DCT
2:19-cv-09031
Eagle Pharma Inc v. Accord Healthcare Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Eagle Pharmaceuticals, Inc. (Delaware/New Jersey) and Chiesi USA, Inc. (Delaware/North Carolina)
- Defendant: Accord Healthcare, Inc. (North Carolina)
- Plaintiff’s Counsel: Saul Ewing Arnstein & Lehr LLP
- Case Identification: Eagle Pharmaceuticals, Inc. and Chiesi USA, Inc. v. Accord Healthcare, Inc., 2:19-cv-09031, D.N.J., 03/27/2019
- Venue Allegations: Venue is based on Defendant's alleged systematic and continuous business contacts with New Jersey, including being licensed by the state as a pharmaceutical manufacturer and deriving substantial revenue from product sales in the district.
- Core Dispute: Plaintiffs allege that Defendant’s filing of a New Drug Application to market a generic version of Plaintiffs' Argatroban Injection drug product constitutes an act of infringement of two patents covering alcohol-free formulations of the drug.
- Technical Context: The technology concerns pharmaceutical formulations of argatroban, an injectable anti-coagulant drug used for the treatment and prevention of thrombosis.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of New Drug Application (NDA) No. 212035 and its accompanying Paragraph IV Certification. The certification asserts that the patents-in-suit, which are listed in the FDA's Orange Book for Plaintiffs' argatroban product, are invalid, unenforceable, or will not be infringed by Defendant's proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2006-09-27 | Earliest Priority Date for '106 and '516 Patents |
| 2009-09-15 | U.S. Patent No. 7,589,106 ('106 Patent) Issue Date |
| 2010-03-30 | U.S. Patent No. 7,687,516 ('516 Patent) Issue Date |
| 2019-02-12 | Plaintiff Eagle received Defendant's Paragraph IV Notice |
| 2019-03-27 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,589,106 - “Alcohol Free Formulation of Argatroban,” Issued September 15, 2009
The Invention Explained
- Problem Addressed: The patent’s background section states that argatroban has poor solubility in water, which previously necessitated the use of ethanol and saccharides (like D-sorbitol) to create a stable, injectable formulation ('106 Patent, col. 1:32-49). The specification notes that the presence of ethanol is a drawback, particularly for certain patients, and the high concentration of the prior art product led to "substantial waste of material" after dilution ('106 Patent, col. 1:49-62).
- The Patented Solution: The invention is an aqueous formulation for argatroban that is "substantially free of ethanol" and "substantially free of a sugar alcohol" ('106 Patent, col. 11:18-21). The formulation achieves stability and solubility by using a specific combination of excipients, including the amino acid methionine and lactobionic acid, within an aqueous solution having a pH "in excess of 8.5" ('106 Patent, col. 11:2-21). The patent's Formula I provides a diagram of the argatroban chemical structure at the core of the formulation ('106 Patent, col. 3:1-18).
- Technical Importance: This technology provides for a ready-to-administer or concentrated injectable argatroban formulation that avoids the use of alcohol as a co-solvent, potentially reducing adverse patient reactions and drug waste ('106 Patent, col. 2:10-21).
Key Claims at a Glance
- The complaint asserts "one or more claims" of the patent; independent claim 1 is representative ('106 Patent, col. 11:2-21).
- The essential elements of claim 1 are: (1) a formulation of argatroban (or its salt) in an aqueous solution, comprising (2) methionine, (3) a non-amino acid pH adjusting agent, and (4) lactobionic acid, where the formulation is (5) substantially free of ethanol, (6) substantially free of a sugar alcohol, and (7) has a pH in excess of 8.5.
- The complaint reserves the right to assert other claims, including dependent claims (Compl. ¶25).
U.S. Patent No. 7,687,516 - “Alcohol Free Formulation of Argatroban,” Issued March 30, 2010
The Invention Explained
- Problem Addressed: The patent, which shares a common specification with the '106 Patent, identifies the same technical challenge: the poor water solubility of argatroban and the drawbacks of using ethanol and saccharides in prior injectable formulations ('516 Patent, col. 1:40-50).
- The Patented Solution: The '516 Patent also discloses an aqueous formulation of argatroban that is substantially free of alcohol and saccharides ('516 Patent, col. 2:55-62). The solution, as depicted in the patent's Formula I diagram, is achieved by solubilizing argatroban in an aqueous solution containing methionine, lactobionic acid, and an optional buffer, with a final pH in excess of 8.5 ('516 Patent, Abstract; col. 11:30-44).
- Technical Importance: The invention enables an alternative stable, injectable formulation of argatroban that circumvents the need for potentially undesirable excipients like ethanol ('516 Patent, col. 2:5-14).
Key Claims at a Glance
- The complaint asserts "one or more claims" of the patent; independent claim 1 is representative ('516 Patent, col. 11:30-44).
- The essential elements of claim 1 are: (1) an aqueous formulation of argatroban (or its salt) solubilized at a concentration greater than in water alone, comprising (2) methionine, (3) lactobionic acid (or its salts/mixtures), and (4) an optional buffer, where the formulation (5) has a pH in excess of 8.5.
- The complaint reserves the right to assert other claims (Compl. ¶34).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Accord's Proposed Product," which is a generic Argatroban Injection drug product described in Defendant's NDA No. 212035 (Compl. ¶1, ¶17).
Functionality and Market Context
- The product is an injectable medication intended for the treatment of thrombosis (Compl. ¶7). As a generic drug submitted for FDA approval via an NDA, it is intended to be a therapeutic equivalent to Plaintiffs' approved Argatroban Injection product (Compl. ¶1, ¶9).
