DCT
1:24-cv-00152
AbbVie Inc v. Prinston Pharmaceutical Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: AbbVie Inc. (Delaware)
- Defendant: Prinston Pharmaceutical Inc., Zhejiang Huahai Pharmaceutical Co., Ltd., and Solco Healthcare US, LLC (Delaware, People's Republic of China, and Delaware, respectively)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:24-cv-00152, D. Del., 02/05/2024
- Venue Allegations: Venue is alleged to be proper as Defendants Prinston Pharmaceutical and Solco Healthcare are incorporated in Delaware, and Defendant Zhejiang Huahai may be sued in any judicial district as a foreign entity.
- Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's ORILISSA® product constitutes an act of infringement of two patents covering methods of administering the drug.
- Technical Context: The case involves elagolix, a gonadotropin-releasing hormone (GnRH) receptor antagonist used to manage pain associated with endometriosis and other gynecological conditions by reducing estrogen levels.
- Key Procedural History: The complaint notes this action is the latest in a series of suits brought by AbbVie against the same Defendants concerning the same ANDA. Three prior suits asserting different patents were previously filed and consolidated in the District of Delaware, and those actions remain pending.
Case Timeline
| Date | Event |
|---|---|
| 2018-04-19 | Earliest Priority Date for ’854 Patent |
| 2018-07-23 | ORILISSA® (NDA No. 210450) approved by FDA |
| 2020-03-05 | Earliest Priority Date for ’845 Patent |
| 2022-09-13 | Prinston sends First Notice of Paragraph IV Certification |
| 2022-10-27 | AbbVie files "First Suit" against Prinston |
| 2023-03-14 | Prinston sends Second Notice of Paragraph IV Certification |
| 2023-04-20 | Prinston sends Third Notice of Paragraph IV Certification |
| 2023-04-28 | AbbVie files "Second Suit" against Prinston |
| 2023-06-02 | AbbVie files "Third Suit" against Prinston |
| 2023-07-04 | U.S. Patent No. 11,690,845 issues |
| 2023-07-04 | U.S. Patent No. 11,690,854 issues |
| 2023-08-16 | First, Second, and Third Suits are consolidated |
| 2024-02-05 | Current Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,690,845 - Methods of Administering Elagolix
Issued July 4, 2023
The Invention Explained
- Problem Addressed: The patent addresses the potential for drug-drug interactions between elagolix and bupropion, an antidepressant (’845 Patent, col. 1:21-34). Bupropion is metabolized by the enzyme CYP2B6, and the patent notes the potential for other drugs that inhibit or induce this enzyme to alter bupropion's plasma concentration, which may be linked to adverse events (’845 Patent, col. 1:28-36).
- The Patented Solution: The patent claims specific methods for co-administering elagolix and bupropion. The invention describes that while in vitro studies suggested elagolix might decrease bupropion exposure, clinical studies surprisingly showed an increase in the maximum concentration (Cmax) of bupropion and its metabolite (’845 Patent, col. 8:50-59). The claims cover a method of co-administration that results in specific, defined pharmacokinetic (PK) ratios for bupropion and its metabolite, hydroxybupropion (’845 Patent, col. 2:45-65).
- Technical Importance: The invention provides specific dosing regimens intended to manage drug interactions, potentially allowing for the safe and effective co-prescription of elagolix and bupropion.
Key Claims at a Glance
- The complaint asserts at least one claim of the '845 Patent (Compl. ¶67). Independent claim 1 is representative:
- A method for treating a gynecological disorder in a patient in need thereof, comprising orally administering to the patient sodium 4-({(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-4-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl]-1-phenylethyl}amino)butanoate (“elagolix sodium”),
- wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily,
- wherein the patient receives a once daily dose of 150 mg of bupropion, and
- wherein a specific set of four pharmacokinetic parameter ratios for bupropion and hydroxybupropion are achieved.
- The complaint reserves the right to assert infringement of other claims (Compl. ¶2, ¶70).
U.S. Patent No. 11,690,854 - Methods of Treating Heavy Menstrual Bleeding
Issued July 4, 2023
The Invention Explained
- Problem Addressed: The patent addresses the treatment of heavy menstrual bleeding (HMB), a symptom associated with conditions like uterine fibroids, which can cause inconvenience and lead to iron-deficiency anemia (’854 Patent, col. 1:35-43).
