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Continuous precipitation for monoclonal antibody capture using countercurrent washing by microfiltration

机译：使用微滤逆流洗涤的单克隆抗体捕获连续沉淀

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Abstract > There is renewed interest in the possibility of using precipitation for initial capture of high‐value therapeutic proteins as part of an integrated continuous downstream process. Precipitation is greatly facilitated by the high product titers now achieved in most cell culture processes, in sharp contrast to chromatographic processes whose performance is reduced at high titers. The current study used a combination of reversible cross‐linking (zinc chloride, ZnCl <sub>2</sub> ) and volume exclusion (polyethylene glycol) agents to precipitate a monoclonal antibody product directly from harvested cell culture fluid using a continuous tubular precipitation reactor. The precipitates were then dewatered and continuously washed using tangential flow filtration, with a countercurrent‐staged configuration used to reduce the amount of wash buffer required and increase host cell protein removal. Long‐term operation was achieved by operating the membrane modules below the critical filtrate flux to avoid fouling. Experimental results demonstrate the feasibility of this fully continuous integrated precipitation process at bench scale, with design calculations used to explore the key factors affecting the performance of this system for initial antibody capture. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> > 对使用沉淀用于初始捕获高价值治疗蛋白的可能性的可能性重新进行了兴趣，作为集成连续下游过程的一部分。通过在大多数细胞培养方法中实现的高产物滴度大大促进了沉淀，其与色谱过程鲜明对比，其性能在高滴度下降低。目前的研究用来了可逆交联（氯化锌，ZnCl <sub> 2 </ sub> ）和体积排除（聚乙二醇）试剂使用连续管状沉淀反应器直接从收获的细胞培养物中沉淀单克隆抗体产物。然后将沉淀物脱水并使用切向流过滤连续洗涤，其用于减少所需洗涤缓冲液的量并增加宿主细胞蛋白质去除的逆流阶段。通过在低于临界滤液通量以下操作膜模块来实现长期操作，以避免污垢。实验结果表明，这种完全连续的综合降水过程在板凳上的可行性，设计计算用于探讨影响该系统的初始抗体捕获性能的关键因素。 </ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-15005/'>《Biotechnology Progress》</a> <b style="margin: 0 2px;">|</b><span>2019年第6期</span><b style="margin: 0 2px;">|</b><span>共8页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Li Zhao&option=202" target="_blank" rel="nofollow">Li Zhao;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Gu Qin&option=202" target="_blank" rel="nofollow">Gu Qin;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Coffman Jonathan L.&option=202" target="_blank" rel="nofollow">Coffman Jonathan L.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Przybycien Todd&option=202" target="_blank" rel="nofollow">Przybycien Todd;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zydney Andrew L.&option=202" target="_blank" rel="nofollow">Zydney Andrew L.;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Department of Chemical EngineeringThe Pennsylvania State UniversityPennsylvania;</p> <p>Department of Chemical EngineeringCarnegie Mellon UniversityPittsburgh Pennsylvania;</p> <p>Boehringer Ingelheim Pharmaceuticals Inc.Fremont California;</p> <p>Department of Chemical EngineeringCarnegie Mellon UniversityPittsburgh Pennsylvania;</p> <p>Department of Chemical EngineeringThe Pennsylvania State UniversityPennsylvania;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/15.html" title="生物科学">生物科学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=antibody&option=203" rel="nofollow">antibody;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=continuous processing&option=203" rel="nofollow">continuous processing;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=microfiltration&option=203" rel="nofollow">microfiltration;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=precipitation&option=203" rel="nofollow">precipitation;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=staging&option=203" rel="nofollow">staging;</a> </p> <div class="translation"> 机译：抗体;连续加工;微滤;降水;分期; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li >中文文献</li> <li >专利</li> </ul> </div> <div class="similarity_details"> <ul > <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/0704021880479.html">Continuous precipitation for monoclonal antibody capture using countercurrent washing by microfiltration</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Li Zhao&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Li Zhao,</a> <a 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</li> <li> <div> <b>6. </b><a class="enjiyixqcontent" href="/academic-conference-cn_meeting-729_thesis/020221811425.html">PAC四级逆流吸附-微滤组合工艺处理二级出水的实验探究</a> <b>[C]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李竞&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 李竞</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=顾平&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,顾平</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=张光辉&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,张光辉</a> <span> <a href="/conference-cn-729/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 中国土木工程学会全国排水委员会2015年年会 </a> <span> <span> . 