DCT
1:20-cv-00755
United Therap Corp v. Liquidia Tech Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: United Therapeutics Corporation (Delaware)
- Defendant: Liquidia Technologies Inc (Delaware)
- Plaintiff’s Counsel: Morris Nichols Arsht & Tunnell LLP; Wilson Sonsini Goodrich & Rosati; Boies Schiller & Flexner LLP
- Case Identification: 1:20-cv-00755, D. Del., 07/22/2020
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is a Delaware corporation with a registered agent in the state.
- Core Dispute: Plaintiff alleges that Defendant's submission of a New Drug Application to the FDA for a generic version of Plaintiff's TYVASO® product constitutes an act of infringement of three U.S. patents.
- Technical Context: The technology concerns pharmaceutical compositions and methods related to treprostinil, a prostacyclin vasodilator used for the treatment of pulmonary arterial hypertension.
- Key Procedural History: The action was triggered by Defendant’s submission of a New Drug Application under § 505(b)(2) of the Food, Drug and Cosmetic Act, and a "Paragraph IV" certification asserting that Plaintiff's patents are invalid, unenforceable, or would not be infringed. Subsequent to the filing of this complaint, two of the patents-in-suit underwent Inter Partes Review (IPR) at the U.S. Patent and Trademark Office. IPR proceedings resulted in the cancellation of all claims of U.S. Patent No. 10,716,793 and the cancellation of claims 1-5, 8, and 9 of U.S. Patent No. 9,604,901, significantly impacting the potential scope of the present litigation, pending any appeals.
Case Timeline
| Date | Event |
|---|---|
| 2006-05-15 | ’793 Patent Priority Date |
| 2007-12-17 | ’066 and ’901 Patents Priority Date |
| 2009-07-01 | Plaintiff's TYVASO® initially approved by FDA |
| 2017-03-14 | ’066 Patent Issue Date |
| 2017-03-28 | ’901 Patent Issue Date |
| 2020-04-24 | Defendant sent Notice Letter to Plaintiff |
| 2020-07-21 | ’793 Patent Issue Date |
| 2020-07-22 | Complaint Filing Date |
| 2021-01-07 | IPR filed against ’793 Patent |
| 2024-11-12 | IPR Certificate issues canceling all claims of '793 Patent |
| 2024-12-20 | IPR Certificate issues canceling claims 1-5, 8, 9 of '901 Patent |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,593,066, "Process to prepare treprostinil, the active ingredient in Remodulin®", Issued March 14, 2017
The Invention Explained
- Problem Addressed: The patent background describes a need for an efficient, large-scale process suitable for the commercial production of prostacyclin derivatives like treprostinil (Compl., Ex. A, ’066 Patent, col. 2:1-4).
- The Patented Solution: The invention provides an improved process to purify treprostinil by converting it to a salt, which can be more easily handled and purified than the free acid form. The abstract describes a process to "convert benzindene triol to treprostinil via salts of treprostinil and to purify treprostinil" (’066 Patent, Abstract; col. 8:46-67). This multi-step chemical synthesis is designed to increase yield and purity for pharmaceutical manufacturing.
- Technical Importance: This process claims to offer a more economical, safer, and higher-purity method for manufacturing a key active pharmaceutical ingredient, which is a critical consideration for commercial drug production (’066 Patent, col. 6:1-5).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims without specification (Compl. ¶36). Independent claim 8 is representative of the asserted process technology.
- Independent Claim 8 requires a process of preparing a pharmaceutical product that includes the steps of:
- alkylating a triol intermediate of a specific formula;
- hydrolyzing the resulting compound to form treprostinil;
- forming a salt of treprostinil that is stable at ambient temperature;
- storing the treprostinil salt at ambient temperature; and
- preparing a pharmaceutical product from the treprostinil salt after storage.
U.S. Patent No. 9,604,901, "Process to prepare treprostinil, the active ingredient in Remodulin®", Issued March 28, 2017
The Invention Explained
- Problem Addressed: Similar to its parent '066 patent, this patent addresses the need for an efficient, high-purity commercial synthesis process for treprostinil (Compl., Ex. B, ’901 Patent, col. 2:1-4).