- The Patented Solution: The patent claims methods of treating HMB or endometriosis-associated pain by administering elagolix concomitantly with omeprazole, a common proton pump inhibitor (’854 Patent, Abstract; col. 27:40-50). The claims define a specific dosing regimen where the omeprazole dose is not adjusted from a standard 40 mg once-per-day schedule (’854 Patent, col. 27:46-50).
- Technical Importance: The invention provides a specific method for co-administering elagolix and omeprazole, clarifying for prescribers that no dose adjustment for omeprazole is needed, which simplifies treatment for patients with co-morbid conditions.
Key Claims at a Glance
- The complaint asserts at least one claim of the '854 Patent (Compl. ¶91). Independent claim 1 is representative:
- A method for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) or management of moderate to severe pain associated with endometriosis,
- the method comprising: orally administering to a patient in need thereof elagolix sodium,
- wherein the patient concomitantly receives omeprazole,
- wherein the omeprazole is administered without an adjustment to a recommended omeprazole dosing schedule, and
- the recommended omeprazole dosing schedule comprises a 40 mg dose administered once per day.
- The complaint reserves the right to assert infringement of other claims (Compl. ¶2, ¶94).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendants' proposed generic elagolix sodium oral tablets, for which approval is sought from the FDA via ANDA No. 217296 (Compl. ¶1, ¶61).
Functionality and Market Context
- The complaint alleges that the Defendants' generic product is a copy of AbbVie's ORILISSA® tablets, containing the same active ingredient (elagolix sodium) in equivalent 150 mg and 200 mg base dosage forms (Compl. ¶1, ¶61).
- The infringement is based on the filing of the ANDA. The complaint alleges that in the ANDA, Defendants have represented to the FDA that their generic product is "pharmaceutically and therapeutically equivalent" to ORILISSA® (Compl. ¶68, ¶92). The intended use is for the management of moderate to severe pain associated with endometriosis, the same indication as ORILISSA® (Compl. ¶7, ¶61).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint. The complaint does not provide a claim chart exhibit or detailed infringement contentions mapping specific elements of the proposed generic product or its label to the patent claims. The infringement theory is based on inducement, alleging that the proposed product label will instruct healthcare providers and patients to use the generic drug in a manner that directly infringes the asserted method claims (Compl. ¶72-74, ¶96-98).
'845 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating a gynecological disorder... comprising orally administering to the patient... elagolix sodium... | On information and belief, Defendants' proposed package insert will instruct healthcare professionals and patients to use the generic product to treat a gynecological disorder (endometriosis). | ¶72; ¶74 | col. 2:50-56 |
| wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily; wherein the patient receives a once daily dose of 150 mg of bupropion... | The complaint does not provide sufficient detail for analysis of how the proposed label instructs this specific co-administration, but alleges that use according to the label will directly infringe. | ¶70; ¶74 | col. 2:50-58 |
| wherein... [a specific set of four pharmacokinetic parameter ratios are achieved] | The complaint does not provide specific facts on how the accused use will result in these PK ratios, but alleges that the product described in the ANDA would infringe. | ¶67 | col. 2:59-65; col. 3:1-4 |
'854 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for management of heavy menstrual bleeding... or management of moderate to severe pain associated with endometriosis... comprising: orally administering to a patient in need thereof elagolix sodium... | On information and belief, Defendants' proposed package insert will instruct healthcare professionals and patients to use the generic product for the management of pain associated with endometriosis. | ¶96; ¶98 | col. 27:40-45 |
| wherein the patient concomitantly receives omeprazole... | The complaint does not provide specific facts on how the proposed label instructs this concomitant use, but alleges that patients will take the generic product in a way that infringes. | ¶96 | col. 27:45-46 |
| wherein the omeprazole is administered without an adjustment to a recommended omeprazole dosing schedule and the recommended omeprazole dosing schedule comprises a 40 mg dose administered once per day. | The complaint does not provide sufficient detail for analysis of how the proposed label instructs this specific dosing regimen, but alleges infringement will occur. | ¶94; ¶98 | col. 27:46-50 |
Identified Points of Contention
- Evidentiary Questions: A primary question will be what evidence AbbVie can present from the Defendants' ANDA submission, particularly the proposed product label, to demonstrate that the label's instructions will induce infringement. For the ’845 Patent, this raises the question of whether the label must specifically mention co-administration with bupropion and the resulting PK effects, or if more general language would suffice.
