆณ็จๆไฝใจ็ตใฟๅใใใฆ็จใใใใใใจใ็นๅพดใจใใไปปๆใงใๅ่จๅป่ฌใใECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-L1ๆไฝใ็ตใฟๅใใใฆใชใใใใใใใฏๅ่จๅป่ฌใใECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCTLA4ๆไฝใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใPD-1ๆไฝใ็ตใฟๅใใใฆใชใใ
่ซๆฑ้ 3ใ5ใฎใใใใไธ้ ่จ่ผใฎๅป่ฌใ - ๅ่จ่ฟฝๅ ใฎใใๆฒป็ใฎๆๅนๆงใใๅ่จๅป่ฌใชใใงใฎ่ฉฒ่ฟฝๅ ใฎใใๆฒป็ใฎๅฎๆฝใจๆฏในใฆ้ซใใ่ซๆฑ้ 6(b)่จ่ผใฎๅป่ฌใ
- ๅ่จใใใใๅฐใชใใจใ็ฌฌ1ใฎ่ ซ็ใจ็ฌฌ2ใฎ่ ซ็ใๅซใ่ปข็งปใใใงใใใไปปๆใงใๅ่จๅป่ฌใ็ฌฌ1ใฎ่ ซ็ใซๅฏพใใฆ่ ซ็ๅจๅฒๆไธใพใใฏ่ ซ็ๅ ๆไธใใใ็ฌฌ2ใฎ่ ซ็ใซๅฏพใใฆใฏ่ ซ็ๅจๅฒๆไธใ่ ซ็ๅ ๆไธใใใใใๅ จ่บซๆไธใใใใชใใใใซ็จใใใใใใจใ็นๅพดใจใใใใใซไปปๆใงใ็ฌฌ2ใฎ่ ซ็ใๆๅนใซๅฆ็ฝฎใใใใ่ซๆฑ้ 3ใ7ใฎใใใใไธ้ ่จ่ผใฎๅป่ฌใ
- (a)ๅ่จๅ ็ซ็ๆณ็จๆไฝใใฮฑGITRๆไฝใฮฑCD134ๆไฝใใใใฏฮฑCD137ๆไฝใๅซใ๏ผใพใใฏ
(b)ECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ2ใฎๅ ็ซ็ๆณ็จๆไฝใใใใณไปปๆใงECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใ็ฌฌ3ใฎๅ ็ซ็ๆณ็จๆไฝใใใใซๅซใฟใไปปๆใงใECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใฮฑGITRๆไฝใECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใฮฑCD134ๆไฝใใใใณECM่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใฮฑCD137ๆไฝใฎใใกใฎๅฐใชใใจใ2ใคใๅซใใ
่ซๆฑ้ 1ใ2(e)ใฎใใใใไธ้ ่จ่ผใฎ็ตๆ็ฉใ - ๅ่จใใงใใฏใใคใณใ้ปๅฎณๆงๆไฝใTIGITๆไฝใTIM-3ๆไฝใCD47ๆไฝใICOSๆไฝใCD39ๆไฝใBTLAๆไฝใKIRๆไฝใLAG3ๆไฝใพใใฏVISTAๆไฝใๅซใใ่ซๆฑ้ 2(f)่จ่ผใฎ็ตๆ็ฉใ
- ๅ่จECM่ฆชๅๆงใใใใใใใณใชใณใใใใใๅซใฟใไปปๆใงใ่ฉฒใใณใชใณใใใใใใSEQ ID NO:16ใๅซใใใพใใฏSEQ ID NO:16ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใใใใใๅซใใ่ซๆฑ้ 1่จ่ผใฎ็ตๆ็ฉใ
- ๅ่จใใใใใVWFใใใใใๅซใฟใ่ฉฒVMFใใใใใVWF A1ใพใใฏA3ใใใใใงใใใใใค่ฉฒVWFใใใใใใSEQ ID NO:14ใๅซใใใพใใฏSEQ ID NO:14ใจๅฐใชใใจใ85๏ผ ๅไธใงใใใใใใใๅซใใ่ซๆฑ้ 1่จ่ผใฎ็ตๆ็ฉใ
- ่ซๆฑ้ 9ใ12ใฎใใใใไธ้ ่จ่ผใฎ็ตๆ็ฉใๅซใใๅฏพ่ฑกใซใใใใใใๅฆ็ฝฎใใใใใฎๅป่ฌใ
- ็ดฐ่ๅคใใใชใใฏใน๏ผECM๏ผ่ฆชๅๆงใใใใใซๆฉ่ฝ็ใซ้ฃ็ตใใใCD40ใขใดใในใๆไฝใๅซใใๆฃ่ ใซใใใใใใๅฆ็ฝฎใใใใใฎๅป่ฌใงใใฃใฆใ่ฉฒๆฃ่ ใๅ ็ซใใงใใฏใใคใณใ็ๆณใซๅฏพใใฆๆตๆๆงใฎใใใๆใใใๅป่ฌใ
- (a)ๅ่จๆฃ่ ใใๅ ็ซใใงใใฏใใคใณใ็ๆณใซๆตๆๆงใงใใใใจใใใใฃใฆใใใใใจ่จบๆญใใใฆใใ๏ผใใใณ๏ผใพใใฏ
(b)ๅ่จๆฃ่ ใๅ ็ซใใงใใฏใใคใณใ็ๆณใไปฅๅใซๅใใใใจใใใใไปปๆใงใๅ่จใใใ่ฉฒๅ ็ซใใงใใฏใใคใณใ็ๆณใซๆตๆๆงใงใใฃใใ
่ซๆฑ้ 14่จ่ผใฎๅป่ฌใ
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| EP (1) | EP3612209A4 (ja) |
| JP (2) | JP7419070B2 (ja) |
| CN (1) | CN111132693A (ja) |
| AU (2) | AU2018256453B2 (ja) |
| MX (1) | MX2019012579A (ja) |
| WO (1) | WO2018195386A1 (ja) |
Families Citing this family (6)
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| CN108623686A (zh) | 2017-03-25 | 2018-10-09 | ไฟก่พพ็็ฉๅถ่ฏ(่ๅท)ๆ้ๅ ฌๅธ | ๆox40ๆไฝๅๅ ถ็จ้ |
| WO2019094938A2 (en) | 2017-11-13 | 2019-05-16 | The University Of Chicago | Methods and compositions for the treatment of wounds |
| EP3762407A4 (en) * | 2018-03-05 | 2021-11-24 | The University of Chicago | METHODS AND COMPOSITIONS FOR TREATMENT OF CANCER WITH ECM AFFINITY PEPTIDES BONDED TO CYTOKINE |
