DCT
1:22-cv-00724
Galderma Laboratories v. Apotex Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Galderma Laboratories, L.P. (Texas) and TCD Royalty Sub LP ( Delaware)
- Defendant: Apotex Inc. (Canada) and Apotex Corp. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:22-cv-00724, D. Del., 06/02/2022
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Apotex Corp. is a Delaware corporation and Defendant Apotex Inc. conducts business in the state through its subsidiary and has previously consented to jurisdiction in the district.
- Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic 40 mg doxycycline capsule constitutes an act of infringement of two patents covering once-daily, low-dose tetracycline formulations.
- Technical Context: The technology relates to pharmaceutical formulations designed to provide the anti-inflammatory benefits of doxycycline for conditions like rosacea, while maintaining blood concentrations below the threshold for antibiotic activity, through a single daily dose.
- Key Procedural History: This is a Hatch-Waxman action initiated within 45 days of Plaintiffs' receipt of a Paragraph IV Notice Letter from Defendants, dated April 19, 2022. The patents-in-suit are listed in the FDA's "Orange Book" as covering the branded drug ORACEA®. Notably, U.S. Patent No. 8,206,740 survived an inter partes review (IPR) proceeding (IPR2013-00368), with the Patent Trial and Appeal Board confirming the patentability of asserted claims 1, 2, 5-15, and 19-22, a factor that may inform the patent's presumption of validity.
Case Timeline
| Date | Event |
|---|---|
| 2003-04-07 | Earliest Priority Date for ’532 and ’740 Patents |
| 2010-07-06 | U.S. Patent No. 7,749,532 Issues |
| 2012-06-26 | U.S. Patent No. 8,206,740 Issues |
| 2015-05-13 | Inter Partes Review Certificate Issues for ’740 Patent |
| 2022-04-19 | Defendants Send Paragraph IV Notice Letter to Plaintiffs |
| 2022-06-02 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,749,532 - "Once Daily Formulations of Tetracyclines," Issued July 6, 2010
The Invention Explained
- Problem Addressed: The patent describes a need for a doxycycline formulation that can be taken once per day for its anti-inflammatory properties without producing antibiotic effects ('532 Patent, col. 2:1-5). Conventional antibiotic doses can lead to undesirable side effects, such as the disruption of healthy intestinal flora and the development of antibiotic-resistant organisms, while twice-daily dosing regimens for lower-dose products may reduce patient compliance ('532 Patent, col. 2:5-17).
- The Patented Solution: The invention is a pharmaceutical composition that combines an immediate-release (IR) component and a delayed-release (DR) component of doxycycline into a single, once-daily dosage form ('532 Patent, col. 2:46-51). This dual-release mechanism is designed to achieve and maintain steady-state blood levels of the drug high enough for anti-collagenase activity but low enough to avoid antibacterial effects, specifically between approximately 0.1 µg/ml and 1.0 µg/ml ('532 Patent, col. 2:37-41).
- Technical Importance: The formulation aims to provide the therapeutic benefits of doxycycline for chronic inflammatory conditions while minimizing common side effects and improving patient convenience compared to multi-dose regimens ('532 Patent, col. 2:1-5).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶34).
- Independent Claim 1 requires:
- An oral pharmaceutical composition of doxycycline.
- Which provides steady-state blood levels between a minimum of 0.1 µg/ml and a maximum of 1.0 µg/ml with once-daily dosing.
- The composition "consisting of":
- An IR portion with "about 30 mg doxycycline."
- A DR portion with "about 10 mg doxycycline," where the DR portion is in the form of "pellets coated with at least one enteric polymer."
- One or more pharmaceutically acceptable excipients.
U.S. Patent No. 8,206,740 - "Once Daily Formulations of Tetracyclines," Issued June 26, 2012
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’532 patent, the ’740 patent addresses the same technical problem: the need for a once-daily, sub-antimicrobial dose of doxycycline for treating inflammatory conditions while avoiding antibiotic side effects and improving patient compliance (’740 Patent, col. 2:1-19).
- The Patented Solution: The invention proposes the same solution: a single dosage form containing both immediate-release and delayed-release portions of doxycycline to maintain a specific, narrow therapeutic window of the drug's blood concentration (’740 Patent, col. 2:46-51). The detailed description and figures are substantially identical to those in the ’532 patent.
