Systems and methods for using behavior data of impurities and target proteins to design downstream processes

Patent metadata

Field	Value
Publication number	US-2020251186-A1
Application number	US-201816499776-A
Country	US
Kind code	A1
Filing date	Mar 30, 2018
Priority date	Apr 1, 2017
Publication date	Aug 6, 2020
Grant date	—

Abstract

Systems and methods for generating and evaluating candidate sequences of partitioning steps to partition at least one biologically produced product from at least one impurity. In some embodiments, a plurality of candidate sequences of partitioning steps may be generated, wherein at least one candidate sequence of the plurality of candidate sequences comprises a plurality of partitioning steps in a specified order. The plurality of candidate sequences may be evaluated. For instance, a data set associated with the at least one partitioning step may be accessed, the data set comprising: first data indicative of a behavior of the at least one biologically produced product with respect to the at least one partitioning step; and second data indicative of a behavior of the at least one impurity with respect to the at least one partitioning step. The at least one candidate sequence may be scored based at least in part on the data set.

First claim

What is claimed is:

1 . A method for generating and evaluating candidate sequences of partitioning steps to partition at least one biologically produced product from at least one impurity, the method comprising acts of:
generating a plurality of candidate sequences of partitioning steps, wherein at least one candidate sequence of the plurality of candidate sequences comprises a plurality of partitioning steps in a specified order; and evaluating the plurality of candidate sequences, comprising, for at least one partitioning step in the at least one candidate sequence:
accessing a data set associated with the at least one partitioning step, the data set comprising:
first data indicative of a behavior of the at least one biologically produced product with respect to the at least one partitioning step; and
second data indicative of a behavior of the at least one impurity with respect to the at least one partitioning step; and

scoring the at least one candidate sequence based at least in part on the data set.

2 . The method of claim 1 , wherein evaluating the plurality of candidate sequences comprises:
assigning a score to each of the candidate sequences; and ranking the candidate sequences based on the scores.

3 . The method of claim 1 , wherein the at least one candidate sequence is scored based on a degree to which the plurality of partitioning steps, when performed in the specified order, complement each other in partitioning the at least one biologically produced product from the at least one impurity.

4 . The method of claim 1 , wherein the data set associated with the at least one partitioning step is obtained using at least one analytical technique selected from a group consisting of: liquid chromatography-mass spectrometry (LC-MS), matrix-assisted laser absorption/ionization (MALDI), ultraviolet (UV) absorbance analysis, fluorescence detection, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and isoelectric focusing (IEF).

5 . The method of claim 1 , wherein:
the at least one candidate sequence comprises at least first and second partitioning steps, the first partitioning step comprising applying a first partitioning technique and the second partitioning step comprising applying a second partitioning technique; and the first and second partitioning techniques are different.

6 . The method of claim 1 , wherein:
the at least one candidate sequence comprises at least first and second partitioning steps, the first and second partitioning steps comprising applying a same partitioning technique.

7 . The method of claim 6 , wherein:
the first partitioning step comprises applying the partitioning technique with a first set of one or more parameters; and the second partitioning step comprises applying the partitioning technique with a second set of one or more parameters different from the first set of one or more parameters.

8 . The method of claim 7 , wherein the first and second sets of one or more parameters differ in one or more materials.

9 . The method of claim 7 , wherein the first and second sets of one or more parameters differ in one or more conditions.

10 . The method of claim 1 , wherein the at least one impurity results from one or more processes used to produce the at least one biologically produced product.

11 . The method of claim 1 , wherein the at least one impurity comprises a variant or an aggregate of at least one biologically produced product.

12 . The method of claim 1 , wherein the at least one biologically produced product comprises at least one protein product.

13 . The method of claim 1 , wherein the at least one biologically produced product comprises at least one pharmaceutical product.

14 . A method for generating and evaluating candidate sequences of chromatography steps to partition at least one pharmaceutical product from at least one impurity, the at least one pharmaceutical product being biologically produced, the method comprising acts of:
generating a plurality of candidate sequences of chromatography steps, wherein at least one candidate sequence of the plurality of candidate sequences comprises a plurality of chromatography steps in a specified order; and evaluating the plurality of candidate sequences, comprising, for at least one chromatography step in the at least one candidate sequence:
accessing a data set associated with the at least one chromatography step, the data set comprising:
first data indicative of a behavior of the at least one pharmaceutical product with respect to the at least one chromatography step; and
second data indicative of a behavior of the at least one impurity with respect to the at least one chromatography step; and

scoring the at least one candidate sequence based at least in part on the data set.

15 . The method of claim 14 , wherein evaluating the plurality of candidate sequences comprises:
assigning a score to each of the candidate sequences; and ranking the candidate sequences based on the scores.

16 - 17 . (canceled)

18 . The method of claim 14 , wherein the at least one candidate sequence is scored based on a degree to which the plurality of chromatography steps, when performed in the specified order, are orthogonal to each other in partitioning the at least one pharmaceutical product from the at least one impurity.

19 . The method of claim 14 , wherein the at least one candidate sequence is scored based on a degree to which the plurality of chromatography steps, when performed in the specified order, complement each other in partitioning the at least one pharmaceutical product from the at least one impurity.

20 . The method of claim 14 , further comprising:
using the first data indicative of the behavior of the at least one pharmaceutical product with respect to the at least one chromatography step to classify the at least one chromatography step as a bind-elute step, a flow-through step, or a weak partitioning step.

21 . The method of claim 14 , wherein:
the at least one chromatography step comprises collecting a plurality of fractions, each fraction of the plurality of fractions corresponding to a respective time interval of a plurality of time intervals; and the method further comprises an act of using the first data indicative of the behavior of the at least one pharmaceutical product with respect to the at least one chromatography step to identify at least one fraction of the plurality of fractions as an elution fraction for the at least one pharmaceutical product.

22 - 62 . (canceled)

63 . A method for generating and evaluating candidate sequences of chromatography steps to partition at least one pharmaceutical product from at least one process-related impurity and/or at least one product-related impurity, the at least one pharmaceutical product being biologically produced, the method comprising acts of:
generating a plurality of candidate sequences of chromatography steps, wherein at least one candidate sequence of the plurality of candidate sequences comprises a plurality of chromatography steps in a specified order; evaluating the plurality of candidate sequences, comprising, for at least one chromatography step in the at least one candidate sequence:
accessing a data set comprising first data indicative of a behavior of the at least one process-related impurity with respect to the at least one chromatography step;
accessing a data set comprising second data indicative of a behavior of the at le

Assignees

• Massachusetts Inst Technology
• Rensselaer Polytech Inst

Inventors

• Love J Christopher
• Love Kerry R
• Cramer Steven
• Timmick Steven
• Vecchiarello Nicholas
• Goodwine Chaz
• Crowell Laura
• Stockdale Alan
• Braatz Richard Dean
• Lu Amos Enshen

Classifications

• G16B40/00

  ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding · CPC title

• G01N30/8658

  Optimising operation parameters · CPC title

• G16C20/20

  Identification of molecular entities, parts thereof or of chemical compositions · CPC title

• C07K16/00

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C07K2317/569

  Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® · CPC title