| MX2021000155A (es) * | 2018-07-03 | 2021-05-12 | Catalent Pharma Solutions Llc | Moleculas de proteina multifuncionales que comprenden decorina y su uso. |
| EP3930687A4 (en) * | 2019-02-25 | 2023-06-07 | The University of Chicago | METHODS AND COMPOSITIONS FOR THE TREATMENT OF INFLAMMATORY AND AUTOIMMUNE CONDITIONS USING ECM AFFINITY PEPTIDES LINKED TO ANTI-INFLAMMATORY AGENTS |
| MX2021014867A (es) * | 2019-06-03 | 2022-03-25 | Univ Chicago | Metodos y composiciones para el tratamiento del cancer con adyuvantes dirigidos al cancer. |
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|---|---|---|---|---|
| US5654270A (en) | 1988-06-28 | 1997-08-05 | La Jolla Cancer Research Foundation | Use of fibromodulin to prevent or reduce dermal scarring |
| WO2001016180A2 (en) | 1999-08-27 | 2001-03-08 | Board Of Regents, The University Of Texas System | Cd40 agonist compositions and methods of use |
| KR20030060772A (ko) | 2000-05-05 | 2003-07-16 | ์งํฐ์จ๋ฐ์ด์ค์๋ผํจํฑ์ค,์ธํฌ. | ํ์ง์ ํ๋ฒ์ผ๋ก ์์ฑ๋ ๋ฐ์ฝ๋ฆฐ |
| US20080160024A1 (en) * | 2006-12-07 | 2008-07-03 | Board Of Trustees Of The University Of Arkansas | Inhibition of cancer metastasis |
| AT504685B1 (de) | 2006-12-20 | 2009-01-15 | Protaffin Biotechnologie Ag | Fusionsproteine |
| CN102648212B (zh) * | 2009-11-13 | 2014-12-03 | ๅบ็ซ็ฆ็ๆณๅ ฌๅธ | ๅ ๅซๅฏ็ปดๅๅธๅ ฐๅพทๅ ๅญ(vWF)็ๅถๅๅๅ ถ็ธๅ ณๅถๅคๆนๆณใ่ฏๅ็ๅ็จ้ |
| US9879062B2 (en) | 2012-07-03 | 2018-01-30 | Ecole Polytechnique Federale De Lausanne | Protein-binding peptide isolated from placenta growth factor |
| US10420820B2 (en) | 2014-09-29 | 2019-09-24 | Counterpoint Biomedia LLC | Targeting of pharmaceutical agents to pathologic areas using bifunctional fusion polypeptides |
| WO2016054555A2 (en) | 2014-10-03 | 2016-04-07 | Novartis Ag | Combination therapies |
| US10682390B2 (en) | 2015-07-16 | 2020-06-16 | Biokine Therapeutics Ltd. | Compositions and methods for treating cancer |
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2018
- 2018-04-20 EP EP18787963.0A patent/EP3612209A4/en active Pending
- 2018-04-20 US US16/606,539 patent/US11574747B2/en active Active
- 2018-04-20 AU AU2018256453A patent/AU2018256453B2/en active Active
- 2018-04-20 WO PCT/US2018/028505 patent/WO2018195386A1/en unknown
- 2018-04-20 CN CN201880041832.4A patent/CN111132693A/zh active Pending
- 2018-04-20 JP JP2019557434A patent/JP7419070B2/ja active Active
- 2018-04-20 MX MX2019012579A patent/MX2019012579A/es unknown
-
2023
- 2023-02-03 US US18/164,164 patent/US20230377764A1/en active Pending
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2024
- 2024-01-10 JP JP2024001630A patent/JP2024041874A/ja active Pending
- 2024-05-02 AU AU2024202918A patent/AU2024202918A1/en active Pending
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