INOTUZUMAB OZOGAMICIN

主成分: INOTUZUMAB OZOGAMICIN (~ 160 kDa)

商品名: BESPONSA

中文名: 沛斯博凍晶注射劑

美國食品藥物管理局首次核准時間與編號: 2017.08.17 [BLA #761040]

歐盟藥品管理局首次核准時間與編號: 2017.06.28 [EMEA/H/C/004119]

研發廠商: PFIZER—WYETH PHARMACEUTICALS藥廠(美國)/PFIZER藥廠(歐盟)

生物製劑序列: (QLVQSGAEVKKPGASVKVSCKASGYRFTNYWIHWVRQAPGQGLEWIGGINPGNNYATYRRKFQGRVTMTADTSTSTVYMELSSLRSEDTAVYYCTREGYGNYGAWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK)*2 + (DVQVTQSPSSLSASVGDRVTITCRSSQSLANSYGNTFLSWYLHKPGKAPQLLIYGISNRFSGVPDRFSGSGSGTDFTLTISSLQPEDFATYYCLQGTHQPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC)*2 + (N-Acetyl-gamma-calicheamicin dimethylhydrazide with a acid-cleavable linker: 4-(4-acetylphenoxy) butanoic acid)*(2~8)

IUPAC名: N-Acetyl-gamma-calicheamicin dimethylhydrazide: S-[(2R,3S,4S,6S)-6-[[(2R,3S,4S,5R,6R)-5-[(2S,4S,5S)-5-[acetyl(ethyl)amino]-4-methoxyoxan-2-yl]oxy-6-[[(2S,5Z,9R,13E)-13-[2-[(4-hydrazinyl-2-methyl-4-oxobutan-2-yl)disulfanyl]ethylidene]-9-hydroxy-12-(methoxycarbonylamino)-11-oxo-2-bicyclo[7.3.1]trideca-1(12),5-dien-3,7-diynyl]oxy]-4-hydroxy-2-methyloxan-3-yl]amino]oxy-4-hydroxy-2-methyloxan-3-yl] 4-[(2S,3R,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyloxan-2-yl]oxy-5-iodo-2,3-dimethoxy-6-methylbenzenecarbothioate 

分子線性簡式(SMILES): N-Acetyl-gamma-calicheamicin dimethylhydrazide: CCN(C1COC(CC1OC)OC2C(C(C(OC2OC3C#CC=CC#CC4(CC(=O)C(=C3C4=CCSSC(C)(C)CC(=O)NN)NC(=O)OC)O)C)NOC5CC(C(C(O5)C)SC(=O)C6=C(C(=C(C(=C6OC)OC)OC7C(C(C(C(O7)C)O)OC)O)I)C)O)O)C(=O)C

公共化合物資料庫(PubChem): 

• Inotuzumab Ozogamicin: 不適用/CAS編號: 635715-01-4

• N-Acetyl-gamma-calicheamicin dimethylhydrazide: 86567977/CAS編號: 136185-00-7

• Ozogamicin: 9942071/CAS編號: 400046-53-9

英文仿單: U.S. FDA英文仿單 ORIG-1；EMA英文仿單 R/0023

給藥途徑: 靜脈輸注(intravenous infusion)

劑量: 0.9 mg凍乾粉 [先與符合美國藥典標準的4毫升室溫無菌注射用水重構，再取3.6毫升重構液與符合美國藥典標準的0.9%氯化鈉注射液稀釋成總體積為50 mL後使用(reconstitute each vial with 4 mL of sterile water for injection, USP, to obtain a concentration of 0.25 mg/mL of BESPONSA that delivers 3.6 mL. Add reconstituted solution to an infusion container with 0.9% Sodium Chloride Injection, USP, to a make a total volume of 50 mL)]

機制: INOTUZUMAB OZOGAMICIN為抗CD22抗體INOTUZUMAB與棘孢小單孢菌(Micromonospora echinospora)產生的calicheamicin類抗生素OZOGAMICIN組成的抗體-藥物複合體(antibody-drug conjugate)，帶有CD22分化群抗原的癌細胞，會因為INOTUZUMAB的結合而將INOTUZUMAB OZOGAMICIN攝入，並使OZOGAMICIN在細胞內釋出，造成雙股DNA斷裂，而誘發細胞週期停滯與細胞凋亡(cell cycle arrest and apoptotic cell death)。

適應症:

1. 血液淋巴惡性腫瘤|急性淋巴母細胞白血病(ALL, acute lymphoblastic leukemia):

用於治療成人的復發或難治性B前驅細胞急性淋巴母細胞白血病(ALL, B-cell precursor acute lymphoblastic leukemia)；

潛在靶點與作用機轉:

• • 分化群抗原(cluster of differentiation)

    1. CD22B淋巴細胞受體(B-cell receptor CD22)

       • 人CD22與抗CD22抗體的視覺化立體交互作用: 5VL3_Epratuzumab (RCSB)、7O52_m971 (RCSB)

  • 己醣基轉移酶(hexosyltransferase)

    1. CALG1卡奇黴素鼠李醣轉移酶(calicheamicin 3'-O-methyl-rhamnosyltransferase CalG1)

       • 棘孢小單孢菌CALG1與OZOGAMICIN類似物的視覺化立體交互作用: 3OTH_CLJ (RCSB)

中華民國藥品許可與健保價格(中文的用法、劑量、副作用等資訊詳見各連結內之仿單資料連結):

• 研發廠:

1. 食品藥物管理署衛部菌疫輸字第001081號之沛斯博凍晶注射劑[美國製]:2018.04.25~2028.04.25, 中央健康保險署藥品代碼KC01081209之健保價格: 新台幣372,081元/1mg