DCT
1:22-cv-02868
Ingenus Pharma LLC v. Nexus Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Ingenus Pharmaceuticals, LLC (Florida) and Leiutis Pharmaceuticals LLP (India)
- Defendant: Nexus Pharmaceuticals, Inc. (Illinois)
- Plaintiff’s Counsel: Green, Griffith & Associates LLP; Sughrue Mion PLLC
- Case Identification: 1:22-cv-02868, N.D. Ill., 06/01/2022
- Venue Allegations: Venue is alleged to be proper in the Northern District of Illinois because the Defendant is incorporated in Illinois, maintains its principal place of business in the district, and stated in its regulatory filings to the FDA that "Venue is appropriate in the Northern District of Illinois."
- Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic cyclophosphamide injectable solution constitutes an act of infringement of a patent covering a stable, ready-to-use liquid formulation of the drug.
- Technical Context: The dispute concerns formulations for cyclophosphamide, an injectable chemotherapy drug, with the patent focused on creating a liquid version that is stable and does not require reconstitution before use, unlike prior powder-based versions.
- Key Procedural History: This case was initiated under the Hatch-Waxman Act following Defendant's submission of an ANDA with a Paragraph IV certification, asserting that its proposed generic product would not infringe or that the patent-in-suit is invalid. Plaintiffs filed this suit within the 45-day statutory window after receiving Defendant's notice letter, triggering an automatic 30-month stay on the FDA’s approval of the generic product.
Case Timeline
| Date | Event |
|---|---|
| 2015-02-16 | '952 Patent Priority Date |
| 2020-07-30 | FDA Approval of Plaintiffs' NDA No. 212501 |
| 2021-05-04 | '952 Patent Issue Date |
| 2021-11-19 | FDA Approval of Plaintiffs' Supplemental NDA |
| 2022-04-21 | Defendant sends Paragraph IV Notice Letter |
| 2022-06-01 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,993,952 - "Stable Ready to Use Cyclophosphamide Liquid Formulations"
- Patent Identification: U.S. Patent No. 10,993,952, "Stable Ready to Use Cyclophosphamide Liquid Formulations," issued May 4, 2021.
The Invention Explained
- Problem Addressed: The patent’s background section describes that prior formulations of the drug cyclophosphamide were typically supplied as a lyophilized (dry) powder that required reconstitution with a liquid diluent before administration. This process was described as decreasing the "ease of administration," and the reconstituted solutions could only be stored for a fixed period. The patent also notes that the drug is "susceptible to hydrolysis," which can lead to the formation of impurities and reduced stability. (’952 Patent, col. 2:37-43, 2:60-64).
- The Patented Solution: The invention is a "stable ready to use, liquid parenteral formulation" that eliminates the need for reconstitution. It achieves stability by dissolving cyclophosphamide in a specific solvent system that includes particular ratios of ethanol, polyethylene glycol, and propylene glycol, and may include an antioxidant. This formulation is designed to control the formation of hydrolytic degradation impurities. (’952 Patent, col. 2:40-48, Abstract).
- Technical Importance: The invention provides a formulation that can improve safety and efficiency in clinical settings by providing a pre-mixed, stable injectable solution, thereby reducing preparation steps and potential for contamination or dosing errors. (’952 Patent, col. 2:60-64).
Key Claims at a Glance
- The complaint alleges infringement of "one or more claims" of the ’952 Patent (Compl. ¶35). The independent claims are Claims 1 and 4.
- Independent Claim 1: A stable liquid parenteral formulation comprising:
- Cyclophosphamide at about 12% to about 23% by total formulation weight;
- Ethanol at about 70% to about 75% by total formulation weight;
- Both polyethylene glycol and propylene glycol, with a mass ratio between them from approx. 1.0:1.0 to 2.0:1.0;
- Polyethylene glycol at about 3.4% to about 8.8% by total formulation weight;
- Propylene glycol at about 3.4% to about 4.4% by total formulation weight; and
- A stability requirement wherein specific impurities are less than 0.5% after 7 days of accelerated storage.
