Liquidia Technolgies Inc v. United Therapeutics Corp

1. Case Identification

• Case #: IPR2020-00770
• Patent #: 9,604,901
• Filed: March 30, 2020
• Petitioner(s): Liquidia Technologies, Inc.
• Patent Owner(s): United Therapeutics Corporation
• Challenged Claims: 1-9

2. Patent Overview

• Title: Process to Prepare Treprostinil, the Active Ingredient in Remodulin®
• Brief Description: The ’901 patent is directed to product-by-process claims for a pharmaceutical batch of treprostinil or a salt thereof. The claimed process involves alkylating a benzindene triol, hydrolyzing the resulting product to form a solution of treprostinil, contacting the solution with a base to form a salt, and isolating the salt.

3. Grounds for Unpatentability

Ground 1: Obviousness over Phares - Claims 1-9 are obvious over Phares.

• Prior Art Relied Upon: Phares (WO 2005/007081).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Phares discloses all elements of the claimed invention. Phares describes the synthesis of treprostinil and its diethanolamine salt, which are structurally identical to the products of the ’901 patent. Phares teaches a synthetic route starting from a benzindene triol (an enantiomer of the ’901 patent's precursor), alkylating it using the same reagents (chloroacetonitrile, K2CO3), and hydrolyzing the intermediate to produce treprostinil acid. Phares further discloses reacting the treprostinil acid with the specific base diethanolamine, isolating the resulting salt in crystalline forms (Form A and Form B), and preparing therapeutically effective pharmaceutical compositions. Petitioner contended that scaling up the gram-scale reactions taught in Phares to meet the "at least 2.9 g" limitation of claim 1 would have been a routine and obvious modification for a POSITA.
  • Motivation to Combine (for §103 grounds): This ground is based on a single reference. Petitioner argued that a POSITA would have been motivated to apply the well-known purification and salt formation steps taught in Phares to prepare stable, pharmaceutical-grade batches of treprostinil. Petitioner asserted that combining the hydrolysis solution directly with the base, rather than first isolating the treprostinil acid, was an obvious process simplification to save a step, time, and cost.
  • Expectation of Success: A POSITA would have had a high expectation of success in applying the teachings of Phares because all recited steps involve standard, predictable organic chemistry reactions and purification techniques that are well-established in the art.

Ground 2: Obviousness over Moriarty in combination with Phares - Claims 1-9 are obvious over Moriarty in view of Phares.

• Prior Art Relied Upon: Moriarty (a 2004 journal article on the synthesis of Treprostinil) and Phares (WO 2005/007081).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Moriarty discloses an efficient, large-scale (producing 441 g) synthesis of high-purity treprostinil acid, the very product claimed in the ’901 patent. Moriarty's process explicitly teaches the key claimed steps of alkylating a benzindene triol and hydrolyzing the resulting intermediate. While Moriarty produces the treprostinil acid, Phares teaches the subsequent steps of reacting that acid with diethanolamine to form the specific treprostinil diethanolamine salt and preparing it as a pharmaceutical product. The combination of Moriarty's synthesis with Phares's salt formation and formulation teachings allegedly discloses every limitation of claims 1-9.
  • Motivation to Combine: A POSITA would combine these references to create an improved pharmaceutical product. Specifically, a POSITA would start with Moriarty’s well-known and efficient process for making treprostinil acid and then apply Phares’s teachings to convert it into a more stable and pharmaceutically desirable diethanolamine salt. The motivation would be to leverage a known, scalable synthesis process (Moriarty) to produce the starting material for a known method of improving the final product form (Phares).
  • Expectation of Success: A POSITA would have a reasonable expectation of success, as the combination involves using a known synthetic product (treprostinil acid from Moriarty) as the starting material for a known and straightforward salt formation reaction disclosed by Phares for that exact same molecule.

4. Key Technical Contentions (Beyond Claim Construction)

• Petitioner's central technical argument was that the '901 patent's claims are product-by-process claims, for which patentability hinges on the novelty and non-obviousness of the final product, not the process of making it. Petitioner contended that the claimed process—even if slightly different from the prior art—does not produce a treprostinil product that is structurally or functionally distinct from the treprostinil and treprostinil diethanolamine salt products already disclosed by Phares and Moriarty.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be improper. Petitioner acknowledged that the Examiner considered both Moriarty and Phares during prosecution. However, Petitioner contended that the Examiner made a significant error by not having the benefit of the Final Written Decision (FWD) from a parallel IPR (IPR2016-00006) on the parent ’393 patent. In that proceeding, the PTAB invalidated substantively identical claims based on the same prior art (Moriarty and Phares), reaching a conclusion directly opposite to the Examiner’s allowance of the ’901 patent. Therefore, the petition presented arguments and evidence in a new light that the Examiner had misapprehended or overlooked.

6. Relief Requested

• Petitioner requests institution of inter partes review and cancellation of claims 1-9 of Patent 9,604,901 as unpatentable.