- The complaint does not provide specific details regarding the formulation of Accord's Proposed Product, as this information is contained within the confidential NDA. The infringement allegations are based on the statutory act of filing the NDA for a product that, if marketed, would allegedly infringe the patents-in-suit (Compl. ¶25, ¶34).
IV. Analysis of Infringement Allegations
The complaint makes general allegations of infringement as is typical in Hatch-Waxman cases filed prior to discovery. The central theory is that Accord's Proposed Product, as described in its NDA, will meet all limitations of the asserted claims.
'106 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A...formulation...solubilized in an aqueous solution, said formulation comprising (a) argatroban of formula I or a pharmaceutically acceptable salt thereof | The complaint alleges Accord's Proposed Product is a formulation of argatroban in an aqueous solution. | ¶25 | col. 11:2-5 |
| (b) methionine... | The complaint alleges Accord's Proposed Product contains methionine. | ¶25 | col. 11:6-8 |
| (c) a member selected from the group consisting of...non-amino acid pH adjusting...acids, ...bases, or salts thereof... | The complaint alleges Accord's Proposed Product contains a pH adjusting agent. | ¶25 | col. 11:9-14 |
| (d) a member selected from the group consisting of lactobionic acid... | The complaint alleges Accord's Proposed Product contains lactobionic acid. | ¶25 | col. 11:15-17 |
| which formulation is substantially free of ethanol and substantially free of a sugar alcohol | The complaint alleges Accord's Proposed Product is substantially free of ethanol and sugar alcohol. | ¶25 | col. 11:18-20 |
| and has a pH in excess of 8.5. | The complaint alleges Accord's Proposed Product has a pH in excess of 8.5. | ¶25 | col. 11:20-21 |
'516 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A...formulation of argatroban...solubilized in aqueous solution at a concentration greater than that of argatroban in water alone, comprising (a) argatroban... | The complaint alleges Accord's Proposed Product is an argatroban formulation solubilized in an aqueous solution. | ¶34 | col. 11:30-38 |
| (b) methionine; | The complaint alleges Accord's Proposed Product contains methionine. | ¶34 | col. 11:39 |
| (c) lactobionic acid, pharmaceutically acceptable salts, and mixtures thereof; and | The complaint alleges Accord's Proposed Product contains lactobionic acid. | ¶34 | col. 11:40-42 |
| (d) an optional buffer; | The complaint alleges Accord's Proposed Product contains a buffer. | ¶34 | col. 11:43 |
| wherein the formulation has a pH in excess of 8.5 | The complaint alleges Accord's Proposed Product has a pH in excess of 8.5. | ¶34 | col. 11:44 |
Identified Points of Contention
- Scope Questions: A potential dispute may arise over the meaning of "substantially free of ethanol" and "substantially free of a sugar alcohol." The question will be whether any trace amounts of these substances in Accord's product fall within the scope of this limitation as defined by the patents.
- Technical Questions: A primary factual question for discovery will be whether the formulation detailed in Accord's confidential NDA actually contains every element of the asserted claims—specifically, the combination of argatroban, methionine, and lactobionic acid in an aqueous solution with a pH above 8.5.
V. Key Claim Terms for Construction
- The Term: "substantially free of ethanol"
- Context and Importance: This term is central to the patents' assertion of novelty over prior art formulations that required ethanol as a co-solvent. The construction of "substantially" will be critical to the infringement analysis if the accused product contains any amount of ethanol.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue the term means free from any functionally significant amount of ethanol added as a primary solubilizing agent, as distinct from trace impurities.
- Evidence for a Narrower Interpretation: The specification provides explicit quantitative guidance, defining "substantial free" of a lower alcohol as "less than about 5% v/v, preferably less than about 2.5%, more preferably less than about 1%, more preferably less than about 0.5% v/v" ('106 Patent, col. 6:58-62). This language provides strong intrinsic evidence for a numerically bounded definition.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for both patents. The inducement allegation is based on the claim that Defendant, with knowledge of the patents, will encourage direct infringement by end-users through its product labeling and instructions (Compl. ¶28, ¶37). The contributory infringement allegation is based on the claim that Defendant's product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶29, ¶38).
- Willful Infringement: While not pleaded as a separate count, the complaint alleges the necessary elements for willfulness by asserting that Defendant possessed knowledge of the patents and infringement, giving rise to claims for an "exceptional case" and attorneys' fees under 35 U.S.C. § 285 (Compl. ¶32, ¶41). This knowledge is evidenced by Defendant's Paragraph IV certification and notice letter (Compl. ¶22, ¶23).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of claim construction: How will the court define the scope of the term "substantially free," particularly in relation to ethanol and sugar alcohols? The specification's explicit numerical guidance may heavily influence this determination, which could be dispositive if the accused product contains trace amounts of these compounds.
- A key evidentiary question will be one of chemical composition: Will discovery confirm that the formulation described in Defendant's confidential NDA practices every element of the asserted claims? The outcome will depend on whether Accord's product contains the specific combination of methionine and lactobionic acid in an aqueous solution at the claimed pH.
- The litigation will likely focus on patent validity: In Hatch-Waxman litigation where a generic product is designed to be a therapeutic equivalent of the branded drug, the defendant's primary defense often shifts from non-infringement to invalidity. The assertion in Defendant's Paragraph IV letter that the patents are invalid or unenforceable suggests that challenges to patentability (e.g., obviousness) will be a critical battleground (Compl. ¶22).