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CONJUGATES OF LABELED RADIOACTIVE ZIRCONIUM DESIGNED ANTIBODIES WITH CYSTEINE REPLACEMENTS
专利权人:
ДЖЕНЕНТЕК; ИНК. (US)
发明人:
ДЖИЛЛ Херман (US),ДЖУНУТУЛА Джагатх Р. (US),ЛОУМЭН Генри Б. (US),МАРИК Ян (US),ТИНИАНОУ Джефф (US),УИЛЛЬЯМС Саймон (US)
申请号:
RU2012123007/10
公开号:
RU2012123007A
申请日:
2010.11.04
申请国别(地区):
RU
年份:
2013
代理人:
摘要:
1. Labeled with zirconium, engineered antibody with cysteine substitutions, containing engineered antibody with cysteine substitutions (Ab), conjugated through a free amino acid cysteine with a linker (L) and a zirconium complex (Z) having the formula I: where p is 1-4.2. Zirconium-labeled, engineered antibody with cysteine substitutions according to claim 1, where p represents 2.3. Zirconium-labeled, engineered antibody with cysteine substitutions according to claim 1, where the engineered antibody with cysteine substitutions in the heavy chain contains a sequence selected from SEQ ID NO: 11, 12, 13 and 15: where cysteine is in SEQ ID NO: 11, 12, 13 and 15 represents the free amino acid cysteine. 4. Zirconium-labeled, engineered antibody with cysteine substitutions according to claim 1, where the engineered antibody with cysteine substitutions in the light chain contains a sequence selected from SEQ ID NO: 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 , 27, 45 and 46: where cysteine in SEQ ID NO: 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 45 and 46 is the free amino acid cysteine. 5. The zirconium-labeled, engineered cysteine-substituted antibody of claim 1, wherein the engineered cysteine-antibody is prepared by a method comprising: (i) mutagenesis of a nucleic acid sequence encoding a engineered cysteine-antibody; (ii) expression of the engineered cysteine-antibody; and (iii) isolation and purification of the engineered antibody with cysteine substitutions. 6. Zirconium-labeled, engineered antibody with cysteine substitutions according to claim 1, where the engineered antibody with cysteine substitutions is selected from a monoclonal antibody, bispecific1. Меченное цирконием, сконструированное антитело с цистеиновыми заменами, содержащее сконструированное антитело с цистеиновыми заменами (Ab), конъюгированное через свободную аминокислоту цистеин с линкером (L) и комплексом циркония (Z), обладающему формулой I:где p представляет собой 1-4.2. Меченное цирконием, сконстру
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