You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 28, 2024

Claims for Patent: 8,703,498


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 8,703,498
Title:Multi-dimensional chromatographic methods for separating N-glycans
Abstract: A multi-dimensional chromatographic method for the separation of N-glycans. The method comprises providing a glycan preparation that includes at least one negatively charged N-glycan. The glycan preparation is then separated by anion-exchange chromatography and at least one secondary chromatographic technique.
Inventor(s): Parsons; Ian Christopher (Belmont, MA), Zheng; Ting (Sunnyvale, CA), Gunay; Nur Sibel (Chestnut Hill, MA), Bosques; Carlos J. (Arlington, MA)
Assignee: Momenta Pharmaceuticals, Inc. (Cambridge, MA)
Application Number:13/630,594
Patent Claims:1. A method of characterizing a mixture of N-glycans, said method comprising steps of: (i) providing a glycan preparation, wherein the glycan preparation includes at least one charged N-glycan and a known quantity of a reference N-glycan, wherein the reference N-glycan is labeled with a labeling agent; (ii) separating the glycan preparation by anion-exchange chromatography to generate a plurality of sample fractions; (iii) separating a first portion of the plurality of sample fractions by at least one secondary chromatographic technique to obtain first separated fractions; (iv) separating a second portion of the plurality of sample fractions by at least one secondary chromatographic technique that differs from the secondary chromatographic technique from (iii) to obtain second separated fractions; (v) quantifying at least one N-glycan relative to the reference N-glycan in at least a portion of the first separated fractions, or in at least a portion of the second separated fractions, or both; and (vi) recording the result from (v) in a quality control record.

2. The method of claim 1, wherein the at least one secondary chromatographic technique from (iii) is selected from the group consisting of reversed phase liquid chromatography (RP), normal phase liquid chromatography (NP), ion-pairing reverse phase chromatography (IP-RP), size exclusion chromatography, affinity chromatography (AC), capillary electrophoresis (CE); fluorophore-assisted carbohydrate electrophoresis (FACE); electrochromatography, and micellar electrokinetic chromatography (MEKC).

3. The method of claim 1, wherein the at least one secondary chromatographic technique from (iii) is a reversed phase chromatographic technique.

4. The method of claim 3, wherein the reversed-phase chromatographic technique employs a C18 reverse phase resin.

5. The method of claim 3, wherein the reversed-phase chromatographic technique employs a porous graphitized-carbon (PGC) resin.

6. The method of claim 1, wherein the at least one secondary chromatographic technique from (iii) is a normal phase chromatographic technique.

7. The method of claim 6, wherein the normal phase chromatographic technique employs a modified silica gel.

8. The method of claim 7, wherein the modified silica gel is selected from the group consisting of cyano-modified silica, amine-modified silica, and amide-modified silica.

9. The method of claim 1, wherein the at least one secondary chromatographic technique from (iv) is selected from the group consisting of reversed phase liquid chromatography (RP), normal phase liquid chromatography (NP), ion-pairing reverse phase chromatography (IP-RP), size exclusion chromatography, affinity chromatography (AC), capillary electrophoresis (CE); fluorophore-assisted carbohydrate electrophoresis (FACE); electrochromatography, and micellar electrokinetic chromatography (MEKC).

10. The method of claim 1, wherein the at least one secondary chromatographic technique from (iv) is a reversed phase chromatographic technique.

11. The method of claim 10, wherein the reversed-phase chromatographic technique employs a resin selected from the group consisting of a C18 reverse phase resin and a porous graphitized-carbon (PGC) resin.

12. The method of claim 1, wherein the at least one secondary chromatographic technique from (iv) is a normal phase chromatographic technique.

13. The method of claim 12, wherein the normal phase chromatographic technique employs a modified silica gel.

14. The method of claim 13, wherein the modified silica gel is selected from the group consisting of cyano-modified silica, amine-modified silica, and amide-modified silica.

15. The method of claim 1, wherein the at least one secondary chromatographic technique from (iii) is a normal phase chromatographic technique and the at least one secondary chromatographic technique from (iv) is a reverse phase chromatographic technique.

16. The method of claim 1, wherein the first portion of the plurality of sample fractions comprises the first half to two-thirds of the fractions from the anion exchange chromatography.

17. The method of claim 1, wherein the second portion of the plurality of sample fractions comprises the second half to one-third of the fractions from the anion exchange chromatography.

18. A method of characterizing a mixture of N-glycans, the method comprising steps of: (i) providing a glycan preparation, wherein the glycan preparation includes at least one charged N-glycan and a known quantity of a reference N-glycan, wherein the reference N-glycan is labeled with a labeling agent; (ii) separating the glycan preparation by anion-exchange chromatography to generate a plurality of sample fractions; (iii) separating a first portion of the plurality of sample fractions by at least one secondary chromatographic technique to obtain first separated fractions; (iv) separating a second portion of the plurality of sample fractions by at least one secondary chromatographic technique that differs from the secondary chromatographic technique from (iii) to obtain second separated fractions; (v) quantifying at least one N-glycan relative to the reference N-glycan in at least a portion of the first separated fractions, or in at least a portion of the second separated fractions, or both; and (vi) comparing the result from (v) with that of a reference sample.

19. The method of claim 18, further comprising a step of comparing the result from (v) with that of a historical record of the reference sample.

20. A method of characterizing a mixture of N-glycans, the method comprising steps of: (i) providing a glycan preparation from a therapeutic glycoprotein preparation, wherein the glycan preparation includes at least one charged N-glycan and a known quantity of a reference N-glycan, wherein the reference N-glycan is labeled with a labeling agent; (ii) separating the glycan preparation by anion-exchange chromatography to generate a plurality of sample fractions; (iii) separating a first portion of the plurality of sample fractions by at least one secondary chromatographic technique to obtain first separated fractions; (iv) separating a second portion of the plurality of sample fractions by at least one secondary chromatographic technique that differs from the secondary chromatographic technique from (iii) to obtain second separated fractions; and (v) quantifying at least one N-glycan relative to the reference N-glycan in at least a portion of the first separated fractions, or in at least a portion of the second separated fractions, or both.

21. The method of claim 20, wherein the therapeutic glycoprotein preparation is obtained from a culture of cells producing a therapeutic glycoprotein.

22. The method of claim 21, further comprising a step of comparing the result from (v) with that of a reference sample.

23. The method of claim 22, wherein the reference sample is a glycan preparation from a different batch of cells producing the therapeutic glycoprotein.

24. The method of claim 22, wherein the reference sample is a glycan preparation from the culture of cells at a different time than the therapeutic glycoprotein preparation.

25. The method of claim 22, further comprising a step of recording the result of the comparing in a quality control record for the therapeutic glycoprotein preparation.

26. The method of claim 22, wherein the result from (v) is compared with a historical record of the reference sample.

27. The method of claim 20, wherein the therapeutic glycoprotein preparation is an antibody preparation.

28. The method of claim 27, wherein the antibody preparation is a preparation of alemtuzumab, etanercept, adalimumab, abatacept, infliximab, bevacizumab, rituximab, natalizumab, or cetuximab.

Details for Patent 8,703,498

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Genentech, Inc. RITUXAN rituximab Injection 103705 11/26/1997 ⤷  Try a Trial 2027-04-16
Idec Pharmaceuticals Corp. RITUXAN rituximab Injection 103737 02/19/2002 ⤷  Try a Trial 2027-04-16
Janssen Biotech, Inc. REMICADE infliximab For Injection 103772 08/24/1998 ⤷  Try a Trial 2027-04-16
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.