公开(公告)号：WO2011107518A1

公开(公告)日：2011-09-09

申请号：PCT/EP2011/053126

申请日：2011-03-02

Applicant: BOEHRINGER INGELHEIM INTERNATIONAL GMBH ,  AMBROSIUS, Dorothee ,  DIETERLE, Michael ,  DOBBERTHIEN, Philine ,  HOYER, Maria-Katharina

Inventor： AMBROSIUS, Dorothee ,  DIETERLE, Michael ,  DOBBERTHIEN, Philine ,  HOYER, Maria-Katharina

IPC: C07K14/31 ,  C07K1/32

CPC classification number: C07K1/32 ,  C07K14/31

Abstract: Die Erfindung betrifft ein Verfahren zur selektiven Anreicherung von Immunglobulinen oder anderen Proteinen, die eine Fc-Domäne enthalten (Zielprotein), mit den Schritten: e. Bereitstellen einer Lösung, die das Zielprotein enthält; f. Einbringen eines Fc-bindenden Proteins mit genau zwei Bindungsstellen unter Bedingungen, die eine Bindung ermöglichen; g. Abtrennen des Präzipitates von der flüssigen Phase; h. Lösen der Bindung des Zielproteins von dem Fc-bindenden Protein.

Abstract translation: 本发明涉及一种用于包含Fc结构域（靶蛋白）的免疫球蛋白或其它蛋白质的选择性富集的方法，包括以下步骤：即 提供包含所述靶蛋白的溶液; F。 引进具有允许结合的条件下正好有两个结合位点的Fc结合蛋白; 克 分离从液相中沉淀物; 小时。 从Fc结合蛋白的靶蛋白的释放的结合。

公开(公告)号：WO2010151688A3

公开(公告)日：2010-12-29

申请号：PCT/US2010/039854

申请日：2010-06-24

Applicant: AMGEN INC. ,  SHULTZ, Joseph, Edward ,  HART, Roger

Inventor： SHULTZ, Joseph, Edward ,  HART, Roger

IPC: C07K1/22 ,  C07K1/32 ,  C07K1/18

Abstract: Methods of purifying proteins expressed in non-mammalian expression systems in a non-native soluble form directly from cell lysate are disclosed. Methods of purifying proteins expressed in non-mammalian expression systems in a non-native limited solubility form directly from a refold solution are also disclosed. Resin regeneration methods are also provided.

公开(公告)号：WO2010151632A1

公开(公告)日：2010-12-29

申请号：PCT/US2010/039771

申请日：2010-06-24

Applicant: BRISTOL-MYERS SQUIBB COMPANY ,  ARUNAKUMARI, Alahari ,  WANG, Jue ,  DIEHL, Timothy, Kyle

Inventor： ARUNAKUMARI, Alahari ,  WANG, Jue ,  DIEHL, Timothy, Kyle

IPC: C07K1/32 ,  C07K1/30 ,  C07K16/00

CPC classification number: C07K1/32 ,  C07K1/30 ,  C07K16/00 ,  C07K16/065 ,  C07K2317/14 ,  C07K2317/21

Abstract: The invention provides methods for a purifying protein of interest from a mixture comprising the protein of interest and one or more contaminants, including host cell DNA and proteins, by precipitation of the contaminants with caprylic acid. Such methods are particularly useful for purifying antibodies from cell cultures. Moreover, mixtures that have been depleted of contaminants using the methods of the invention can be used directly in downstream chromatography applications (e.g., ion exchange chromatography) without any further purification. These methods lead to manufacturing processes with a minimum number of unit operations and reduce the resource requirements, and thus positively influence the cost of goods for therapeutic protein production.

Abstract translation: 本发明提供了通过用辛酸沉淀污染物，从包含目标蛋白质和一种或多种污染物（包括宿主细胞DNA和蛋白质）的混合物中纯化目的蛋白质的方法。 这样的方法特别可用于从细胞培养物纯化抗体。 此外，使用本发明的方法已经耗尽污染物的混合物可以直接用于下游色谱应用（例如离子交换色谱法），无需任何进一步的纯化。 这些方法导致制造过程中的单位操作数量最少，并减少资源需求，从而积极影响产品治疗蛋白质生产的成本。

