Claims for Patent: 9,505,833

Summary for Patent: 9,505,833

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 MOO-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:	14/078,181
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,505,833
Patent Claims:	1. A composition comprising adalimumab and methylglyoxal (MGO)-modified forms of adalimumab, wherein said composition was expressed in Chinese Hamster Ovary (CHO) cells cultured in chemically defined media (CDM), wherein said MGO-modified forms of adalimumab comprise a MGO-modified arginine amino acid at one or more of positions 30 (R30) of SEQ ID NO. 1, 93 (R93) of SEQ ID NO. 1, 108 (R108) of SEQ ID NO. 1, 16 (R16) of SEQ ID NO. 2, 259 (R259) of SEQ ID NO. 2, 359 (R359) of SEQ ID NO. 2, and 420 (R420) of SEQ ID NO. 2, and wherein said composition was purified by ion exchange chromatography such that said MGO-modified forms of adalimumab in said composition comprise less than about 1% of the total amount of adalimumab and MGO-modified forms of adalimumab. 2. The composition of claim 1, wherein said MGO-modified arginine amino acid is at position 30 (R30) of SEQ ID NO. 1. 3. The composition of claim 1, wherein said MGO-modified arginine amino acid is at position 93 (R93) of SEQ ID NO. 1. 4. The composition of claim 1, wherein said MGO-modified arginine amino acid is at position 108 (R108) of SEQ ID NO. 1. 5. The composition of claim 1, wherein said MGO-modified arginine amino acid is at position 16 (R16) of SEQ ID NO. 2. 6. The composition of claim 1, wherein said MOO-modified arginine amino acid is at position 259 (R259) of SEQ ID NO. 2. 7. The composition of claim 1, wherein said MGO-modified arginine amino acid is at position 359 (R359) of SEQ ID NO. 2. 8. The composition of claim 1, wherein said MGO-modified arginine amino acid is at position 420 (R420) of SEQ ID NO. 2. 9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a composition according to claim 1. 10. The pharmaceutical composition of claim 9, wherein said MOO-modified arginine amino acid is at position 30 (R30) of SEQ ID NO. 1. 11. The composition of claim 1, wherein said adalimumab dissociates from human TNF-alpha with a K.sub.off rate constant of 1.times.10.sup.-3 s.sup.-1 or less, as determined by surface plasmon resonance. 12. The composition of claim 1, wherein said MGO-modified forms of adalimumab exhibit decreased binding affinity to human TNF-alpha as compared to the binding affinity exhibited by unmodified adalimumab, as measured by surface plasmon resonance. 13. The composition of claim 12, wherein said MGO-modified forms of adalimumab exhibit a binding affinity to human TNF-alpha at least about three times less than the binding affinity exhibited by unmodified adalimumab, as measured by surface plasmon resonance. 14. The composition of claim 13, wherein said MGO-modified arginine amino acid is at position 30 (R30) of SEQ ID NO. 1. 15. A composition comprising adalimumab and methylglyoxal (MGO)-modified forms of adalimumab, wherein said composition was expressed in Chinese Hamster Ovary (CHO) cells cultured in chemically defined media (CDM), wherein said MGO-modified forms of adalimumab comprise a hydroxylimidine, hydroimidazolone, or combinations thereof at one or more of positions 30 (R30) of SEQ ID NO. 1, 93 (R93) of SEQ ID NO. 1, 108 (R108) of SEQ ID NO. 1, 16 (R16) of SEQ ID NO. 2, 259 (R259) of SEQ ID NO. 2, 359 (R359) of SEQ ID NO. 2, and 420 (R420) of SEQ ID NO. 2, and wherein said composition was purified by ion exchange chromatography such that said MGO-modified forms of adalimumab in said composition comprise less than about 1% of the total amount of adalimumab and MGO-modified forms of adalimumab. 16. The composition of claim 15, wherein said MGO-modified forms of adalimumab comprise a hydroxylimidine at one or more of positions 30 (R30) of SEQ ID NO. 1, 93 (R93) of SEQ ID NO. 1, 108 (R108) of SEQ ID NO. 1, 16 (R16) of SEQ ID NO. 2, 259 (R259) of SEQ ID NO. 2, 359 (R359) of SEQ ID NO. 2, and 420 (R420) of SEQ ID NO. 2. 17. The composition of claim 16, wherein said hydroxylimidine is at position 30 (R30) of SEQ ID NO. 1. 18. The composition of claim 15, wherein said MGO-modified forms of adalimumab, comprise a hydroimidazolone at one or more of positions 30 (R30) of SEQ ID NO. 1, 93 (R93) of SEQ ID NO. 1, 108 (R108) of SEQ ID NO. 1, 16 (R16) of SEQ ID NO. 2, 259 (R259) of SEQ ID NO. 2, 359 (R359) of SEQ ID NO. 2, and 420 (R420) of SEQ ID NO. 2. 19. The composition of claim 18, wherein said hydroimidazolone is at position 30 (R30) of SEQ ID NO. 1.

Details for Patent 9,505,833

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