Claims for Patent: 9,193,787

Summary for Patent: 9,193,787

Title:	Human antibodies that bind human TNF-alpha and methods of preparing the same
Abstract:	Methylglyoxal (MGO)-modified recombinant TNF-alpha antibodies (e.g., Adalimumab) are identified. MGO modification decreases binding between Adalimumab and TNF-alpha. Methods are disclosed for reducing the presence of MGO-modified antibodies in the production of Adalimumab TNF-alpha antibodies.
Inventor(s):	Chumsae; Christopher M. (North Andover, MA)
Assignee:	ABBVIE INC. (North Chicago, IL)
Application Number:	14/522,535
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,193,787
Patent Claims:	1. A method for purifying a composition comprising adalimumab, the method comprising: (a) contacting a cation exchange adsorbent with a composition comprising adalimumab and adalimumab comprising one or more methylglyoxal (MGO)-modified arginine amino acids at position 30 (R30) of SEQ ID NO. 1, position 93 (R93) of SEQ ID NO. 1, position 108 (R108) of SEQ ID NO. 1, position 16 (R16) of SEQ ID NO. 2, position 259 (R259) of SEQ ID NO. 2, position 359 (R359) of SEQ ID NO. 2, or position 420 (R420) of SEQ ID NO. 2; (b) removing adalimumab comprising one or more methylglyoxal (MGO)-modified arginine amino acids from the cation exchange adsorbent; and (c) subsequently eluting the adalimumab from the cation exchange adsorbent using an elution buffer. 2. The method of claim 1 wherein the composition of step (a) comprises adalimumab comprising a methylglyoxal (MGO)-modified arginine amino acid at position 30 (R30) of SEQ ID NO. 1. 3. The method of claim 1 wherein the composition of step (a) comprises adalimumab comprising a methylglyoxal (MGO)-modified arginine amino acid at position 93 (R93) of SEQ ID NO. 1. 4. The method of claim 1 wherein the composition of step (a) comprises adalimumab comprising a methylglyoxal (MGO)-modified arginine amino acid at position 108 (R108) of SEQ ID NO. 1. 5. The method of claim 1 wherein the composition of step (a) comprises adalimumab comprising a methylglyoxal (MGO)-modified arginine amino acid at position 16 (R16) of SEQ ID NO. 2. 6. The method of claim 1 wherein the composition of step (a) comprises adalimumab comprising a methylglyoxal (MGO)-modified arginine amino acid at position 259 (R259) of SEQ ID NO. 2. 7. The method of claim 1 wherein the composition of step (a) comprises adalimumab comprising a methylglyoxal (MGO)-modified arginine amino acid at position 359 (R359) of SEQ ID NO. 2. 8. The method of claim 1 wherein the composition of step (a) comprises adalimumab comprising a methylglyoxal (MGO)-modified arginine amino acid at position 420 (R420) of SEQ ID NO. 2. 9. The method of claim 1 wherein the adalimumab and adalimumab comprising one or more methylglyoxal (MGO)-modified arginine amino acids are expressed in Chinese hamster ovary cells using chemically defined media. 10. The method of claim 1 wherein at least 90% of the adalimumab comprising one or more methylglyoxal (MGO)-modified arginine amino acids is removed in step (b). 11. The method of claim 1 wherein at least 99% of the adalimumab comprising one or more methylglyoxal (MGO)-modified arginine amino acids is removed in step (b). 12. The method of claim 1 wherein a loading buffer having a pH lower than the pI of the elution buffer of step (c) is used in contacting step (a). 13. The method of claim 12 wherein the loading buffer has a pH ranging from about 5.5 to about 7.5, and the loading buffer is selected from the group consisting of sodium chloride/Tris-acetate, Tris-acetate, Ammonium sulfate/Tris-acetate, arginine/Tris-acetate, and any combination thereof. 14. The method of claim 1 wherein the elution buffer is selected from the group consisting of sodium chloride/Tris-acetate, Tris-acetate, Ammonium sulfate/Tris-acetate, arginine/Tris-acetate, and any combination thereof, and wherein said elution buffer comprises a salt at a concentration ranging from about 20 mM to about 200 mM. 15. The method of claim 14 wherein the salt in the elution buffer is sodium chloride. 16. The method of claim 14 wherein the pH of the elution buffer is between 5.5 and 9.0. 17. The method of claim 1 wherein the adalimumab comprising one or more methylglyoxal (MGO)-modified arginine amino acids is removed in step (b) using a wash buffer. 18. The method of claim 17 wherein the wash buffer is the same chemical species as the loading buffer. 19. The method of claim 17 wherein the conductivity of the elution buffer is higher than the conductivity of the wash buffer. 20. A method for purifying a composition comprising adalimumab, the method comprising: (a) contacting a cation exchange adsorbent with a composition comprising adalimumab and adalimumab comprising one or more hydroxylimidines at position 30 (R30) of SEQ ID NO. 1, position 93 (R93) of SEQ ID NO. 1, position 108 (R108) of SEQ ID NO. 1, position 16 (R16) of SEQ ID NO. 2, position 259 (R259) of SEQ ID NO. 2, position 359 (R359) of SEQ ID NO. 2, or position 420 (R420) of SEQ ID NO. 2; (b) removing adalimumab comprising one or more hydroxylimidines from the cation exchange adsorbent; and (c) subsequently eluting the adalimumab from the cation exchange adsorbent using an elution buffer. 21. The method of claim 20 wherein the composition of step (a) comprises adalimumab comprising a hydroxylimidine at position 30 (R30) of SEQ ID NO. 1. 22. The method of claim 20 wherein the adalimumab and adalimumab comprising one or more hydroxylimidines are expressed in Chinese hamster ovary cells using chemically defined media. 23. The method of claim 20 wherein at least 90% of the adalimumab comprising one or more hydroxylimidines is removed in step (b). 24. The method of claim 20 wherein at least 99% of the adalimumab comprising one or more hydroxylimidines is removed in step (b). 25. A method for purifying a composition comprising adalimumab, the method comprising: (a) contacting a cation exchange adsorbent with a composition comprising adalimumab and adalimumab comprising one or more hydroimidazolones at position 30 (R30) of SEQ ID NO. 1, position 93 (R93) of SEQ ID NO. 1, position 108 (R108) of SEQ ID NO. 1, position 16 (R16) of SEQ ID NO. 2, position 259 (R259) of SEQ ID NO. 2, position 359 (R359) of SEQ ID NO. 2, or position 420 (R420) of SEQ ID NO. 2; (b) removing adalimumab comprising one or more hydroimidazolones from the cation exchange adsorbent; and (c) subsequently eluting the adalimumab from the cation exchange adsorbent using an elution buffer. 26. The method of claim 25 wherein the composition of step (a) comprises adalimumab comprising a hydroimidazolone at position 30 (R30) of SEQ ID NO. 1. 27. The method of claim 25 wherein the adalimumab and adalimumab comprising one or more hydroimidazolones are expressed in Chinese hamster ovary cells using chemically defined media. 28. The method of claim 25 wherein at least 90% of the adalimumab comprising one or more hydroimidazolones is removed in step (b). 29. The method of claim 25 wherein at least 99% of the adalimumab comprising one or more hydroxylimidines is removed in step (b).

Details for Patent 9,193,787

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2033-03-12
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2033-03-12
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2033-03-12
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	09/23/2014		2033-03-12
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	11/23/2015		2033-03-12
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	03/09/2016		2033-03-12
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	10/17/2016		2033-03-12