COHERUS FILES FOUR IPR PETITIONS AGAINST HUMIRA BUFFER-LESS PATENT

            Coherus BioSciences, Inc. filed four IPR petitions against a single Humira patent, U.S. Patent No. 9,085,619.  (IPR2017-00822, IPR2017-00823, IPR2017-00826, and IPR2017-00827).  At first glance, one might think that the ‘619 Patent is a crucial patent since Coherus filed four IPR petitions against the ‘619 Patent.  However, the ‘619 patent is not on the list of Humira patents that Abbvie alleged Amgen’s Humira biosimilar (Amjevita) infringed. 

            Independent claim 16 of the ’619 Patent covers formulations of adalimumab (Humira) in water without a “buffering system.”  According to Coherus, it was known for decades that a protein, by itself, can provide buffer capacity and that a protein’s buffer capacity comes from the acidic or basic side chains of certain of its constituent amino acids.

            Coherus relies on a different ground of invalidity in each IPR petition.  In IPR2017-00822, Coherus argues that Gokarn PCT (WO 2006/138181) teaches the use of adalimumab in self buffering formulations—i.e., “in the absence of other buffers.”  According to Coherus, the Gokarn PCT also teaches that in a most preferred embodiment, the protein (e.g., adalimumab) provides “at least approximately 99% of the buffer capacity of the composition.”  Additional prior art relied on by Coherus in its petitions include the 2003 Humira^® Label, Fransson (J. Pharm. Pharmacol., 48:1012-1015 (1996)), the 2005 Gamimune^® Label, Gokarn provisional patent application (No. 60/690,582) (relied on as a 102e references), and Gokarn U.S. 2016/0319011.

            In IPR2017-00822, Coherus provides the following claim chart to prove that the claims of the ‘619 Patent are anticipated in view of the Gokarn PCT:

U.S. Patent No. 9,085,619	Gokarn PCT (WO 2006/138181)
Claim 16. An aqueous pharmaceutical formulation comprising:	The preamble is non-limiting. "[T]he invention provides self-buffering pharmaceutical protein formulations that are suitable for veterinary and human medical use."
(a) an anti-tumor necrosis factor alpha antibody comprising a light chain variable region (LCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:3, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:5, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7, and a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO:8,	"wherein the protein is selected from the group consisting of ... HUMIRA (adalimumab) .... Adalimumab comprises these sequences. This is further demonstrated by claim 18, which is dependent on claim 16 and recites adalimumab.
wherein the concentration of the antibody is 50 to 200 mg/ml; and	"HUMIRA (adalimumab)" discloses 50 mg/mL. "[W]herein the concentration of the protein is between approximately ... 20 and 200 ... mg/ml."
	"[W]herein the concentration of the protein is between approximately 20 and 400 mg/ml.
(b) water;	"[F]ormulations of self-buffering proteins comprise a protein and a carrier… In preferred embodiments ... the carrier is a liquid.... Liquid carriers may be organic or non-organic. Preferably they are aqueous, most preferably are largely or entirely comprised of pure water."
wherein the formulation does not comprise a buffering system.	"The self-buffering protein formulations are substantially free of other buffering agents  ... "Self-buffering' means the capacity of a substance, such as a pharmaceutical protein, to resist change in pH sufficient for a given application, in the absence of other buffers. "the protein provides ... very highly especially particularly preferably at least approximately 99% of the buffer capacity of the composition"  Claim 5 refers to "pH maintained by the buffering action of the protein .... "
Claim 17. The formulation of claim 16, wherein the antibody comprises a LCVR comprising the amino acid sequence set forth in SEQ ID NO: 1, and a HCVR comprising the amino acid sequence set forth in SEQ ID NO: 2.	"Wherein the protein is selected from the group consisting of ... HUMIRA (adalimumab) .... Adalimumab comprises these sequences. This is further demonstrated by claim 18, which is dependent on claim 17 and recites adalimumab.
Claim 18. The formulation of claim 17, wherein the antibody is adalimumab.	"Wherein the protein is selected from the group consisting of ... HUMIRA (adalimumab)
Claim 19. The formulation of claim 16, wherein the formulation further comprises a non-ionizable excipient.	"One or more of sorbitol, mannitol, sucrose .... "  "polysorbate 80." Claim 23, which depends from claim 9 ("requiring one or more pharmaceutically acceptable polyols").  As evidenced by Claim 10, such polyols include mannitol and sucrose.
Claim 24. The formulation of claim 16, wherein the pH of the formulation is from 4 to 8.	"HUMIRA (adalimumab)" discloses pH 5.2. Claim 23, which depends from claim 5 (requiring "the pH maintained by the buffering action of the protein is between approximately  3.5 to 8.")
Claim 25. The formulation of claim 16, wherein the pH of the formulation is from 4 to 6.	See above for claim 24. Further, "the pH maintained by the buffering action of the protein is between approximately ... 4.0 to 6.0…..
Claim 26. The formulation of claim 16, wherein the pH of the formulation is from 5 to 6.	See above for claims 24-25. Further, the Gokam PCT demonstrates that a variety of antibodies possess significant buffering capacity in the pH range 5.0 to 6.0.
Claim 27. The formulation of claim 18, wherein the pH of the formulation is from 4 to 8.	"HUMlRA (adalimumab)" discloses pH 5.2. Claim 23, which depends from claim 5 (requiring "the pH maintained by the buffering action of the protein is between approximately…4.0 to 6.0...