DCT
2:25-cv-02785
Jazz Pharma Inc v. Almaject Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Jazz Pharmaceuticals, Inc. (Delaware) and Gentium S.r.l. (Italy)
- Defendant: Almaject, Inc. (Delaware), Alvogen, Inc. (Delaware), and Alvogen PB Research and Development LLC (Delaware)
- Plaintiff’s Counsel: Saul Ewing LLP
- Case Identification: 2:25-cv-02785, D.N.J., 04/16/2025
- Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendants maintain regular and established physical places of business in the district and purposefully conduct business there.
- Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's Defitelio® (defibrotide sodium) drug product constitutes an act of patent infringement.
- Technical Context: The technology concerns methods for determining the biological activity of defibrotide, a drug extracted from natural sources, to ensure standardized potency in formulations used to treat hepatic veno-occlusive disease.
- Key Procedural History: The dispute arises under the Hatch-Waxman Act. Plaintiff’s patents are listed in the FDA’s Orange Book for the drug Defitelio®. Defendants filed ANDA No. 216293 seeking to market a generic version prior to patent expiration, serving a Paragraph IV Certification that alleges the patents-in-suit are invalid and/or not infringed.
Case Timeline
| Date | Event |
|---|---|
| 2012-06-22 | Earliest Priority Date for ’043, ’328, and ’348 Patents |
| 2021-08-10 | ’043 Patent Issued |
| 2022-02-01 | ’328 Patent Issued |
| 2023-09-05 | ’348 Patent Issued |
| 2025-03-04 | Almaject Sent Paragraph IV Notice Letter (on or after this date) |
| 2025-04-16 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,085,043 - “Euglobulin-based Method for Determining the Biological Activity of Defibrotide”
The Invention Explained
- Problem Addressed: The patent describes the technical challenge of ensuring consistent biological activity for drugs like defibrotide, which are derived from natural sources and exhibit inherent batch-to-batch variability. Prior methods for assessing activity were described as having "considerable experimental complexity" and "unsatisfactory reproducibility and precision" (’043 Patent, col. 2:6-8).
- The Patented Solution: The invention provides a standardized in vitro enzymatic assay to measure defibrotide's biological activity. The method involves combining defibrotide with mammalian euglobulin, a blood fraction containing plasminogen. Defibrotide catalyzes the conversion of plasminogen to plasmin, which then reacts with a specific substrate to release a measurable, often chromogenic, product (’043 Patent, Abstract; col. 3:6-14). The rate of this product release is directly proportional to the concentration and biological activity of the defibrotide sample, as illustrated in the patent's Figure 1, which shows increased absorbance over time in a dose-dependent manner (’043 Patent, Fig. 1).
- Technical Importance: This standardized assay enables precise quantification of defibrotide's biological potency, allowing for reliable and reproducible dosing in medicinal preparations independent of variations from the raw material extraction process (’043 Patent, col. 2:41-49).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶40).
- Claim 1 of the ’043 Patent recites:
- A defibrotide formulation consisting of defibrotide, sodium citrate, and water for injection;
- Having a potency of 25 to 35 IU/mg;
- Having a concentration of at least 80 mg/mL; and
- Wherein the potency is determined by a specific method that involves bringing defibrotide into contact with mammalian euglobulin and a plasmin-specific substrate and measuring the resulting product formation over time.
U.S. Patent No. 11,236,328 - “Euglobulin-based Method for Determining the Biological Activity of Defibrotide”
The Invention Explained
- Problem Addressed: The ’328 Patent, sharing a common specification with the ’043 Patent, addresses the same technical problem of standardizing the biological activity of naturally-sourced defibrotide to ensure consistent therapeutic effect (’328 Patent, col. 1:45-53).
- The Patented Solution: The patent describes the same euglobulin-based enzymatic assay to determine defibrotide potency by measuring its effect on the rate of plasminogen-to-plasmin conversion (’328 Patent, Abstract; col. 3:8-22).
- Technical Importance: The method provides a validated, precise, and reproducible means to standardize the biological activity of defibrotide, which is critical for its use as a pharmaceutical product (’328 Patent, col. 2:43-51).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶50).