公开(公告)号：WO2010074702A1

公开(公告)日：2010-07-01

申请号：PCT/US2009/006363

申请日：2009-12-02

Applicant: MILLIPORE CORPORATION ,  MOYA, Wilson ,  JABER, Jad

Inventor： MOYA, Wilson ,  JABER, Jad

IPC: C07K1/32

CPC classification number: C07K1/32

Abstract: The present invention relates to a bimodal polymer such as a soluble polymer capable of irreversibly binding to insoluble particulates and a subset of soluble impurities and also capable of reversibly binding to one or more desired biomolecules in an unclarified biological material containing stream and the methods of using such a material to purify one or more desired biomolecules from such a stream without the need for prior clarification. Such a polymer comprises domains of charged pendant groups such as primary, secondary, tertiary or quaternary amines, (first mode) and is rendered insoluble and precipitates out of solution simply upon complexing with oppositely charged solid particulates and a fraction of the soluble impurities in an amount sufficient to form an aggregate that can no longer be held in solution. The polymer further comprises other domains of pendant groups that are charged or uncharged, hydrophilic or hydrophobic or have a ligand that is selective for the biomolecule of interest depending on the process conditions such as pH, ionic strength, salts, and the like (second mode). When present in one mode, such as the uncharged form, said pendant groups are capable of binding to one or more desired biomolecules within the stream (protein, polypeptide, etc) in an unclarified cell broth. The precipitate can then be removed from the stream, such as by being filtered out from the remainder of the stream and the desired biomolecule is recovered such as by selective elution.

Abstract translation: 本发明涉及双峰聚合物，例如能够不可逆地结合不溶性微粒的可溶性聚合物和可溶性杂质的子集，并且还能够在含有未澄清生物材料的流中可逆地结合一种或多种所需的生物分子和使用方法 这种材料从这种流中纯化一种或多种所需的生物分子，而不需要事先澄清。 这样的聚合物包含带电侧基的结构域，例如伯，仲，叔或季胺，（第一模式），并且在与相反电荷的固体颗粒和一部分可溶性杂质的络合中，不溶解并沉淀出溶液， 足以形成不能再溶解的聚集体。 聚合物还包括根据诸如pH，离子强度，盐等的工艺条件，带电荷或不带电荷，亲水或疏水的或具有对感兴趣的生物分子有选择性的配体的侧基的其它结构域（第二模式 ）。 当以一种模式存在时，例如不带电的形式，所述侧基能够与未澄清的细胞液中的流（蛋白质，多肽等）内的一种或多种所需的生物分子结合。 然后可以从流中除去沉淀物，例如通过从其余流中过滤出来，并且通过选择性洗脱来回收所需的生物分子。

公开(公告)号：WO2009082443A2

公开(公告)日：2009-07-02

申请号：PCT/US2008/013736

申请日：2008-12-16

Applicant: MILLIPORE CORPORATION

Inventor： MOYA, Wilson ,  JABER, Jad

IPC: C07K1/30 ,  C07K1/32

CPC classification number: C07K1/32 ,  C07K1/30

Abstract: The present invention relates to a selectively soluble polymer capable of binding to a desired molecules in an unclarified mixture containing various biological materials and the methods of using such a polymer to purify a molecule from such a mixture. The polymer is soluble in the mixture under a certain set of process conditions such as pH or temperature and/or salt concentration and is rendered insoluble and precipitates out of solution upon a change in the process conditions. The polymer is capable of binding to the desired molecule (protein, polypeptide, etc) and remains capable of binding to that molecule even after the polymer is precipitated out of solution. The precipitate can then be filtered out from the remainder of the stream and the desired biomolecule is recovered such as by elution and further processed.

Abstract translation: 本发明涉及能够在含有各种生物材料的未澄清混合物中结合所需分子的选择性可溶性聚合物以及使用这种聚合物从这种混合物中纯化分子的方法。 聚合物在一定的工艺条件例如pH或温度和/或盐浓度下可溶于混合物中，并且在工艺条件改变时变得不溶解并沉淀出溶液。 聚合物能够结合到所需的分子（蛋白质，多肽等），并且即使在聚合物从溶液中沉淀出来之后仍然能够结合该分子。 然后可以从流的剩余部分中过滤出沉淀物，并回收所需的生物分子，例如通过洗脱和进一步处理。

公开(公告)号：WO2008065415A2

公开(公告)日：2008-06-05

申请号：PCT/GB2007004597

申请日：2007-11-30

Applicant: BIOLINE RES LTD ,  IGNATOV KONSTANTIN ,  KRAMAROV VLADIMIR ,  GUBANOV SERGEY IVANOVICH

Inventor： IGNATOV KONSTANTIN ,  KRAMAROV VLADIMIR ,  GUBANOV SERGEY IVANOVICH

IPC: C07K1/22 ,  C07K1/32 ,  C07K14/00 ,  C12N15/62 ,  G01N33/50

CPC classification number: C07K1/32 ,  C07K1/1075 ,  C07K1/1077 ,  C07K1/22 ,  C07K14/4728 ,  C07K2319/20 ,  C12N15/62

Abstract: The invention provides methods and materials for producing and purifying soluble targets, such as recombinant proteins, from a sample. The invention employs "tags" which can be appended to the target. By addition of a tag-binding entity (or "ligand", the terms are used interchangeably) to the tagged target, the solubility of the target can be reduced and it can be selectively precipitated. Preferred tags are metal binding peptide tags (which may share homology with Ca2+ binding EGF-like domains) wherein addition of appropriate sparingly soluble metal salts to the tagged target causes precipitation.