- Independent Claim 4: A stable liquid parenteral formulation comprising:
- Cyclophosphamide at about 23% by total formulation weight;
- Ethanol at about 70% by total formulation weight;
- Both polyethylene glycol and propylene glycol, with a mass ratio of about 1.0:1.0;
- Polyethylene glycol at about 3.4% to about 8.8% by total formulation weight;
- Propylene glycol at about 3.4% to about 4.4% by total formulation weight; and
- Monothioglycerol (an antioxidant) at about 0.02% by total formulation weight.
- The complaint does not explicitly reserve the right to assert dependent claims, but the general allegation of infringing "one or more claims" leaves this possibility open.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendant’s proposed generic "cyclophosphamide solution for intravenous injection, 500 mg/2.5 mL and 1 mg/5 mL (200 mg/mL)," as described in Abbreviated New Drug Application (ANDA) No. 216783 ("Nexus's ANDA Product"). (Compl. ¶9).
Functionality and Market Context
- The complaint alleges the ANDA Product is a "purported generic version" of Plaintiffs’ own FDA-approved Cyclophosphamide Injection. (Compl. ¶24). It is intended for the same medical indication: the treatment of various malignant diseases. (Compl. ¶28). The complaint alleges that Defendant intends to sell the ANDA Product in the U.S. upon approval, which would "displace sales of Plaintiffs' Cyclophosphamide Injection." (Compl. ¶13). The act of infringement alleged is the submission of the ANDA itself, which seeks approval to market a product whose formulation allegedly falls within the scope of the ’952 patent's claims. (Compl. ¶37).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges that the ANDA Product infringes but does not provide a detailed, element-by-element breakdown of its infringement theory. The following tables summarize the infringement allegations for the independent claims based on the complaint's general assertion that the ANDA Product meets the claim limitations.
'952 Patent Infringement Allegations (Claim 1)
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| i) cyclophosphamide in a concentration of about 12% to about 23% based on total formulation weight; | The formulation described in ANDA No. 216783, which allegedly contains cyclophosphamide within the claimed concentration range. | ¶35 | col. 8:21-23 |
| ii) an ethanol content of about 70% to about 75% based on total formulation weight; | The ANDA Product formulation allegedly contains ethanol within the claimed concentration range. | ¶35 | col. 8:24-26 |
| iii) both polyethylene glycol and propylene glycol, wherein a polyethylene glycol to propylene glycol mass ratio is between approximately 1.0:1.0 to approximately 2.0:1.0; | The ANDA Product formulation allegedly contains both polyethylene glycol and propylene glycol within the claimed mass ratio. | ¶35 | col. 8:27-30 |
| iv) about 3.4% to about 8.8% based on total formulation weight of polyethylene glycol | The ANDA Product formulation allegedly contains polyethylene glycol within the claimed concentration range. | ¶35 | col. 8:31-33 |
| v) about 3.4% to about 4.4% based on total formulation weight of propylene glycol | The ANDA Product formulation allegedly contains propylene glycol within the claimed concentration range. | ¶35 | col. 8:34-36 |
| vi) wherein, after storage for 7 days at 40° C./75% RH, decomposition to form any of the following impurities is less than 0.5%... | The ANDA Product is alleged to be a stable formulation that meets this functional stability requirement. | ¶35 | col. 8:37-45 |
'952 Patent Infringement Allegations (Claim 4)
| Claim Element (from Independent Claim 4) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| i. cyclophosphamide in a concentration of about 23% based on total formulation weight | The formulation described in ANDA No. 216783, which allegedly contains cyclophosphamide at the claimed concentration. | ¶35 | col. 8:49-51 |
| ii. an ethanol content of about 70% based on total formulation weight; | The ANDA Product formulation allegedly contains ethanol at the claimed concentration. | ¶35 | col. 8:52-53 |
| iii. both polyethylene glycol and propylene glycol, wherein a polyethylene glycol to propylene glycol mass ratio is about 1.0:1.0; | The ANDA Product formulation allegedly contains both excipients at the claimed mass ratio. | ¶35 | col. 8:54-57 |
| vi. about 0.02% based on total formulation weight of monothioglycerol. | The ANDA Product formulation allegedly contains the antioxidant monothioglycerol at the claimed concentration. | ¶35 | col. 8:64-66 |
- Identified Points of Contention:
- Technical Questions: The central technical question is whether the precise formulation disclosed in Defendant's confidential ANDA filing meets each of the specific concentration ranges and component ratios recited in the asserted claims. The complaint does not present this evidence, alleging infringement "on information and belief." (Compl. ¶28). A further technical question is whether the ANDA product meets the functional stability limitation of Claim 1, which requires specific test results.