- Claim 1 of the ’328 Patent recites:
- A method of treating Veno-Occlusive Disease (VOD);
- Comprising administering a formulation consisting of defibrotide, sodium citrate, and water for injection;
- Wherein the formulation has a potency of 25 to 35 IU/mg and a concentration of at least 80 mg/mL; and
- Wherein the potency is determined by the same euglobulin-based assay method recited in the ’043 Patent.
U.S. Patent No. 11,746,348 - “Euglobulin-based Method for Determining the Biological Activity of Defibrotide”
Technology Synopsis
- Belonging to the same family as the ’043 and ’328 patents, the ’348 patent addresses the technical problem of ensuring batch-to-batch consistency for naturally-sourced defibrotide. It discloses an in vitro enzymatic assay where defibrotide’s biological activity is quantified by measuring its catalysis of plasminogen activation, enabling standardization of the drug’s potency (’348 Patent, Abstract; col. 1:43-2:12).
Asserted Claims
- The complaint asserts at least independent claim 1 (Compl. ¶60).
Accused Features
- The complaint alleges that Almaject’s submission of an ANDA for a generic defibrotide product, which is formulated for injection and intended for the treatment of VOD, infringes the ’348 patent (Compl. ¶¶35, 60-61).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Almaject's Proposed Product," a generic defibrotide sodium formulation in vials of 250 mg/2.5 mL, as described in ANDA No. 216293 (Compl. ¶35).
Functionality and Market Context
- The proposed product is a generic version of Plaintiff's FDA-approved drug, Defitelio®, and is intended for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), following hematopoietic stem-cell transplantation (Compl. ¶11, ¶35). The complaint alleges that Defendants seek FDA approval to manufacture, use, and sell this generic product in the United States prior to the expiration of the patents-in-suit (Compl. ¶¶35-36).
IV. Analysis of Infringement Allegations
11,085,043 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A defibrotide formulation consisting of defibrotide, sodium citrate, and water for injection... | Almaject's Proposed Product is described as "defibrotide sodium vials" intended for injection, which the complaint alleges meets the formulation requirements of the claim. | ¶35, ¶41 | col. 12:48-50 |
| ...having a potency of 25 to 35 IU/mg... | The complaint alleges that the product described in Almaject's ANDA satisfies the claimed potency range. | ¶41 | col. 12:50-51 |
| ...and a concentration of at least 80 mg/mL... | The proposed product is described as 250 mg in 2.5 mL, which corresponds to a concentration of 100 mg/mL. | ¶35 | col. 12:51-52 |
| ...wherein the defibrotide potency is determined by a method comprising the steps of: a) bringing into contact defibrotide, mammalian euglobulin and a substrate specific for plasmin... and b) measuring the amount of product formed... | The complaint alleges that the ANDA product meets the potency limitation, which is defined by this specific testing methodology. | ¶41 | col. 12:52-61 |
11,236,328 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating Veno-Occlusive Disease (VOD) comprising administering to a patient in need thereof a defibrotide formulation... | Defendants' proposed product is a generic version of Defitelio®, which is approved for treating VOD. The ANDA filing itself is the basis for alleging the claimed method will be practiced upon FDA approval. | ¶11, ¶35, ¶51, ¶54 | col. 12:44-47 |
| ...consisting of defibrotide, sodium citrate, and water for injection... | The proposed product is described as "defibrotide sodium vials" intended for injection, which the complaint alleges meets the formulation requirements. | ¶35, ¶51 | col. 12:47-49 |
| ...having a potency of 25 to 35 IU/mg, and a concentration of at least 80 mg/mL... | The complaint alleges the ANDA product satisfies the claimed potency and concentration limitations, with the concentration being 100 mg/mL (250 mg / 2.5 mL). | ¶35, ¶51 | col. 12:49-52 |
| ...wherein the defibrotide potency is determined by a method comprising the steps of [the recited assay]... | The complaint alleges that the ANDA product meets the potency limitation, which is defined by this specific testing methodology. | ¶51 | col. 12:52-62 |
Identified Points of Contention
- Scope Questions: A central issue may be whether the phrase "wherein the defibrotide potency is determined by a method" requires the accused infringer to actually practice the claimed assay. Defendants may argue that their product does not infringe if they use a different, non-infringing method to assess potency for their ANDA submission, even if the product itself possesses the claimed potency.