- Scope Questions: For the ’854 Patent, a key issue may be the construction and application of the negative limitation "without an adjustment." The dispute may center on whether the absence of a dose-adjustment warning on the generic label is sufficient to meet this limitation, or if an affirmative statement of "no adjustment needed" is required.
V. Key Claim Terms for Construction
For the ’845 Patent
- The Term: "a ratio of Cmax for bupropion following co-administration... to Cmax for bupropion... alone is between about 1.104 and about 1.407" (and the other three PK ratio limitations).
- Context and Importance: This term is a pharmacokinetic result, not an action taken by a user. Infringement of such a claim element often turns on whether the administration of the drug according to the label necessarily results in the claimed outcome. Practitioners may focus on the word "about," which provides some range, and the evidentiary challenge of proving this PK result occurs in patients following the proposed label.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of "about" throughout the specification and claims suggests the inventors did not intend the numerical ranges to be exact and absolute, allowing for some experimental variability (’845 Patent, col. 2:59-62).
- Evidence for a Narrower Interpretation: The patent provides highly specific data from a clinical study, including precise calculated ratios and confidence intervals (e.g., a Cmax ratio of 1.246 with a 90% CI of 1.104-1.407) (’845 Patent, Table 2; FIG. 3). A party could argue the term "about" should be construed narrowly in light of these specific examples.
For the ’854 Patent
- The Term: "administered without an adjustment to a recommended omeprazole dosing schedule"
- Context and Importance: This negative limitation is central to Claim 1. Its construction will determine what the proposed generic label must (or must not) say regarding co-administration with omeprazole. Practitioners may focus on whether silence on the label regarding dose adjustment satisfies this limitation, or if an affirmative instruction is needed.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discusses that in some cases, "no dose adjustment is needed for omeprazole at total daily doses of 40 mg or less when co-administered with elagolix sodium" (’854 Patent, col. 12:24-28). A party could argue this supports a view that the lack of a need for adjustment is the core of the invention, and a label that is silent on the matter correctly reflects this.
- Evidence for a Narrower Interpretation: The patent also provides for situations where a "dose adjustment is needed," particularly for higher doses of omeprazole (’854 Patent, col. 12:40-44). A party could argue that to distinguish from these situations, the "without an adjustment" limitation requires an explicit instruction to maintain the standard dose, rather than mere silence.
VI. Other Allegations
Indirect Infringement
- The complaint alleges induced infringement for both patents. The basis is the allegation that Defendants know, or should know, that the instructions in their proposed package insert will cause healthcare professionals and patients to use the generic product in a way that directly infringes the claimed methods (Compl. ¶72-74, ¶96-98).
Willful Infringement
- The complaint does not use the term "willful infringement." However, it alleges that Defendants have knowledge of the patents through their listing in the FDA's Orange Book (Compl. ¶64, ¶97) and requests a finding that this is an "exceptional case" warranting an award of attorney fees (Compl. ¶117(G)), which is often associated with findings of willful or egregious conduct.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of induced infringement and evidence: Given the general nature of the complaint, the case will depend on the specific language of the Defendants' proposed generic drug label. A key question for the court will be whether the label's instructions are specific enough to encourage, recommend, or promote the exact methods of use recited in the patent claims, particularly the complex pharmacokinetic outcomes required by the '845 Patent and the specific non-adjustment for omeprazole dosing in the '854 Patent.
- A central claim construction question will be the scope of negative limitations: The infringement analysis for the '854 Patent will turn on the meaning of "without an adjustment." The court will need to determine whether infringement of this negative limitation can be established by a label's silence on dose adjustment, or if it requires an affirmative instruction to maintain the standard dose, thereby setting the evidentiary bar for what AbbVie must prove from the contents of the ANDA.