Claims for Patent: 9,182,467
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Summary for Patent: 9,182,467
Title: | Comparative analysis of protein conformations by using 2D NOESY NMR spectra |
Abstract: | The present disclosure provides a method for determining the relative conformations of a protein provided in different protein preparations, comprising steps of: (i) obtaining a first 2D NOESY NMR spectrum of a first protein preparation; (ii) obtaining a second 2D NOESY NMR spectrum of a second protein preparation; and (iii); determining whether a protein has a different conformation in the first and second protein preparations by comparing one or more cross-peaks in the first 2D NOESY NMR spectrum with one or more corresponding cross-peaks in the second 2D NOESY NMR spectrum. |
Inventor(s): | Parsons; Ian Christopher (Belmont, MA), Lansing; Jonathan (Reading, MA), Bosques; Carlos J. (Arlington, MA), Beccati; Daniela (Boston, MA) |
Assignee: | Momenta Pharmaceuticals, Inc. (Cambridge, MA) |
Application Number: | 12/595,867 |
Patent Claims: | 1. A method of measuring differences in relative conformations of a recombinant glycoprotein provided in different preparations, comprising steps of: generating a first 2D NOESY NMR
spectrum of a first preparation of a recombinant glycoprotein using an NMR spectrometer, wherein the recombinant glycoprotein has been recombinantly expressed in a mammalian cell; generating a second 2D NOESY NMR spectrum, comparable to the first
spectrum, of a second preparation of the same recombinant glycoprotein using an NMR spectrometer, wherein the recombinant gycoprotein has been recombinantly expressed in a mammalian cell; and measuring differences in conformation of the recombinant
glycoprotein in the first and second glycoprotein preparations by comparing one or more cross-peaks in the first 2D NOESY NMR spectrum with one or more corresponding cross-peaks in the second 2D NOESY NMR spectrum.
2. The method of claim 1, wherein the step of measuring comprises: comparing chemical shifts of one or more cross-peaks in the first 2D NOESY NMR spectrum with chemical shifts of one or more corresponding cross-peaks in the second 2D NOESY NMR spectrum. 3. The method of claim 1, wherein the step of measuring comprises: comparing intensities of one or more cross-peaks in the first 2D NOESY NMR spectrum with intensities of one or more corresponding cross-peaks in the second 2D NOESY NMR spectrum. 4. The method of claim 1, wherein the second glycoprotein preparation is a therapeutic glycoprotein product. 5. The method of claim 1, wherein the first and second glycoprotein preparations were prepared by the same method. 6. The method of claim 1, wherein the first and second glycoprotein preparations were prepared by different methods. 7. The method of claim 1, wherein the one or more cross-peaks are the result of correlations between amide NH nuclei. 8. The method of claim 1, wherein the one or more cross-peaks are the result of correlations between amide NH nuclei and CH.sub.3 methyl nuclei. 9. The method of claim 1, wherein the one or more cross-peaks are the result of correlations between CH.sub.3 methyl nuclei. 10. The method of claim 1, wherein the one or more cross-peaks are the result of correlations between amide NH nuclei and indole NH nuclei. 11. The method of claim 1, wherein the one or more cross-peaks are the result of correlations between CH.sub.3 methyl nuclei and indole NH nuclei. 12. The method of claim 1, wherein the one or more cross-peaks are the result of correlations between amide NH nuclei and H-.alpha. nuclei. 13. The method of claim 1, wherein the one or more cross-peaks are the result of correlations between amide NH nuclei and glycosidic nuclei. 14. The method of claim 1 further comprising a step of: assigning the one or more cross-peaks. 15. A method of producing a recombinant glycoprotein, comprising steps of: providing a first preparation of a recombinant glycoprotein from a mammalian cell culture expressing the recombinant glycoprotein; providing a second preparation of the same recombinant glycoprotein from a mammalian cell culture expressing the recombinant glycoprotein; obtaining a first 2D NOESY NMR spectrum of the first preparation; obtaining a second 2D NOESY NMR spectrum, comparable to the first spectrum, of the second preparation; determining relative conformations of the recombinant glycoprotein in the first and second glycoprotein preparations by comparing one or more cross-peaks in the first 2D NOESY NMR spectrum with one or more corresponding cross-peaks in the second 2D NOESY NMR spectrum; and producing the recombinant glycoprotein in the mammalian cell culture if the relative conformations of the recombinant glycoprotein in the first and second glycoprotein preparations are at least 75% similar. 16. The method of claim 15, wherein the step of determining comprises: comparing chemical shifts of one or more cross-peaks in the first 2D NOESY NMR spectrum with chemical shifts of one or more corresponding cross-peaks in the second 2D NOESY NMR spectrum. 17. The method of claim 15, wherein the step of determining comprises: comparing intensities of one or more cross-peaks in the first 2D NOESY NMR spectrum with intensities of one or more corresponding cross-peaks in the second 2D NOESY NMR spectrum. 18. The method of claim 15, wherein the first glycoprotein preparation is a therapeutic glycoprotein product. 19. The method of claim 15, wherein the first and second glycoprotein preparations were prepared by the same method. 20. The method of claim 15, wherein the first and second glycoprotein preparations were prepared by different methods. 21. The method of claim 15, wherein the one or more cross-peaks are the result of correlations between amide NH nuclei. 22. The method of claim 15, wherein the one or more cross-peaks are the result of correlations between amide NH nuclei and CH.sub.3 methyl nuclei. 23. The method of claim 15, wherein the one or more cross-peaks are the result of correlations between CH.sub.3 methyl nuclei. 24. The method of claim 15, wherein the one or more cross-peaks are the result of correlations between amide NH nuclei and indole NH nuclei. 25. The method of claim 15, wherein the one or more cross-peaks are the result of correlations between CH.sub.3 methyl nuclei and indole NH nuclei. 26. The method of claim 15, wherein the one or more cross-peaks are the result of correlations between amide NH nuclei and H-.alpha. nuclei. 27. The method of claim 15, wherein the one or more cross-peaks are the result of correlations between amide NH nuclei and glycosidic nuclei. 28. The method of claim 15 further comprising a step of assigning the one or more cross-peaks. 29. The method of claim 4, wherein the therapeutic glycoprotein product is a therapeutic antibody. 30. The method of claim 4, wherein the therapeutic glycoprotein product is alemtuzumab, etanercept, adalimumab, abatacept, infliximab, bevacizumab, rituximab, natalizumab, or cetuximab. 31. The method of claim 18, wherein the therapeutic glycoprotein product is a therapeutic antibody. 32. The method of claim 18, wherein the therapeutic glycoprotein product is alemtuzumab, etanercept, adalimumab, abatacept, infliximab, bevacizumab, rituximab, natalizumab, or cetuximab. 33. The method of claim 1, wherein the first preparation is a solution and the second preparation is a solution, and wherein the solution of the first preparation and the solution of the second preparation are substantially the same. 34. The method of claim 15, wherein the first preparation is a solution and the second preparation is a solution, and wherein the solution of the first preparation and the solution of the second preparation are substantially the same. |
Details for Patent 9,182,467
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 |
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