Bristol-Myers Squibb Company v. Teva Pharmaceuticals USA, Inc., 752 F.3d 967

BMS owns the ’244 patent; claim 8 covers entecavir for hepatitis B as a nucleoside analog with a carbocyclic ring and guanine base.
Entecavir differs from deoxyguanosine by an exocyclic methylene at the 5’ position; it is an effective hepatitis B treatment marketed as Baraclude.
Teva filed an ANDA with Paragraph IV certifications alleging non-infringement or invalidity; BMS sued Teva for infringement.
The district court held claim 8 invalid as obvious, based on 2′-CDG as a lead compound and a small, conservative modification to obtain entecavir, considering the total prior art.
Prior art shows 2′-CDG as a lead antiviral for herpes and hepatitis B, with several researchers treating it as a promising compound and noting activity and safety in the relevant period.
On appeal, this court affirmed the district court’s obviousness ruling, including findings on the lead compound, modification, and secondary considerations.

Issue	Plaintiff's Argument	Defendant's Argument	Held
Was claim 8 obvious over prior art?	BMS argues entecavir required non-trivial design choices not readily suggested by prior art.	Teva asserts 2′-CDG was a lead compound; minor modification yields entecavir, making it obvious.	Yes; claim 8 is obvious.
Was 2′-CDG properly identified as the lead compound?	BMS contends 2′-CDG was not a suitable lead or too toxic to be a lead.	Teva contends 2′-CDG was the natural lead in carbocyclic antivirals and widely used as such.	Yes; district court properly found 2′-CDG as the lead compound.
Do secondary considerations support nonobviousness?	BMS argues commercial success, long-felt need, and unexpected results weigh against obviousness.	Teva argues the secondary considerations do not overcome the strong prima facie case of obviousness.	Secondary considerations do not overcome obviousness; mixed but not sufficient to negate it.
Did the court err in the comparison basis for unexpected results?	BMS asserts improper comparison to the market drug rather than closest prior art and improper reliance on inventor’s knowledge.	Teva argues the district court correctly compared to 2′-CDG and used ordinary skilled-art reasoning.	No reversible error; comparisons were proper and still support obviousness.

KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (U.S. 2007) (obviousness framework; motivation to combine with reasonable expectation of success)
Graham v. John Deere Co., 383 U.S. 1 (U.S. 1966) (foundation for obviousness analysis)
Procter & Gamble Co. v. Teva Pharms. USA, Inc., 566 F.3d 989 (Fed. Cir. 2009) (clear-and-convincing standard; evidence required to prove obviousness)
Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350 (Fed. Cir. 2007) (lead compound concept and motivation to modify)
Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353 (Fed. Cir. 2008) (structural similarity and expectations of similar properties)
Altana Pharma AG v. Teva Pharms. USA, Inc., 566 F.3d 999 (Fed. Cir. 2009) (lead compound and close relationship in prior art)
Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280 (Fed. Cir. 2012) (reason to modify from lead compound based on prior art)
In re Cyclobenzaprine Hydrochloride Patent Litig., 676 F.3d 1063 (Fed. Cir. 2012) (finite number of paths to lead compound; small changes to try)
In re Dillon, 919 F.2d 688 (Fed. Cir. 1990) (unanticipated properties do not alone defeat obviousness)
Amgen Inc. v. Hoffman-LaRoche, 580 F.3d 1340 (Fed. Cir. 2009) (consideration of secondary considerations in obviousness)