Systems and methods for assessing therapeutic proteins

Patent metadata

Field	Value
Publication number	US-2017276659-A1
Application number	US-201515508551-A
Country	US
Kind code	A1
Filing date	Sep 4, 2015
Priority date	Sep 5, 2014
Publication date	Sep 28, 2017
Grant date	—

Abstract

Systems and methods for assessing the oxidation status of a pharmaceutical preparations are provided herein. Methods provided herein are particularly useful for assessing pharmaceutical preparations comprising therapeutic proteins (e.g., therapeutic antibodies).

First claim

What is claimed is:

1 . A method of assessing a pharmaceutical preparation, the method comprising:
determining a redox potential of the pharmaceutical preparation; and determining the oxidation status of the pharmaceutical preparation based on the redox potential of the pharmaceutical preparation.

2 . The method of claim 1 , wherein the step of determining the redox potential of the pharmaceutical preparation comprises determining a potential of a redox couple corrected by a formulation buffer of the pharmaceutical preparation, and wherein the oxidation status of the pharmaceutical preparation is determined based on a change in potential of the redox couple due to its interaction with the pharmaceutical preparation.

3 . The method of claim 1 further comprising
(i) determining a potential between an indicator electrode and a reference electrode disposed in a solution that comprises a redox couple, thereby determining the redox potential;
(ii) determining a change in potential between the indicator electrode and the reference electrode resulting from presence of the pharmaceutical preparation in the solution that comprises the redox couple; and
(iii) determining the oxidation status of the pharmaceutical preparation based on the change in potential.

4 . The method of claim 1 further comprising
(i) determining a potential between an indicator electrode and a reference electrode disposed in a solution that comprises a redox couple, thereby determining the redox potential;
(ii) determining a potential between an indicator electrode and a reference electrode resulting from presence of the formulation buffer in a solution that comprises a redox couple, thereby correcting the redox potential;
(iii) determining a change in potential between the indicator electrode and the reference electrode resulting from presence of the pharmaceutical preparation in the solution that comprises the redox couple and formulation buffer; and
(iv) determining the oxidation status of the pharmaceutical preparation based on the change in potential.

5 . The method of claim 4 , wherein step (iv) comprises evaluating a reference standard that relates a change in potential to an oxidation status of the pharmaceutical preparation.

6 . The method of claim 5 , wherein the reference standard relates the change in potential to a mass spectroscopically determined oxidation status of the pharmaceutical preparation.

7 . The method of claim 1 , wherein the indicator electrode is a platinum, gold, palladium, rhodium, or carbon electrode.

8 . The method of claim 7 , wherein the reference electrode is a silver/silver chloride reference electrode.

9 . The method of any one of claims 1 to 8 , wherein the redox couple comprises Hexamamineruthenium(II)chloride and Hexamamineruthenium(III)chloride.

10 . The method of claim 9 , wherein the concentration of Hexamamineruthenium(II)chloride is between 10 −2 M and 10 −4 M.

11 . The method of claim 9 or 10 , wherein the concentration of Hexamamineruthenium(III)chloride is between 10 −2 M and 10 −4 M.

12 . The method in any one of claims 9 to 11 , wherein the concentration of Hexamamineruthenium(II)chloride is 10 −2 M and the concentration of Hexamamineruthenium(III)chloride is 10 −4 M.

13 . The method of any one of claims 1 to 12 , wherein the pharmaceutical preparation comprises a protein, a nucleic acid, or a small molecule.

14 . The method of any one of claims 1 to 13 , wherein the pharmaceutical preparation comprises a protein.

15 . The method of claim 14 , wherein the protein is an immunoglobulin or fragment thereof.

16 . The method in any of claims 1 to 15 , wherein the pharmaceutical preparation comprises STX-100, natalizumab, BIIB037, Anti-TWEAK, Anti-BDCA2, Daclizumab.

17 . The method in any one of claims 1 to 16 , wherein the pharmaceutical preparation comprises an excipient.

18 . The method of claim 17 , wherein the excipient comprises a polysorbate or an amino acid.

19 . The method of claim 18 , wherein the polysorbate is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, and polysorbate 80.

20 . The method of claim 18 , wherein the amino acid comprises arginine, glycine or histidine.

21 . The method of any one of claims 1 to 20 , wherein the change in potential measured in step (ii) is adjusted based on an extent of change in potential between the indicator electrode and the reference electrode that results from a buffer component of the pharmaceutical preparation.

22 . The method of claim 21 , wherein the buffer component comprises sodium sulfate, sodium citrate, sodium phosphate, succinate, sodium chloride, potassium nitrate, or sucrose.

23 . The method of any one of claims 1 to 21 further comprising, prior to step (i), removing a component of the pharmaceutical preparation that affects the potential of the redox couple.

24 . The method of claim 23 , wherein the component is an arginine or a polysorbate.

25 . The method of any one of claims 1 to 24 , wherein the oxidation status is indicative of activity of the pharmaceutical preparation.

26 . The method of 25 further comprising evaluating activity of the pharmaceutical preparation using a bioassay.

27 . The method in any one of claims 25 to 26 , wherein the bioassay comprises evaluating efficacy or toxicity of the pharmaceutical preparation.

28 . The method in any one of claims 1 to 27 , wherein the oxidation status of the pharmaceutical preparation is determined on two or more occasions.

29 . The method of 28 , further comprising determining a change in activity of the pharmaceutical preparation based on the oxidation status of the pharmaceutical preparation is determined on the two or more occasions.

30 . A method of assessing a pharmaceutical preparation, the method comprising:
potentiometrically determining the oxidation status of the pharmaceutical preparation.

31 . A method of assessing activity of a biomolecule, the method comprising
determining a redox potential between an indicator electrode and a reference electrode disposed in a solution comprising the biomolecule; and determining activity of the biomolecule based on the redox potential.

32 . A method of assessing the activity of a biomolecule, the method comprising
(i) determining a potential between an indicator electrode and an reference electrode disposed in a solution that comprises a redox couple; (ii) determining a change in potential between the indicator electrode and the reference electrode resulting from presence of the biomolecule in the solution that comprises the redox couple; and (iii) determining the activity of the biomolecule based on the change in potential.

33 . The method of claim 32 , wherein step (iii) comprises evaluating a reference standard that relates a change in potential to the activity of the biomolecule.

34 . The method in any one of claims 1 to 33 , wherein the biomolecule is a protein, nucleic acid, or small molecule.

35 . The method of claim 34 , wherein the protein is an immunoglobulin or fragment thereof.

36 . The method in any one of claims 1 to 35 , wherein the indicator electrode

Assignees

• Biogen Ma Inc

Inventors

• Turyan Iva
• Khatwani Nikhil
• Sosic Zoran

Classifications

• G01N27/4161

  measuring the voltage and using a constant current supply, e.g. chronopotentiometry · CPC title

• G01N33/15 Primary

  Medicinal preparations {; Physical properties thereof, e.g. dissolubility} · CPC title

• G01N27/4168 Primary

  Oxidation-reduction potential, e.g. for chlorination of water (water analysis G01N33/18) · CPC title