- Technical Importance: The technical contribution is identical to that of the ’532 patent, focusing on enabling a specific and beneficial therapeutic regimen through a novel formulation design (’740 Patent, col. 2:11-19).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶34).
- Independent Claim 1 requires:
- An oral pharmaceutical composition of doxycycline.
- Which provides steady-state blood levels between a minimum of 0.1 µg/ml and a maximum of 1.0 µg/ml with once-daily dosing.
- The composition "consisting of":
- An IR portion "comprising 30 mg doxycycline."
- A DR portion "comprising 10 mg doxycycline."
- Optionally, one or more pharmaceutically acceptable excipients.
III. The Accused Instrumentality
- Product Identification: Defendants' Abbreviated New Drug Application (ANDA) No. 217170 for "Doxycycline Capsules 40 mg" ("Apotex's ANDA Product") (Compl. ¶11).
- Functionality and Market Context: The complaint alleges that the accused product is a generic version of Plaintiffs' ORACEA® (doxycycline, USP) 40 mg Capsules (Compl. ¶34). On information and belief, Plaintiffs allege that Defendants have submitted data to the FDA to establish bioequivalence between the accused product and ORACEA® (Compl. ¶34). The complaint is filed under 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA for the purpose of obtaining approval to market a drug claimed in a patent as an act of infringement (Compl. ¶35). The complaint does not contain specific details about the formulation of the accused product, noting that Defendants have not provided any portions of the ANDA (Compl. ¶32).
IV. Analysis of Infringement Allegations
The infringement theory is based on the allegation that the accused product is a generic version of ORACEA® and is bioequivalent to it, and therefore will necessarily meet the limitations of the asserted claims (Compl. ¶34). The complaint does not provide a claim chart or specific factual evidence regarding the accused product's composition. No probative visual evidence provided in complaint.
’532 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An oral pharmaceutical composition of doxycycline... | The accused product is identified as "Doxycycline Capsules 40 mg," which is an oral pharmaceutical composition. | ¶11, 34 | col. 11:63 |
| ...which at a once-daily dosage will give steady state blood levels of doxycycline of a minimum of 0.1 µg/ml and a maximum of 1.0 µg/ml... | It is alleged on information and belief that the accused product, being bioequivalent to ORACEA®, will produce the claimed pharmacokinetic profile upon once-daily administration. | ¶34 | col. 11:64-12:1 |
| ...the composition consisting of (i) an immediate release (IR) portion...wherein the drug consists of about 30 mg doxycycline... | Based on its status as a generic equivalent to 40 mg ORACEA®, the accused product is alleged to contain an immediate release portion of approximately 30 mg doxycycline. | ¶34 | col. 12:1-4 |
| ...(ii) a delayed release (DR) portion...wherein the drug consists of about 10 mg doxycycline, in which the DR portion is in the form of pellets coated with at least one enteric polymer... | Based on its status as a generic equivalent to 40 mg ORACEA®, the accused product is alleged to contain a delayed release portion of approximately 10 mg doxycycline as enteric coated pellets. | ¶34 | col. 12:4-7 |
’740 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An oral pharmaceutical composition of doxycycline... | The accused product is identified as "Doxycycline Capsules 40 mg," which is an oral pharmaceutical composition. | ¶11, 34 | col. 12:49 |
| ...which at a once-daily dosage will give steady state blood levels of doxycycline of a minimum of 0.1 µg/ml and a maximum of 1.0 µg/ml... | It is alleged on information and belief that the accused product, being bioequivalent to ORACEA®, will produce the claimed pharmacokinetic profile. | ¶34 | col. 12:50-53 |
| ...the composition consisting of (i) an immediate release (IR) portion comprising 30 mg doxycycline... | Based on its status as a generic equivalent to 40 mg ORACEA®, the accused product is alleged to contain an immediate release portion of 30 mg doxycycline. | ¶34 | col. 12:54-55 |
| ...(ii) a delayed release (DR) portion comprising 10 mg doxycycline... | Based on its status as a generic equivalent to 40 mg ORACEA®, the accused product is alleged to contain a delayed release portion of 10 mg doxycycline. | ¶34 | col. 12:56-57 |
- Identified Points of Contention:
- Evidentiary Question: The central dispute will be factual, hinging on the contents of Defendants' confidential ANDA. The primary question is whether the accused product's formulation contains the specific 30 mg IR / 10 mg DR split recited in the claims.
