A generic pharmaceutical’s FDA-approved label is a key factor in determining if marketing the generic pharmaceutical induces infringement of a patented method-of-treatment claim.

The Court of Appeals for the Federal Circuit (CAFC) most recently addressed the issue in Eli Lilly & Co. v. Teva Parenteral Meds., Inc. (Fed. Cir. No.: 15-2067), a Precedential Opinion published January 12, 2017. In reviewing the case, the Federal Circuit panel, compared two earlier cases:  AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042 (Fed. Cir. 2010) and Takeda Pharmaceuticals U.S.A., Inc. v. West-Ward Pharmaceutical Corp., 785 F.3d 625 (Fed. Cir. 2015).

Eli Lilly v. Teva — Pemetrexed Disodium (ALIMTA®)

Eli Lilly markets pemetrexed disodium, a chemotherapy drug, under the brand name ALIMTA®. Teva submitted an Abbreviated New Drug Application (ANDA) seeking approval by the Food and Drug Administration (FDA) to market generic versions of ALIMTA®. Teva submitted Paragraph IV certifications under 21 U.S.C. § 355(j)(2)(A)(vii)(IV), declaring that Eli Lilly’s US Patent No. 7,772,209, issued in 2010, was invalid, unenforceable, or would not be infringed.  Eli Lilly subsequently brought a consolidated action against Teva for infringement under 35 U.S.C. § 271(e)(2).  The United States District Court for the Southern District of Indiana found direct infringement attributable to physicians and held Teva liable for inducing the physicians’ infringement because Teva’s product labeling would inevitably lead some physicians to infringe Eli Lilly’s patent.  The CAFC affirmed the District Court’s decision.

Eli Lilly’s patent claims methods of administering the chemotherapy drug pemetrexed disodium pemetrexed after pretreatment with common vitamins—folic acid and vitamin B12. Pemetrexed is an antifolate that kills cancer cells by inhibiting the function of folates, a class of nutrients necessary for cell reproduction. Physicians therefore prescribe pemetrexed to treat certain types of lung cancer and mesothelioma. The vitamin pre-treatments reduce the toxicity of pemetrexed.

CAFC Analysis & Decision

Teva’s FDA label spelled out the method claimed in Eli Lilly’s patent.  Moreover, the parties agreed that Teva’s product labeling would be materially the same as Eli Lilly’s ALIMTA® product labeling.  Importantly, both FDA labels provided instructions regarding the administration of folic acid including repeated instructions and warnings regarding the importance of and reasons for folic acid pre-treatment.  The District Court therefore found that the label’s instructions and warnings would inevitably lead some physicians to infringe Eli Lilly’s patent.  The Federal Circuit decided that the District Court did not clearly err because Teva’s pursuit of the FDA label was enough evidence establishing Teva’s requisite intent for inducement.

Comparison to Takeda case:

Takeda Pharmaceuticals U.S.A., Inc. v. West-Ward Pharmaceutical Corp., 785 F.3d 625 (Fed. Cir. 2015).

• Takeda’s sells Colcrys®, colchicine for treating acute gout flares.
• Hikma/West Ward launched the generic Mitigare®, colchicine for prophylactically treating gout.
• Hikma /West Ward did not infringe Takeda’s patent because Hikma’s FDA label for prophylactic treatment did not describe Takeda’s method claim for acute treatment.
• Subsequent litigation: After losing its appeal, Takeda filed an amended claim in Delaware. Then on May 16, 2016 (No. Civ. No. 14‑1268‑SLR) the Delaware District Court granted grants Hikma’s [West Ward] motion to dismiss.

Comparison to AstraZeneca case:

• In the AstraZeneca case, the CAFC held that a label that instructed users to follow the instructions in an infringing manner was sufficient, even though some users would not follow the instructions because the product in question had substantial non-infringing uses.
• A defendant’s decision to continue seeking FDA approval of instructions that teach an infringing use is sufficient evidence of specific intent to induce infringement.

Quotes Regarding Induced Infringement:

• “Mere knowledge of the facts alleged to constitute infringement is not sufficient” (DSU Med.  471 F.3d at 1305).
• When the alleged inducement relies on a drug label’s instructions, “[t]he question is not just whether [those] instructions describ[e] the infringing mode, . . . but whether the instructions teach an infringing use such that we are willing to infer from those instructions an affirmative intent to infringe the patent.” Takeda, 785 F.3d at 631 (internal quotation marks omitted).
• “The label must encourage, recommend, or promote infringement.” For purposes of inducement, “it is irrelevant that some users may ignore the warnings in the proposed label.”  AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1060 (Fed. Cir. 2010).
• The accused indirect infringer must have “knowingly aided and abetted” direct infringement. Warner‑Lambert v. Apotex, 316 F.3d 1348 (Fed. Cir. 2003)
• The CAFC stated in Warner‑Lambert in the ANDA context, it is well-established that “mere knowledge of possible infringement by others does not amount to inducement; specific intent and action to induce infringement must be proven.” Warner-Lambert v. Apotex, 316 F.3d 1348 at 1364  (Fed. Cir. 2003) (citation omitted).
• “The Hatch-Waxman Act was designed to enable the sale of drugs for non‑patented uses even though this would result in some off-label infringing uses.” See Caraco, 132 S.Ct. at 1681-82 (“Congress understood [that] a single drug may have multiple methods of use, only one or some of which a patent covers” and that the statute “contemplates that one patented use will not foreclose marketing a generic drug for other unpatented ones.”);
• The Hatch-Waxman Act was not intended “as a sword against any competitor’s ANDA seeking approval to market an off-patent drug for an approved use not covered by the patent.” (Warner-Lambert v. Apotex, 316 F.3d 1348 at 1359)