- The Patented Solution: This patent claims a pharmaceutical batch of treprostinil or its salt, defined by the process used to make it. The claimed process involves forming and isolating a treprostinil salt as a purification step, which allegedly results in a final batch with fewer impurities than batches made by prior art methods (’901 Patent, col. 17:23-40, Claim 1). The invention focuses on the purity profile of the final product as a result of the specific manufacturing steps.
- Technical Importance: Achieving a high-purity pharmaceutical batch with a low level of impurities is essential for drug safety, efficacy, and obtaining regulatory approval.
Key Claims at a Glance
- The complaint asserts infringement of one or more claims without specification (Compl. ¶53). Independent claim 1 is a representative product-by-process claim.
- Independent Claim 1 claims:
- A pharmaceutical batch consisting of treprostinil or a salt thereof and impurities;
- Wherein the batch results from a process that includes (a) alkylating a benzindene triol, (b) hydrolyzing the product, (c) contacting the resulting solution with a base to form a salt, (d) isolating the salt, and (e) optionally reacting the salt with an acid to form treprostinil;
- Wherein the batch contains at least 2.9 g of treprostinil or its salt.
U.S. Patent No. 10,716,793, "Treprostinil Administration by Inhalation", Issued July 21, 2020
- Technology Synopsis: The patent addresses the need for a more convenient method of administering treprostinil for pulmonary hypertension (’793 Patent, col. 2:60-64). The invention is a method of treatment comprising administering a specific dose of treprostinil (15 to 90 micrograms) in a "single event" using a small number of inhalations (1 to 3 breaths), which can be achieved with a compact device like a metered dose inhaler (’793 Patent, col. 18:20-30, Claim 1). This method aims to provide patients with greater autonomy and ease of use compared to continuous infusion or nebulization therapies.
- Asserted Claims: The complaint asserts one or more claims without further specification (Compl. ¶70).
- Accused Features: The complaint alleges that Defendant's "Proposed Generic Product," which delivers treprostinil via a dry powder inhaler (DPI), infringes the ’793 patent (Compl. ¶6, ¶34, ¶70).
III. The Accused Instrumentality
Product Identification
- Liquidia’s Proposed Generic Product, a generic version of UTC's TYVASO® (treprostinil) Inhalation Solution, 0.6 mg/ml (Compl. ¶2).
Functionality and Market Context
- The accused product is designed for the treatment of pulmonary arterial hypertension (Compl. ¶25). It delivers the active pharmaceutical ingredient, treprostinil, using a dry powder inhaler (DPI) device (Compl. ¶6).
- The complaint alleges, on information and belief, that the product is intended to deliver treprostinil in capsules containing between 26.5 and 106 micrograms (mcgs) each, for total doses ranging from 26.5 to 212 mcgs, and that the contents of a capsule can be inhaled in "1-2 breaths" (Compl. ¶34).
- The product is the subject of a § 505(b)(2) New Drug Application submitted to the FDA, through which Liquidia seeks approval to market a generic competitor to TYVASO® prior to the expiration of the patents-in-suit (Compl. ¶2, ¶22).
IV. Analysis of Infringement Allegations
The complaint provides a limited, narrative theory of infringement based on "information and belief," pending discovery of Defendant's confidential FDA application. It alleges that the manufacture and sale of the Proposed Generic Product will infringe the asserted patents. No probative visual evidence provided in complaint.