- Scope Questions: The interpretation of the term "about" will be critical for every numerical limitation in the claims. The infringement analysis will depend on whether the court construes "about" narrowly (e.g., limited to rounding) or more broadly to encompass a range of equivalents, which may determine whether Defendant's formulation falls within the literal scope of the claims.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for a deep analysis of claim construction disputes. However, based on the patent's claims, certain terms are likely to be central.
The Term: "about"
Context and Importance: This term modifies every concentration and ratio limitation in the independent claims. Its construction will directly determine the literal boundaries of the claims. Whether the Defendant's formulation infringes will likely hinge on the scope afforded to "about". Practitioners may focus on this term because even small differences in formulation between the patented product and the generic version could be dispositive if the term is construed narrowly.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not explicitly define "about". A party arguing for a broader scope may contend it should be given its ordinary meaning in the art of pharmaceutical formulation, which generally implies a degree of acceptable variance.
- Evidence for a Narrower Interpretation: The use of "approximately" in Claim 1, element (iii), in addition to "about" in other elements, could suggest the terms have different meanings or that the patentee was deliberate in its word choice. A party arguing for a narrower scope may point to the specific values in the patent's examples (e.g., Example 1) as context for the intended precision. (’952 Patent, col. 3-4; col. 8:28).
The Term: "stable"
Context and Importance: This term appears in the preamble of the claims and describes the overall purpose of the invention. Its definition is critical because the dispute is over whether the accused product is an equivalent, stable formulation.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The background describes stability in general terms, such as overcoming the disadvantages of prior art formulations that required reconstitution and had limited storage time. (’952 Patent, col. 2:60-64).
- Evidence for a Narrower Interpretation: Claim 1, element (vi) provides a specific, functional definition of stability by requiring that certain impurities remain below 0.5% after accelerated storage. A party could argue that this limitation defines the term "stable" for the entire patent, requiring any infringing product to meet this specific performance metric. (’952 Patent, col. 8:37-45).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon FDA approval, Defendant will actively induce infringement by encouraging the use of its ANDA Product in a manner that infringes. (Compl. ¶39). It also alleges contributory infringement, stating that the ANDA Product is "especially made or especially adapted for a use that infringes" and has "no substantial noninfringing uses." (Compl. ¶40).
- Willful Infringement: The complaint does not use the term "willful" but alleges Defendant had "actual and constructive notice of the '952 patent prior to filing" its ANDA and "has no reasonable basis for asserting" non-infringement or invalidity. (Compl. ¶41). This is used to support a claim that the case is "exceptional" under 35 U.S.C. § 285, which would entitle Plaintiffs to attorneys' fees. (Compl. ¶42).
VII. Analyst’s Conclusion: Key Questions for the Case
- An evidentiary question will be paramount: What are the exact ingredients and concentrations detailed in Nexus's confidential ANDA filing? The outcome of the literal infringement analysis depends entirely on this information, which will only become available through discovery.
- A core issue will be one of claim construction: How broadly will the court interpret the term "about" as it applies to the concentration and ratio limitations in the claims? A narrow construction could allow for a non-infringement defense based on minor formulation differences, while a broader construction would make such a defense more difficult.
- A key factual and functional question will be: Can Plaintiffs demonstrate that Defendant’s product meets the stability requirements of Claim 1? This requires not just a comparison of ingredients but empirical evidence showing that the accused formulation produces less than 0.5% of specific impurities under accelerated storage conditions.