DCT
1:24-cv-00988
Takeda Pharma USA Inc v. Colomba Therap Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Takeda Pharmaceuticals U.S.A., Inc. (Delaware)
- Defendant: Colomba Therapeutics, Inc. (Delaware) and Pharmascience Inc. (Canada)
- Plaintiff’s Counsel: Faegre Drinker Biddle & Reath LLP
- Case Identification: 1:24-cv-00988, D. Del., 09/10/2024
- Venue Allegations: Venue is asserted based on Defendant Colomba's incorporation in Delaware and allegations that both Defendants conduct substantial and continuous business in the district.
- Core Dispute: Plaintiff alleges that Defendants' submission of a New Drug Application (NDA) for their colchicine-based product, Myinfla®, constitutes an act of infringement of a patent covering methods for safely co-administering colchicine with other specific drugs.
- Technical Context: The technology concerns pharmaceutical dosing methods designed to mitigate the risk of potentially fatal toxicity when colchicine, a drug for gout, is taken concurrently with other drugs that inhibit its metabolism.
- Key Procedural History: This action was filed under the Hatch-Waxman Act, triggered by Defendants' submission of NDA No. 216469 to the FDA with a Paragraph IV certification. This certification asserts that U.S. Patent No. 7,964,648, which is listed in the FDA's Orange Book for Plaintiff's product Colcrys®, is invalid, unenforceable, or will not be infringed by the commercialization of Defendants' proposed product.
Case Timeline
| Date | Event |
|---|---|
| 2009-01-14 | '648 Patent Priority Date |
| 2009 | First FDA approval of Colcrys® |
| 2011-06-21 | '648 Patent Issue Date |
| 2023-12-15 | Defendants' NDA filing contains a Paragraph IV certification |
| 2024-09-10 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,964,648 - "Methods for Concomitant Administration of Colchicine and a Second Active Agent"
- Patent Identification: U.S. Patent No. 7,964,648, "Methods for Concomitant Administration of Colchicine and a Second Active Agent," issued June 21, 2011.
The Invention Explained
- Problem Addressed: The patent’s background section explains that colchicine has a "narrow therapeutic index," making the margin between an effective dose and a toxic dose dangerously small. Co-administration of colchicine with drugs that inhibit certain metabolic pathways (specifically involving CYP3A4 and P-gp) can significantly increase colchicine levels in the body, which has led to "serious morbid complications and, in some cases, death" (’648 Patent, col. 2:36-46).
- The Patented Solution: The invention provides methods for safely administering colchicine to patients who are also taking a second drug known to cause such interactions, such as ketoconazole. The solution involves administering an "adjusted daily dosage amount" of colchicine that is a specific, reduced fraction of the "intended" (i.e., standard) dose, thereby preventing the drug's concentration from reaching toxic levels (’648 Patent, Abstract; col. 11:46-54).
- Technical Importance: The patented method provided a quantifiable, data-driven approach to managing a known, life-threatening drug-drug interaction, thereby improving the safety profile for a widely prescribed medication (’648 Patent, col. 2:41-45).
Key Claims at a Glance
- The complaint asserts infringement of Claim 1 of the ’648 Patent (Compl. ¶22).
- The essential elements of independent Claim 1 are:
- A method of treating a patient with colchicine, comprising
- orally administering an adjusted daily dosage amount of colchicine to the patient who is receiving concomitant administration of ketoconazole,
- wherein the adjusted daily dosage amount of colchicine is 25% to 50% of an intended daily dosage amount of colchicine, and
- wherein the intended daily dosage amount of colchicine is a dosage amount suitable for the patient if the patient were not receiving concomitant ketoconazole.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Colomba's NDA Product," identified as Myinfla®, which is an oral colchicine drug product for which Defendants seek FDA approval (Compl. ¶¶1, 24).
