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    Method for preparing aqueous solutions of a defined pH
    1.
    发明授权
    Method for preparing aqueous solutions of a defined pH 有权

    公开(公告)号：US11911712B2

    公开(公告)日：2024-02-27

    申请号：US16652204

    申请日：2018-09-21

    申请人： Fujifilm Diosynth Biotechnologies UK Limited

    发明人： Tibor Nagy

    IPC分类号： B01D15/16 ,  G01N30/34 ,  G05D21/02 ,  B01F25/42 ,  B01F35/221 ,  B01F35/71

    CPC分类号： B01D15/168 ,  B01F25/42 ,  B01F35/2211 ,  B01F35/7176 ,  G01N30/34 ,  G05D21/02

    摘要： A method for preparing an aqueous solution of a defined pH comprising an acid, a base and optionally one or more additives is provided. The method comprises the steps of:
    a) calculating the theoretical concentrations of acid and base for the solution to have the defined pH using the Henderson-Hasselbach equation in combination with the Debye Huckel theory for a range of different additive concentrations; b) preparing a sample of the buffer for the range of additive concentrations and measuring the actual pH for each additive concentration; c) calculating a value for delta pH, ΔpH, being the difference between the theoretical pH and the actual pH, for each additive concentration; d) generating a mathematical model describing the relationship of ΔpH with additive concentration; e) selecting the defined pH and additive concentrations; f) using the mathematical model generated in step d) to calculate ΔpH for the defined pH and additive concentration; g) calculating a ΔpH-corrected pH by summing the defined pH and delta pH; h) using the ΔpH-corrected pH to calculate the concentrations of acid and base using the Henderson-Hasselbach equation in combination with the Debye Huckel theory; i) preparing the solution using the concentrations calculated in step h).

    IN VITRO PREDICTION OF IN VIVO HALF-LIFE
    2.
    发明申请
    IN VITRO PREDICTION OF IN VIVO HALF-LIFE 审中-公开

    公开(公告)号：US20170227547A1

    公开(公告)日：2017-08-10

    申请号：US15271091

    申请日：2016-09-20

    申请人： Hoffmann-La Roche Inc.

    发明人： Thomas Emrich ,  Hubert Kettenberger ,  Tilman Schlothauer ,  Angela Schoch

    IPC分类号： G01N33/68 ,  B01D15/38 ,  B01D15/16

    CPC分类号： G01N33/6854 ,  B01D15/168 ,  B01D15/3809 ,  C07K16/00 ,  C07K2317/52 ,  C07K2317/94

    摘要： Herein is reported a method for determining the presence of antibody-Fab-FcRn interaction in an antibody-Fc-FcRn complex influencing the in vivo half-life comprising the steps of a) determining the retention time of the antibody on an FcRn affinity chromatography column with a positive linear pH gradient elution in the presence of a first sodium chloride concentration, and b) determining the retention time of the antibody on an FcRn affinity chromatography column with a positive linear pH gradient elution in the presence of a second sodium chloride concentration, whereby the presence of antibody-Fab-FcRn interaction in an antibody-Fc-FcRn complex influencing the in vivo half-life is determined if the retention time determined in step a) and the retention time determined in step b) are substantially different.

    AFFINITY CHROMATOGRAPHY MATRIX
    4.
    发明申请
    AFFINITY CHROMATOGRAPHY MATRIX 有权
    亲属色谱矩阵

    公开(公告)号：US20130338339A1

    公开(公告)日：2013-12-19

    申请号：US13995977

    申请日：2011-12-19

    申请人： Tomas Bjorkman ,  Bjorn Noren ,  Gustav Rodrigo ,  Jelena Vasic ,  Per-Mikael Aberg

    发明人： Tomas Bjorkman ,  Bjorn Noren ,  Gustav Rodrigo ,  Jelena Vasic ,  Per-Mikael Aberg

    IPC分类号： C07K16/12

    CPC分类号： C07K16/1271 ,  B01D15/168 ,  B01D15/3809 ,  B01J20/286 ,  B01J20/289 ,  B01J20/3212 ,  B01J20/3219 ,  B01J20/3274 ,  C07K1/22 ,  C07K14/31

    摘要： The present invention relates to a method of separating one or more immunoglobulin containing proteins from a liquid. The method includes first contacting the liquid with a separation matrix comprising ligands immobilised to a support; allowing the immunoglobulin containing proteins to adsorb to the matrix by interaction with the ligands; followed by an optional step of washing the matrix containing the immunoglobulin containing proteins adsorbed thereon; and recovering said immunoglobulin containing proteins by contacting the matrix with an eluent which releases the proteins. The method improves upon previous separation methods in that each of the ligands comprises one or more of a protein A domain (E, D, A, B, C), or protein Z, or a functional variant thereof, with at least one of the monomers having a substitution of the Asparagine or Histidine at the position corresponding to H18 of B domain of Protein A or Protein Z, and wherein the ligand provides an increase in elution pH compared to non-substituted ligand.

