Grunenthal Gmbh v. Alkem Laboratories Limited
919 F.3d 1333
Fed. Cir.2019Background
- Grünenthal owns U.S. Patents No. 7,994,364 (the ’364 patent, claiming Form A polymorph of tapentadol hydrochloride and its use) and No. 8,536,130 (the ’130 patent, claiming methods of treating polyneuropathic pain). Depomed is exclusive licensee; patents are listed for NUCYNTA® ER.
- Prior art disclosed tapentadol hydrochloride and a single crystalline form (Form B) in the ’737 patent; polymorphism of tapentadol hydrochloride was unknown before the ’364 filing.
- Byrn (1995) is prior art describing a general polymorph–screening decision tree (lists solvents and variables to vary) but gives no specific enabling conditions to produce particular polymorphs.
- Alkem, Hikma, and Actavis filed ANDAs to market generic tapentadol products; they stipulated infringement of the ’364 patent but challenged validity (obviousness, utility) and Hikma/Actavis contested infringement of the ’130 patent.
- District court found: no induced or contributory infringement of the ’130 patent by Hikma/Actavis (labels did not specifically encourage treatment of polyneuropathic pain); ’364 patent not invalid for obviousness and has sufficient utility. Court split on infringement of ’130 as to Alkem vs. others; appeals followed.
Issues
| Issue | Plaintiff's Argument (Grünenthal/Depomed) | Defendant's Argument (Alkem/Hikma/Actavis) | Held |
|---|---|---|---|
| Induced infringement of ’130 by Hikma/Actavis | Labels for chronic severe pain will cause some physicians to use product for polyneuropathic pain (thus induce infringement) | Labels do not specifically instruct or recommend treatment of polyneuropathic pain; ANDA carve-outs and no DPN indication; therefore no specific intent | No induced infringement: labels do not encourage the patented method; specific intent not shown |
| Contributory infringement of ’130 | Generic products will be used substantially for polyneuropathic pain | There are substantial noninfringing uses (nociceptive/mononeuropathic chronic pain); physicians routinely prescribe for non-polyneuropathic indications | No contributory infringement: district court credibility findings supporting substantial noninfringing uses affirmed |
| Obviousness of ’364 (Form A) over prior art (’737 + Byrn) | Byrn’s polymorph screening + ’737’s compound disclosure would motivate and give reasonable expectation to find Form A (obvious to try) | Byrn is general; it lists many solvents/variables but supplies no specific guidance; polymorphism unknown; no reasonable expectation of success | ’364 not obvious: no reasonable expectation of success and Byrn does not provide a finite, predictable route to Form A |
| Utility of ’364 (specific and substantial) | Specification’s statements about stability are conclusory; need test data to show superior stability and specific utility | Form A is disclosed as useful to treat pain; prior art establishes analgesic activity; Example 16 shows reversible temp-dependent Forms and supports ambient stability | Utility satisfied: disclosure plus Example 16 and prior art pharmacological activity show specific and substantial utility; district court’s finding not clearly erroneous |
Key Cases Cited
- SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331 (Fed. Cir.) (bench-trial review standards for factual findings)
- AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042 (Fed. Cir.) (label instructions can infer intent to induce if they instruct users to perform patented method)
- Takeda Pharm. U.S.A., Inc. v. West-Ward Pharm. Corp., 785 F.3d 625 (Fed. Cir.) (inducement requires specific intent to encourage infringement)
- KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (U.S.) (obvious-to-try framework and requirement of finite, predictable solutions)
- Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir.) (reasonable expectation of success where prior art narrows choices predictably)
- Cubist Pharm., Inc. v. Hospira, Inc., 805 F.3d 1112 (Fed. Cir.) (obviousness where known techniques predictably achieve claimed purity)
- In re Fisher, 421 F.3d 1365 (Fed. Cir.) (utility requires specific and substantial benefit)
- Fujikawa v. Wattanasin, 93 F.3d 1559 (Fed. Cir.) (pharmacological activity can establish utility)