Abstract translation: 本发明提供从样品中产生和纯化可溶性靶标如重组蛋白质的方法和材料。 本发明使用可以附加到目标的“标签”。 通过向标记的靶添加标签结合实体（或“配体”，术语可互换使用），可以降低靶的溶解度并且可以选择性地沉淀。 优选的标签是金属结合肽标签（其可以与Ca2 +结合EGF样结构域共享同源性），其中向标记的靶标中加入适当的微溶性金属盐导致沉淀。

公开(公告)号：WO2006031644A3

公开(公告)日：2006-08-31

申请号：PCT/US2005032135

申请日：2005-09-09

Applicant: ADLYFE INC ,  ORSER CINDY S ,  PAN TAO

Inventor： ORSER CINDY S ,  PAN TAO

IPC: G01N33/483 ,  C07K1/32

CPC classification number: G01N33/6896 ,  G01N33/54393 ,  G01N2800/2828

Abstract: The present invention provides methods of making immobilized probes that are specific for prion proteins, methods of using such probes to bind, detect, and remove prion proteins from samples, and kits for practicing the invention. The invention discloses immobilized probes that are locked into a particular, pre-determined configuration and that retain their activity and specificity even when exposed to conditions that would typically alter their activity and specificity.

Abstract translation: 本发明提供了制备对朊病毒蛋白特异的固定化探针的方法，使用这种探针结合，检测和除去样品中的朊病毒蛋白的方法，以及用于实施本发明的试剂盒。 本发明公开了固定的探针，其被锁定到特定的预定构型并且即使在暴露于通常会改变其活性和特异性的条件下时仍保持其活性和特异性。

公开(公告)号：WO2005014622A3

公开(公告)日：2005-05-06

申请号：PCT/EP2004008609

申请日：2004-07-30

Applicant: HOFFMANN LA ROCHE ,  BERNTENIS NIKOLAOS ,  BUURMAN GERRIT ,  KROPSHOFER HARALD ,  MUELLER BERND CHRISTIAN ,  SPINDELDREHER SEBASTIAN THOMAS ,  VOGT ANNE ,  ZOLG WERNER

Inventor： BERNTENIS NIKOLAOS ,  BUURMAN GERRIT ,  KROPSHOFER HARALD ,  MUELLER BERND CHRISTIAN ,  SPINDELDREHER SEBASTIAN THOMAS ,  VOGT ANNE ,  ZOLG WERNER

IPC: C07K14/47 ,  C07K14/74 ,  C07K1/22 ,  A61K38/00 ,  A61K39/00 ,  C07K1/32 ,  G01N33/569

CPC classification number: C07K14/4713 ,  C07K14/70539

Abstract: The present invention provides novel naturally-processed MHC class II antigenic peptides; which originate from interferon-gamma-inducible lysosomal thiol reductase, integrin beta-2, phosphatitylinositol-4,5-bisphosphate 3-kinase, urokinase-type plasminogen activator, immunoglobulin heavy chain V-III region (VH26), DJ-1 protein, apolipoprotein B-100, 26S proteasome non-ATPase regulatory subunit 8, interleukin-1 receptor, fibromodulin, GM-CSF/IL-3/IL-5 receptor, sorting nexin 3, inter-alpha-trypsin inhibitor heavy chain H4, complement C4, complement C3 (alpha-chain), complement C3 (beta-chain), SH3 domain-binding glutamic acid-rich-like protein 3, interleukin-4-induced protein 1, hemopexin, Hsc70-interacting protein,invariant chain (Ii), retinoic acid receptor responder protein 2, fibronectin, cathepsin B, tripeptidyl-peptidase II, legumain, platelet activating factor receptor, poly- alpha-2.8-sialyltransferase, and ras-leated protein Rab-11B. Also provided are these antigenic peptides and the proteins they are derived from as markers for erosive and/or non-erosive RA. Moreover, these antigenic peptides linked to MHC class II molecules, antibodies reactive with said antigenic peptides, nucleic acids encoding said antigenic peptides, and nucleic acid constructs, host cells and methods for expressing said antigenic peptides are provided. The antigenic peptides of the invention can be used as markers in diagnosis of RA and in therapy as anti-RA vaccines.