    摘要翻译： 本发明涉及从液体中分离一种或多种含免疫球蛋白的蛋白质的方法。 该方法包括首先使液体与包含固定在载体上的配体的分离基质接触; 允许含有免疫球蛋白的蛋白质通过与配体的相互作用吸附到基质上; 随后是洗涤含有其上吸附有蛋白质的蛋白质的基质的任选步骤; 并通过使基质与释放蛋白质的洗脱液接触来回收所述含有免疫球蛋白的蛋白质。 该方法改进了以前的分离方法，因为每种配体包含蛋白A结构域（E，D，A，B，C）或蛋白质Z或其功能变体中的一种或多种，​​其中至少一种 在相应于蛋白A或蛋白Z的B结构域的H18的位置处取代天门冬酰胺或组氨酸的单体，其中与未取代的配体相比，配体提供了洗脱pH的增加。

    External gradient chromatofocusing
    5.
    发明授权
    External gradient chromatofocusing 失效
    外部梯度色谱聚焦

    公开(公告)号：US07790025B2

    公开(公告)日：2010-09-07

    申请号：US10556562

    申请日：2004-05-14

    申请人： Latchezar I. Tsonev ,  Allen G. Hirsh

    发明人： Latchezar I. Tsonev ,  Allen G. Hirsh

    IPC分类号： B01D15/08

    CPC分类号： B01D15/168 ,  B01D15/362 ,  B01D15/363 ,  B01D15/426 ,  C07K1/16 ,  C07K1/18 ,  C07K1/26 ,  C07K1/28 ,  G01N30/02

    摘要： The invention provides novel methods for the separation of charged molecules such as proteins according to the isoelectric points (pI's) and includes the systems and buffering compositions employed for isolating charged molecules. The invention further provides for modifications to the above described chromatographic methods that enable the separation of charged molecules exhibiting virtually identical pI's by shifting both the buffer's pKa and the pI's of the eluted charged molecules while they are traversing the ion exchange column.

    摘要翻译： 本发明提供了用于根据等电点（pI）分离带电分子如蛋白质的新方法，并且包括用于分离带电分子的系统和缓冲组合物。 本发明进一步提供对上述色谱方法的修改，其能够通过在洗脱的带电荷分子横过离子交换柱的同时移动缓冲液的pKa和洗脱的带电分子的pI来分离表现出实质上相同的pI的带电分子。

    RECYCLING OF ENZYMES FROM BIOREACTORS
    9.
    发明申请
    RECYCLING OF ENZYMES FROM BIOREACTORS 审中-公开
    生物反应器回收酶

    公开(公告)号：US20150307902A1

    公开(公告)日：2015-10-29

    申请号：US13806052

    申请日：2011-06-24

    申请人： Allan Otto Fog LIHME

    发明人： Allan Otto Fog LIHME

    IPC分类号： C12P7/10 ,  C12P7/16 ,  C12P7/64 ,  C12P7/04

    CPC分类号： C12P7/10 ,  B01D15/168 ,  B01D15/1892 ,  B01D15/3809 ,  C07K1/22 ,  C12P7/04 ,  C12P7/16 ,  C12P7/649 ,  C12P19/02 ,  C12P19/14 ,  Y02E50/16 ,  Y02E50/17

    摘要： A method of conducting an enzymatic process in which the enzymes are recovered and reused in at least a second iteration of the process, wherein each iteration of the process comprises the steps of: (a) providing a heterogeneous substrate solution, in which the substrate is fully soluble, partially soluble or insoluble; (b) adding an enzyme or mixture of enzymes to the heterogeneous substrate solution; and (c) allowing an enzymatic reaction of the substrate to proceed; wherein, after completion of step (c) for each iteration, the enzyme is recovered from the mixture resulting from step (c) according to the following steps: (d) conducting a non-packed-bed adsorption process comprising contacting the reaction mixture with an adsorbent that adsorbs the enzyme in order to separate the enzyme from the reaction mixture resulting from step (c); (e) optionally washing unbound material from the adsorbent; and (f) desorbing the enzyme from the adsorbent; and further wherein the desorbed enzyme obtained in step (f) is used in step (b) of at least one subsequent iteration of the process.

    摘要翻译： 一种进行酶过程的方法，其中酶在该方法的至少第二次迭代中回收和重复使用，其中该方法的每次迭代包括以下步骤：（a）提供非均相底物溶液，其中所述底物为 完全溶解，部分溶解或不溶; （b）向所述非均相底物溶液中加入酶或酶的混合物; 和（c）允许底物的酶促反应进行; 其中，对于每次迭代，在步骤（c）完成后，根据以下步骤从步骤（c）得到的混合物中回收酶：（d）进行非填充床吸附方法，包括使反应混合物与 吸附酶以便将酶与步骤（c）得到的反应混合物分离的吸附剂; （e）任选地从吸附剂洗涤未结合的材料; 和（f）从吸附剂中解吸酶; 并且其中步骤（f）中获得的解吸酶在步骤（b）中用于该方法的至少一次后续迭代。