U.S. Patent No. 9,593,066 Infringement Allegations
| Claim Element (from Independent Claim 8) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A process of preparing a pharmaceutical product ... comprising alkylating a triol intermediate... | On information and belief, the active pharmaceutical ingredient (API) for the Proposed Generic Product is manufactured by a third party, Yonsung, using the claimed process. | ¶5, ¶36 | col. 8:46-50 |
| hydrolyzing the resulting compound to form treprostinil, | The complaint alleges that an intermediate in the manufacture of the Proposed Generic Product is covered by one or more claims of the patent. | ¶36 | col. 9:8-20 |
| forming a salt of treprostinil stable at ambient temperature, | The manufacturing process for the API allegedly includes the claimed salt formation and purification step. | ¶36 | col. 9:37-57 |
| preparing a pharmaceutical product from the treprostinil salt after storage... | Liquidia's submission of its 505(b)(2) application for a product to be made by the claimed process is alleged to be an act of infringement. | ¶38 | col. 18:49-61 |
U.S. Patent No. 9,604,901 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical batch consisting of treprostinil or a salt thereof and impurities resulting from (a) alkylating a benzindene triol... | The Proposed Generic Product is alleged to be a pharmaceutical batch that is made using the patented process, which includes alkylating a specific starting material. | ¶53 | col. 17:25-28 |
| (d) isolating the salt of treprostinil... | The complaint alleges on information and belief that the manufacturing process for the Proposed Generic Product uses the claimed purification step of isolating a treprostinil salt. | ¶53 | col. 17:34-36 |
| wherein the pharmaceutical batch contains at least 2.9 g of treprostinil or its salt. | The complaint alleges the Proposed Generic Product will be manufactured and sold in commercial batches that meet the claim limitations. | ¶9, ¶27 | col. 18:1-2 |
Identified Points of Contention
- Factual Questions: For the ’066 and ’901 patents, a central dispute will be factual: what specific chemical process does Liquidia's API supplier, Yonsung Fine Chemicals Co., actually use to manufacture treprostinil? The complaint's allegations are based on information and belief, and the infringement case will depend on evidence obtained during discovery.
- Scope Questions: For the ’793 patent, a key question is whether the alleged dose range of the accused product (26.5-212 mcgs) meets the claimed limitation of a "single event dose" of "from 15 micrograms to 90 micrograms." The allegation suggests that some intended doses may fall within the claimed range while others may fall outside of it, raising questions about the extent of any infringement.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for a full analysis of claim construction disputes. However, based on the technology and allegations, certain terms may become central to the case.
- The Term: "therapeutically effective single event dose" (from '793 Patent, Claim 1)
- Context and Importance: This term is critical for the ’793 patent as it defines the amount of drug administered in a single treatment session. The infringement analysis will turn on whether the alleged 26.5-212 mcg doses of the accused product constitute a "single event dose" as defined by the patent, particularly in light of the claim's explicit recitation of a "15 micrograms to 90 micrograms" range.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification states that treprostinil "can be administered in a few single inhalations using a compact inhalation device" (’793 Patent, col. 5:13-15), which a party might argue suggests flexibility beyond the specific numbers recited in the claim itself.
- Evidence for a Narrower Interpretation: Claim 1 explicitly recites that the dose "comprises from 15 micrograms to 90 micrograms" (’793 Patent, col. 18:25-27). Furthermore, the examples and figures describe specific doses within this range, such as 30, 45, and 60 µg, which may be used to argue that the claimed range is a strict, defining limit of the invention (’793 Patent, Example 1, FIG. 1).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon FDA approval, Liquidia will induce infringement by providing a product with labeling and instructions that encourage others (e.g., patients, physicians) to perform the patented methods of treatment (’793 patent) and by contracting with others to manufacture the infringing product (’066 and ’901 patents) (Compl. ¶47, ¶64, ¶80). It further alleges contributory infringement, stating that the accused product and its API have no substantial non-infringing uses (Compl. ¶48, ¶65, ¶81).
- Willful Infringement: Willfulness is alleged for all three patents. The complaint asserts that Liquidia was aware of the patents, as evidenced by its Paragraph IV certification letter, and "acted without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶40, ¶57, ¶73). The allegations are based on both pre-suit and anticipated post-suit knowledge.
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this case will likely depend on the answers to several central questions, framed for the court's determination.
- A primary issue will be one of evidentiary proof: What is the actual chemical process used to manufacture the treprostinil API for Liquidia's proposed product? The viability of the infringement claims concerning the '066 and '901 process and product-by-process patents hinges entirely on facts that will emerge from discovery regarding the accused manufacturing methods.
- A second key question will be one of claim scope: For the '793 method-of-use patent, does the accused product's alleged dosing regimen of 26.5-212 mcg per administration fall within the scope of a "single event dose" that "comprises from 15 micrograms to 90 micrograms," as required by the patent's independent claim?
- A dispositive question for the litigation as a whole will be patent validity: Given that post-complaint IPR proceedings resulted in the cancellation of all claims of the '793 patent and a majority of the claims of the '901 patent, a crucial issue will be whether any asserted claims survive the litigation. The outcome of these administrative challenges significantly narrows the scope of the dispute and raises substantial questions about the ultimate enforceability of the patents-in-suit.