Abstract translation: 本发明提供新型天然加工的MHC II类抗原肽; 来源于干扰素-γ诱导型溶酶体硫醇还原酶，整联蛋白β-2，磷脂酰肌醇-4,5-二磷酸3-激酶，尿激酶型纤溶酶原激活物，免疫球蛋白重链V-III区（VH26），DJ-1蛋白， 载脂蛋白B-100,26S蛋白酶体非ATPase调节亚单位8，白细胞介素-1受体，纤维调节蛋白，GM-CSF / IL-3 / IL-5受体，分选nexin 3，α间胰蛋白酶抑制剂重链H4，补体C4 ，补体C3（α链），补体C3（β链），SH3结构域结合谷氨酸样蛋白3，白细胞介素-4诱导的蛋白1，血红蛋白，Hsc70相互作用蛋白，不变链（Ii） ，视黄酸受体反应蛋白2，纤连蛋白，组织蛋白酶B，三肽基肽酶II，豆蔻酰胺，血小板活化因子受体，聚-α-2.8-唾液酸转移酶和ras-leated蛋白Rab-11B。 还提供了这些抗原肽和它们作为侵蚀性和/或非侵蚀性RA的标记物衍生的蛋白质。 此外，提供了与MHC II类分子连接的这些抗原肽，与所述抗原肽反应的抗体，编码所述抗原肽的核酸和核酸构建体，宿主细胞和用于表达所述抗原肽的方法。 本发明的抗原肽可用作RA诊断和抗RA疫苗治疗中的标志物。

公开(公告)号：WO2004026251A3

公开(公告)日：2004-09-02

申请号：PCT/US0329546

申请日：2003-09-22

Applicant: PHARMACIA CORP ,  BOYLE DENIS M ,  BUCKLEY JOHN J ,  JOHNSON GARY V ,  STEINMEYER DAVID E ,  TOAL MICHELE ,  AYKENT SERDAR ,  RATHORE ANURAG S

Inventor： BOYLE DENIS M ,  BUCKLEY JOHN J ,  JOHNSON GARY V ,  STEINMEYER DAVID E ,  TOAL MICHELE ,  AYKENT SERDAR ,  RATHORE ANURAG S

IPC: C07K1/18 ,  C07K14/61 ,  C07K1/22 ,  C07K1/32

CPC classification number: C07K14/61 ,  C07K1/18

Abstract: The present invention is directed generally to recombinant methods for making a desired pegylated protein and pooling of same. These method(s) yield a polypeptide product containing reduced levels of aggregate thereof pooled to provide the desired pegylated isoforms thereof.

Abstract translation: 本发明一般涉及制备所需的聚乙二醇化蛋白质和合并其的重组方法。 这些方法产生含有降低水平的聚集体的多肽产物，其汇集以提供其所需的聚乙二醇化的同种型。

公开(公告)号：WO99033862A1

公开(公告)日：1999-07-08

申请号：PCT/US1998/026251

申请日：1998-12-10

IPC: C12N15/09 ,  B01D11/04 ,  B01D15/02 ,  B01D15/08 ,  B01D61/02 ,  B01D61/14 ,  C07K1/16 ,  C07K1/20 ,  C07K1/22 ,  C07K1/32 ,  C12N7/02 ,  G01N30/02 ,  G01N30/06 ,  G01N30/88

CPC classification number: C07K1/34 ,  C07K1/16 ,  C07K1/20 ,  C07K1/22 ,  C07K1/32 ,  C07K1/36 ,  G01N30/02 ,  G01N30/06 ,  G01N2030/8813 ,  G01N2030/8827 ,  G01N2030/8831 ,  Y10S436/828 ,  B01D15/34

Abstract: The present invention is directed to novel methods for enhancing the ability to separate a species of interest from other different species present in a free solution mixture thereof which takes advantage of interactions that occur between soluble, small molecular weight ligands and the species of interest. The small molecular weight ligands employed in the present invention function to interact with a species of interest in a mixture of different species through either affinity, hydrophobic and/or ionic interactions, thereby altering the molecular weight, hydrodynamic volume and/or isoelectric point of the species of interest and rendering it separable from other component(s) in the mixture.

Abstract translation: 本发明涉及增强从存在于其游离溶液混合物中的其它不同物种分离感兴趣物种的能力的新方法，其利用可溶性，小分子量配体和感兴趣物种之间发生的相互作用。 本发明中使用的小分子量配体通过亲和力，疏水和/或离子相互作用在不同物种的混合物中与感兴趣的物种相互作用，由此改变了分子量，流体动力学体积和/或等电点 感兴趣的物种，使其与混合物中的其他成分分离。