ДЗЕ ГАВЕРМЕНТ ОФ ДЗЕ ЮНАЙТЕД СТЕЙТС ОФ АМЕРИКА ЭЗ РЕПРЕЗЕНТЕД БАЙ ДЗЕ СЕКРЕТАРИ ОФ ДЗЕ ДЕПАРМЕНТ ОФ ХЕЛС ЭНД ХЬЮМАН СЁРВИСЕЗ (US)
发明人:
ПАСТАН Ира Х. (US),ВЕЛДОН Джон (US),БИЭРС Ричард (US)
申请号：
RU2013148919/10
公开号：
RU2013148919A
申请日:
2012.05.04
申请国别(地区):
RU
年份:
2015
代理人:
摘要：
1. A chimeric molecule containing a fusion polypeptide having the formula M-L1-FCS-FL-functional domain III RE, in which M is an antibody that specifically binds to mesothelin, or a fragment thereof that specifically binds to mesothelin； L1 consists of continuous sequences of 1 to 10 amino acid residues； FCS is a furin cleavage site consisting of a continuous sequence of amino acid residues capable of cleaving furin； FL consists of a continuous sequence of 3 to 8 amino acid residues independently selected from glycine and serine； functional domain III PE consists of a continuous sequence of amino acid residues identical to the sequence of SEQ ID NO: 1 from position 395 to position 613, optionally containing (i) a substitution in one or more residues corresponding to residues 609 -613 from SEQ ID NO: 1, (ii) replacing arginine with glycine, alanine, valine, leucine or isoleucine at the position corresponding to position 490 in SEQ ID NO: 1, (iii) replacing one or more residues corresponding to residues of SEQ ID NO: 1, where the residues of SEQ ID NO: 1 support survive the immunogenicity of the epitope or subepitope of domain III RE, or (iv) a combination of any of (i) - (iii) .2. The molecule of claim 1, wherein the antibody is a miniantibody, diabody, triatelo, Fab ′ fragment, F (ab) ′ fragment, Fv single chain protein (“scFv”), or a Fv protein fragment (“dsFv”) stabilized by disulfide bonds. . The molecule of claim 1, wherein the antibody fragment contains disulfide-stabilized variable regions of the light and heavy chains of the immunoglobulin fused to the rest of the molecule by linking the heavy chain to L1.4. M1. Химерная молекула, содержащая слитый полипептид, имеющий формулу M-L1-FCS-FL-функциональный домен III РЕ, в которойМ представляет собой антитело, которое специфически связывается с мезотелином, или его фрагмент, который специфически связывается с мезотелином；L1 состоит из непрерывной последовательности от 1 до 10 аминокислотных остатков；FCS представля