- Technical Questions: The complaint does not specify the exact method used by Defendants to determine the potency of their proposed product. A key factual question will be whether the testing methodology described in Almaject's ANDA falls within the scope of the steps recited in the asserted claims, including the use of "mammalian euglobulin" and a specific type of substrate.
V. Key Claim Terms for Construction
The Term: "potency... is determined by a method"
- Context and Importance: This phrase appears in the independent claims of all asserted patents and links the claimed formulation or treatment method to a specific measurement technique. Practitioners may focus on this term because its construction will likely decide whether infringement requires active practice of the patented assay by the defendant, or if it is sufficient that the accused product has the intrinsic properties that would yield the claimed potency if tested by that assay.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification's focus is on creating a product with a "defined biological activity" (’043 Patent, Abstract). Plaintiff may argue the claim language defines an objective, intrinsic property of the formulation (its potency), and the "determined by" language merely specifies how that property is to be measured for the purposes of establishing infringement, regardless of the method an ANDA filer actually uses.
- Evidence for a Narrower Interpretation: The claims use the active phrase "is determined by," which suggests an affirmative step. The patent's background criticizes prior art methods of determination, framing the patented method as a key part of the solution (’043 Patent, col. 2:1-10). A defendant could argue this context supports a narrower construction where the specific method must actually be practiced to meet the limitation.
The Term: "mammalian euglobulin" (’043 Patent, cl. 1) / "a biological composition comprising plasminogen" (’348 Patent, cl. 1)
- Context and Importance: This term defines the primary biological reagent in the patented assay. The infringement analysis may turn on whether the biological composition used in the defendant's potency test, as disclosed in its ANDA, meets this definition.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification states that while euglobulin fraction is the "enzymatic system of choice," the "use of other equivalent enzymatic systems, such as, for example, diluted plasma and serum...falls within the scope of the present invention" (’043 Patent, col. 4:9-17). This could support construing the term to cover other plasminogen-containing compositions beyond the strict definition of euglobulin.
- Evidence for a Narrower Interpretation: The claims of the ’043 and ’328 patents specifically recite "mammalian euglobulin." A defendant may argue that this clear language should not be broadened by specification language describing "equivalents," especially when a different patent in the same family (the ’348 patent) uses the broader term "a biological composition comprising plasminogen," suggesting the patentees knew how to claim more broadly when they intended to.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for all three patents-in-suit. Inducement is based on the allegation that, upon approval, Defendants will encourage infringement with knowledge of the patents, for example, by marketing the product and instructing physicians and patients on its use for the claimed method of treatment (Compl. ¶¶14-15, 44, 54, 64). Contributory infringement is based on the allegation that the proposed product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶¶45, 55, 65).
- Willful Infringement: The complaint does not use the term "willful," but it alleges that Defendants have knowledge of the patents-in-suit and requests an award of attorneys' fees under 35 U.S.C. § 285, alleging the case is "exceptional" (Compl. ¶¶44, 48, 54, 58, 64, 68).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim scope and proof: Does infringement of the "potency" limitation require evidence that the defendant actually performed the patented assay, or is it sufficient to show that the accused generic product inherently possesses the physical and biological characteristics that would satisfy the claimed potency range if measured by that assay?
- A second central question will be one of validity: Arising from the Defendants' Paragraph IV certification, a key issue for the court will be whether the claimed defibrotide formulations, defined by a specific potency range as determined by the novel assay, are anticipated by or would have been obvious in light of prior art defibrotide products that existed before the patents' priority date.
- An essential evidentiary question will be one of technical overlap: What specific methodology for determining potency is described in the confidential portions of Almaject's ANDA, and does that methodology meet the claim limitations requiring, for example, "mammalian euglobulin" and a "substrate specific for the plasmin"?