- Technical Question: A key technical question is whether the accused product, if administered as directed, will in fact produce the steady-state blood concentrations defined by the claims. While bioequivalence is alleged, the court may require evidence that the product's pharmacokinetic profile falls within the specific numerical ranges claimed.
- Scope Questions: For the ’532 patent, a potential dispute is whether the accused product's DR component, if one exists, is in the specific form of "pellets coated with at least one enteric polymer." A different DR technology could support a non-infringement argument. The corresponding claim in the ’740 patent is broader on this point and may be less susceptible to such a defense.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for analysis of specific claim construction disputes, as Defendants have not yet answered or provided the ANDA. However, based on the claim language, certain terms are likely to be central.
The Term: "about 30 mg doxycycline" / "about 10 mg doxycycline"
Context and Importance: These terms define the core quantitative split between the IR and DR components. The scope of "about" will be critical to determining literal infringement, as it addresses permissible manufacturing variances. Practitioners may focus on this term because infringement could turn on whether the accused product's dosage split, if not exactly 30/10, is close enough to be considered "about" those values.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discloses preferred IR:DR ratios of "about 70:30 to about 80:20," which for a 40 mg total dose would correspond to an IR dose of 28-32 mg and a DR dose of 8-12 mg, suggesting the patentee contemplated a range around the recited values (’532 Patent, col. 2:55-58).
- Evidence for a Narrower Interpretation: The claims themselves recite "about 30 mg" and "about 10 mg." Example 3 describes calculating a fill weight to deliver precisely 30 mg from the IR portion and 10 mg from the DR portion, which may support a narrower construction limited to minor processing tolerances (’532 Patent, col. 10:10-17).
The Term: "consisting of"
Context and Importance: This is a restrictive transition phrase in patent law, meaning the composition must include the listed elements and no others that materially alter its basic and novel properties. The analysis will depend on whether the accused product contains any additional, unrecited components that affect the formulation's release characteristics.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party arguing for a less restrictive view might point to the allowance of "pharmaceutically acceptable excipients" as showing that the presence of other conventional, inert ingredients was contemplated and does not violate the "consisting of" language.
- Evidence for a Narrower Interpretation: The term itself is strong evidence for a narrow scope. The presence of any unlisted active agent, or even an unlisted excipient that materially impacts the dissolution profile or bioavailability, could place the accused product outside the scope of the claim.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that should the ANDA be approved and the product launched, Defendants would induce infringement under 35 U.S.C. § 271(b) and contribute to infringement under § 271(c) (Compl. ¶37). The basis for inducement would presumably be the product's labeling and package insert, which would instruct physicians and patients to use the product in an infringing manner (i.e., once-daily dosing).
- Willful Infringement: Willfulness is alleged based on Defendants' pre-suit knowledge of the patents, as evidenced by their filing of a Paragraph IV certification (Compl. ¶40). Plaintiffs assert that Defendants "had no reasonable basis to believe that it did not infringe," and request a finding that the case is "exceptional," which could entitle them to enhanced damages and attorneys' fees (Compl. ¶40; Prayer for Relief ¶F).
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this case will likely depend on the answers to three central questions that emerge from the pleadings and patent documents:
A dispositive factual question will be one of composition: Does the formulation described in Defendants' confidential ANDA contain an immediate-release component of approximately 30 mg of doxycycline and a delayed-release component of approximately 10 mg, as required by the asserted claims?
A key infringement question will be one of structural correspondence, particularly for the ’532 patent: Assuming the 30/10 dosage split is present, does the accused product's delayed-release mechanism employ "pellets coated with at least one enteric polymer," or does it use a different technology that falls outside the literal claim scope?
A critical technical question will be one of pharmacokinetic performance: Will the accused product, upon once-daily administration, demonstrably produce the steady-state blood plasma concentrations specified in the claims (a minimum of 0.1 µg/ml and a maximum of 1.0 µg/ml)?