Functionality and Market Context
- The infringement allegation centers on the proposed method of use for Myinfla®, as will be described in its FDA-approved label (Compl. ¶¶55-56). The complaint alleges that this label will instruct physicians and patients on how to administer Myinfla®, including instructions to adjust the dosage for patients who are concomitantly taking CYP3A4 inhibitors (a class of drugs that includes ketoconazole) to reduce the risk of colchicine toxicity (Compl. ¶¶54, 56). The complaint further alleges that Colomba's proposed label relied on published literature describing dose adjustment studies for Colcrys®, Plaintiff's own colchicine product (Compl. ¶39).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’648 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating a patient with colchicine, comprising orally administering an adjusted daily dosage amount of colchicine... | The proposed label for Myinfla®, an oral colchicine drug product, allegedly instructs physicians on how to administer the drug, including how to adjust or reduce the dose or dose frequency. | ¶56 | col. 7:20-24 |
| ...to the patient who is receiving concomitant administration of ketoconazole, | The proposed label allegedly instructs physicians on administering Myinfla® to patients who are "concomitantly receiving CYP3A4 inhibitors and/or P-gp inhibitors (e.g., ketoconazole)." | ¶56 | col. 28:44-49 |
| wherein the adjusted daily dosage amount of colchicine is 25% to 50% of an intended daily dosage amount of colchicine, and | The complaint alleges that Defendants are aware of studies (the Colcrys® DDI studies) that advise a 50% dose reduction when co-administered with ketoconazole, and that Colomba's label relied on this literature. The label allegedly instructs a dose reduction to avoid toxicity. | ¶19, ¶39, ¶56 | col. 22:41-43 |
| wherein the intended daily dosage amount of colchicine is a dosage amount suitable for the patient if the patient were not receiving concomitant ketoconazole. | The complaint alleges the existence of a standard-of-care dose (the "intended" dose) which is reduced when co-administered with certain inhibitors. The infringement theory relies on the instructions in the proposed label leading to a reduction from this standard, un-adjusted dose. | ¶18, ¶56 | col. 11:48-51 |
- Identified Points of Contention:
- Scope Questions: A primary issue is whether the general cautionary language allegedly in the proposed label—stating a dose "may need to be reduced or interrupted" (Compl. ¶54)—is specific enough to meet the quantitative "25% to 50%" limitation of Claim 1. The dispute may focus on whether such general instructions can be considered to direct infringement of a claim requiring a specific numerical range.
- Technical Questions: A key evidentiary question will be what Colomba’s proposed label actually instructs. Does it explicitly direct a dose reduction within the 25% to 50% range for patients on ketoconazole, or does it merely provide a general warning about potential interactions? The case may turn on whether Plaintiff can demonstrate that the label, by referencing external studies or otherwise, necessarily leads a physician to perform the patented method.
V. Key Claim Terms for Construction
The Term: "adjusted daily dosage amount"
- Context and Importance: This term is at the heart of the invention and the infringement allegation. The dispute will center on whether the dosage instructions on the Myinfla® label describe an "adjusted daily dosage amount" as claimed. Practitioners may focus on this term because its construction will determine whether a general instruction to "reduce the dose" is sufficient for infringement, or if a specific, calculated reduction is required.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification refers to this as a "reduced or modified daily dosage amount" determined from experiments, which could suggest some flexibility (’648 Patent, col. 11:51-54).
- Evidence for a Narrower Interpretation: Claim 1 itself limits the term to a specific range (25% to 50% of an intended dose). Furthermore, the patent provides highly specific examples of dose adjustments in its tables (e.g., reducing a dose from 0.6 mg twice daily to 0.6 mg once daily), which may be used to argue the term requires a precise, quantitative modification, not just a vague reduction (’648 Patent, col. 11:61-64; col. 12, Table).
The Term: "intended daily dosage amount"
- Context and Importance: This term establishes the baseline against which infringement is measured. To prove infringement, Plaintiff must establish what this "intended" amount is for a given patient, then show that the "adjusted" amount falls within the claimed percentage of it.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim itself provides a functional definition: "a dosage amount suitable for the patient if the patient were not receiving concomitant ketoconazole" (’648 Patent, col. 22:44-47). This language could be argued to encompass any standard, clinically appropriate dose.
- Evidence for a Narrower Interpretation: The patent specification provides tables listing specific "Original Intended Dose" regimens (e.g., "1.2 mg (2 tablets) at the first sign of the flare followed by 0.6 mg (1 tablet) one hour later") (’648 Patent, col. 12, Table). Defendants may argue that the term is implicitly limited to these established, standard-of-care dosages described in the patent.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement, stating that Defendants' proposed label will "instruct, encourage, recommend, and promote direct infringement" by physicians and patients (Compl. ¶62). The factual basis is the allegation that the label's instructions regarding dose adjustments will cause medical professionals to administer Myinfla® in a manner that directly infringes the ’648 Patent (Compl. ¶¶56, 70). The complaint also pleads contributory infringement (Compl. ¶¶67, 73).
- Willful Infringement: Willfulness is alleged based on Defendants having "acted with full knowledge of the '648' patent," with such knowledge being evidenced by their filing of a Paragraph IV certification that was required to, and did, specifically identify the patent-in-suit (Compl. ¶74).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary sufficiency: Does the specific text of Colomba's proposed Myinfla® label directly instruct or necessarily encourage physicians to reduce the colchicine dosage by the specific "25% to 50%" required by Claim 1 when co-administered with ketoconazole? The outcome may depend on whether the label's alleged reliance on external studies is enough to meet this claim limitation, even if the label's own text is more general.
- The case will also turn on a question of claim scope: Will the court construe the term "adjusted daily dosage amount" to require a specific, numerically-defined dose reduction as exemplified in the patent, or will it adopt a more flexible interpretation that could be met by a general instruction to "reduce or interrupt" the dose? The answer will define the boundary between non-infringing cautionary language and infringing instruction.