624 F.Supp.3d 436
D. Del.2022Background
- UTC owns NDA for Tyvaso® and holds U.S. Pat. Nos. 9,593,066 ("'066") and 10,716,793 ("'793"), which are listed in the Orange Book; Liquidia filed a 505(b)(2) NDA for LIQ861 (dry‑powder treprostinil) and sent Paragraph IV certifications.
- Bench trial after UTC sued under 35 U.S.C. § 271(e)(2); disputes focused on infringement and validity of asserted claims of the '066 (claims 1–3, 6, 8, 9) and '793 (claims 1, 4, 6, 7, 8) patents.
- Yonsung (Korea) manufactures the treprostinil sodium API (TN) used by Liquidia; Yonsung's DMF and Liquidia's NDA set storage at 2–8°C; Liquidia uses TN in its PRINT process to make LIQ861 bulk powder.
- UTC's infringement theory for the '066 patent was product‑by‑process: LIQ861 allegedly embodies a composition where impurities from prior alkylation/hydrolysis are reduced after salt formation and isolation; additional disputes concerned storage at "ambient temperature."
- For the '793 method patent, UTC alleged Liquidia induced infringement because LIQ861's proposed label directs administration of therapeutically effective single‑event doses (15–90 µg delivered in 1–3 breaths).
Issues
| Issue | Plaintiff's Argument | Defendant's Argument | Held |
|---|---|---|---|
| Infringement of '066 impurity limitation (claims 1–3) | UTC: TN02→TN shows increase then decrease in impurities; TN analytics represent impurities in final composition, so LIQ861 meets limitation | Liquidia: peaks/data not tied to impurities from BTO alkylation/hydrolysis; testing not of LIQ861 powder | Court: UTC proved by preponderance that TN impurities reflect reduction in impurities (claims 1–3 infringed) |
| Infringement of '066 storage at ambient temp (claim 6) | UTC: TN experienced ambient storage during warehouse, shipment, and PRINT Step 1 | Liquidia: NDA/DMF require 2–8°C; excursions were not used for GMP batches or were explained (data logger artifacts); "stored" need not be shipping; TN used under refrigerated conditions | Court: UTC failed to prove Liquidia will store TN at ambient temperature; no infringement of claim 6 |
| Infringement of '066 storing salt before preparing product (claims 8,9) | UTC: storage between PRINT steps and dry‑box use show storage after salt formation and before product prep | Liquidia: product preparation begins at PRINT Step 1; any interim handling is use, not storage | Court: UTC failed to prove storage-before‑preparation; claims 8 and 9 not infringed |
| Invalidity of '066 product‑by‑process claims (claims 1,2,3,6,9) — anticipation | Liquidia: 2004 Moriarty article discloses UT‑15 treprostinil made by alkylation/hydrolysis; claimed product is same as UT‑15 | UTC: claims include impurities/stability limitations that distinguish product | Court: Moriarty anticipates — claimed treprostinil free acid is structurally/ functionally the same; claims 1,2,3,6,9 invalid as anticipated (clear & convincing) |
| Induced infringement of '793 method claims (1,4,6,7,8) | UTC: LIQ861 label instructs 3–5×/day at claimed single‑event doses that are therapeutically effective (hemodynamic improvement); Liquidia knows patent and will promote/use label => specific intent | Liquidia: label lacks hemodynamic instructions/data and does not induce therapeutically effective single‑event dosing; later PTAB IPR invalidated '793 | Court: LIQ861 administration meets "therapeutically effective single‑event dose" and label will inevitably lead to infringement; UTC proved induced infringement by preponderance; PTAB FWD invalidating '793 is not final, so does not preclude district finding |
| Enablement / written description for '793 (dry powder/DPI scope) | Liquidia: claims sweep dry powder/DPI but specification lacks examples or guidance => not enabled / insufficient written description | UTC: specification discloses bolus dose, delivery parameters and POSA could, with routine techniques, make dry powder formulation; UTC's experiments developed suitable powders quickly | Court: Liquidia failed to prove lack of enablement or written description; dry powder/DPI scope enabled and described (clear & convincing not met) |
Key Cases Cited
- Markman v. Westview Instruments, 52 F.3d 967 (Fed. Cir. 1995) (en banc) (claim construction is a two‑step court task)
- Amgen Inc. v. F. Hoffmann‑La Roche Ltd., 580 F.3d 1340 (Fed. Cir. 2009) (product‑by‑process claims are judged on the product, not the process, absent structural/functional differences)
- Abbott Labs. v. TorPharm, Inc., 300 F.3d 1367 (Fed. Cir. 2002) (ANDA/Hatch‑Waxman infringement focuses on the product likely to be sold following FDA approval)
- Bai v. L & L Wings, Inc., 160 F.3d 1350 (Fed. Cir. 1998) (infringement is a question of fact)
- Commil USA, LLC v. Cisco Sys., Inc., 575 U.S. 632 (2015) (belief in invalidity is not a defense to induced infringement; if patent is invalid, there is no infringement)
- Fujitsu Ltd. v. Netgear Inc., 620 F.3d 1321 (Fed. Cir. 2010) (patentee must show specific instances or clear evidence of likely infringement in Hatch‑Waxman context)
- In re Thorpe, 777 F.2d 695 (Fed. Cir. 1985) (old product not patentable even if made by new process)
- Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010) (written description standard: specification must show possession of claimed invention)
- In re Wands, 858 F.2d 731 (Fed. Cir. 1988) (factors for assessing undue experimentation/enablement)
- Brown v. 3M, 265 F.3d 1349 (Fed. Cir. 2001) (claim covering alternatives anticipated if any alternative is in prior art)
- Sunovion Pharms. v. Teva Pharms. USA, 731 F.3d 1271 (Fed. Cir. 2013) (ANDA labeling can create literal infringement when ANDA seeks approval for products necessarily within claim scope)
- Vectura Ltd. v. GlaxoSmithKline LLC, 397 F. Supp. 3d 579 (D. Del. 2019) (comparative testing can support infringement when tested samples are representative)