2015</span> </span> </div> </li> <li> <div> <b>7. </b><a class="enjiyixqcontent" href="/academic-degree-domestic_mphd_thesis/020315993726.html">逆流吸附-混凝-微滤处理铯污染水的中试</a> <b>[A] </b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=郭美彤&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 郭美彤</a> <span> . 2018</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/06120212244321.html">一种洗涤抽滤装置及微/纳米颗粒连续抽滤洗涤装置</a> <b>[P]</b> . <span> 中国专利： CN212238394U </span> <span> . 2020-12-29</span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06120110848612.html">稀土沉淀的逆流洗涤装置及使用该装置的稀土草酸沉淀母液和洗液回用的方法</a> <b>[P]</b> . <span> 中国专利： CN108342574A </span> <span> . 2018-07-31</span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130442505601.html">Variant of an immunointeractive molecule, monoclonal antibody, de-immunized form of monoclonal antibody 3b6, method for generating a de-immunized monoclonal antibody, de-immunized antibody molecule, de-immunized antibody, murine monoclonal antibody variant 3b6 de-immunized, variant of a murine monoclonal antibody 3b6 de-immunized for use in humans, method for detecting a blood clot in a human patient, method for detecting a blood clot or an antigen-binding fragment, method for facilitating the dissolution or removal of a blood clot in a human, use of a murine variant-derived monoclonal antibody, and, conjugated</a> <b>[P]</b> . <span> 外国专利：  BR0210648A </span> <span> . 2004-10-05</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：免疫相互作用分子的变体，单克隆抗体，单克隆抗体3b6的去免疫形式，产生去免疫的单克隆抗体，去免疫的抗体分子，去免疫的抗体，鼠源单克隆抗体变体3b6的去免疫形式，用于人的免疫接种的鼠单克隆抗体3b6，检测人类患者血液凝块的方法，检测血液凝块或抗原结合片段的方法，促进血液凝块溶解或去除的方法人类，使用鼠源变异鼠单克隆抗体，并偶联 </span> </p> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/patent-detail/06130406764946.html">isolated monoclonal antibodies; monoclonal antibodies or antigen binding fragments thereof; composition; isolated polynucleotide molecules; recombinant polypeptide; polypeptides; host cell; method of making an antibody; use of an agent for treating cancer in a patient; uses of monoclonal antibody or antigen-binding fragment thereof for the treatment of a subject suffering from cancer; use of monoclonal antibody to treat a subject suffering from cancer; a composition comprising an agr2 binding antibody; a composition comprising a c4.4a binding antibody; a composition comprising an agr2 binding antibody and a c4.4a binding antibody; composition comprising an antibody; use of an agr2 binding antibody; use of a c4.4a binding antibody; use of an antibody; and kit comprising an antibody</a> <b>[P]</b> . <span> 外国专利：  BR112017004510A8 </span> <span> . 2018-06-26</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：分离的单克隆抗体;单克隆抗体或其抗原结合片段;组成;分离的多核苷酸分子;重组多肽多肽;宿主细胞;制备抗体的方法;药剂用于治疗患者的癌症的用途;单克隆抗体或其抗原结合片段在治疗癌症患者中的用途;单克隆抗体在治疗患有癌症的受试者中的用途;包含agr2结合抗体的组合物;包含c4.4a结合抗体的组合物;包含agr2结合抗体和c4.4a结合抗体的组合物;包含抗体的组合物;使用agr2结合抗体;使用c4.4a结合抗体;抗体的使用;和包含抗体的试剂盒 </span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/patent-detail/06130406764947.html">isolated monoclonal antibodies; monoclonal antibodies or antigen binding fragments thereof; composition; isolated polynucleotide molecules; recombinant polypeptide; polypeptides; host cell; method of making an antibody; use of an agent for treating cancer in a patient; uses of monoclonal antibody or antigen-binding fragment thereof for the treatment of a subject suffering from cancer; use of monoclonal antibody to treat a subject suffering from cancer; a composition comprising an agr2 binding antibody; a composition comprising a c4.4a binding antibody; a composition comprising an agr2 binding antibody and a c4.4a binding antibody; composition comprising an antibody; use of an agr2 binding antibody; use of a c4.4a binding antibody; use of an antibody; and kit comprising an antibody</a> <b>[P]</b> . <span> 外国专利：  BR112017004510A2 </span> <span> . 2018-01-23</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：分离的单克隆抗体;单克隆抗体或其抗原结合片段;组成;分离的多核苷酸分子;重组多肽多肽;宿主细胞;制备抗体的方法;药剂用于治疗患者的癌症的用途;单克隆抗体或其抗原结合片段在治疗癌症患者中的用途;单克隆抗体在治疗患有癌症的受试者中的用途;包含agr2结合抗体的组合物;包含c4.4a结合抗体的组合物;包含agr2结合抗体和c4.4a结合抗体的组合物;包含抗体的组合物;使用agr2结合抗体;使用c4.4a结合抗体;抗体的使用;和包含抗体的试剂盒 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> <div class="right rightcon"> <div class="details_img cardcommon clearfix" style="margin-bottom: 10px;display:none;" > </div> </div> </div> <div id="thesis_get_original1" 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