DCT
1:17-cv-01347
Shionogi Inc v. Qingdao Baheal Pharmaceutical Co Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Shionogi Inc. (Delaware) and Andrx Labs, L.L.C. (Delaware)
- Defendant: Qingdao Baheal Pharmaceutical Co. Ltd. (China)
- Plaintiff’s Counsel: Bayard, P.A.; Wilmer Cutler Pickering Hale & Dorr LLP
- Case Identification: 1:17-cv-01347, D. Del., 09/22/2017
- Venue Allegations: Plaintiffs allege venue is proper for a foreign corporation in any judicial district and that personal jurisdiction exists due to Defendant’s filing of an Abbreviated New Drug Application (ANDA) with the FDA, which purposefully directs future commercial activity toward the United States, including Delaware.
- Core Dispute: Plaintiffs allege that Defendant’s filing of an ANDA to market a generic version of Plaintiffs' FORTAMET® tablets constitutes an act of infringement of two patents covering controlled-release metformin formulations and methods of use.
- Technical Context: The technology relates to oral pharmaceutical compositions for metformin, a primary treatment for Type 2 diabetes, specifically formulations designed to release the drug over an extended period to allow for once-daily dosing.
- Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Defendant's ANDA submission (No. 20-9993) and a Paragraph IV certification asserting the patents-in-suit are invalid, unenforceable, or will not be infringed. The patents are listed in the FDA's "Orange Book" for FORTAMET®. U.S. Patent No. 6,866,866 was the subject of a subsequent Inter Partes Review (IPR2017-01648), which concluded with a certificate confirming all challenged claims (1-25) as patentable.
Case Timeline
| Date | Event |
|---|---|
| 2000-11-03 | Priority Date for ’459 and ’866 Patents |
| 2004-09-14 | U.S. Patent No. 6,790,459 Issued |
| 2005-03-15 | U.S. Patent No. 6,866,866 Issued |
| 2017-08-09 | Plaintiffs Receive Defendant's Notice Letter |
| 2017-09-22 | Complaint Filing Date |
| 2019-08-02 | IPR Certificate Issued Confirming '866 Patent Claims |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,790,459 - "Methods for Treating Diabetes Via Administration of Controlled Release Metformin," Issued September 14, 2004
The Invention Explained
- Problem Addressed: The patent's background section notes that immediate-release metformin, a widely prescribed drug for non-insulin-dependent diabetes mellitus (NIDDM), is short-acting and requires frequent (twice or thrice daily) dosing, which can cause gastrointestinal side effects and reduce patient compliance ('459 Patent, col. 2:5-12).
- The Patented Solution: The invention is a method of treating NIDDM by administering a controlled-release metformin dosage form once per day. The formulation is designed to achieve a specific pharmacokinetic profile, including a mean time to maximum plasma concentration (Tmax) of 5.5 to 7.5 hours after being taken with dinner ('459 Patent, col. 3:20-32). This timing is intended to deliver the highest drug concentration when the body’s natural glucose production (gluconeogenesis) is at its peak overnight ('459 Patent, col. 9:6-10).
- Technical Importance: By enabling a once-daily dosing regimen with a targeted release profile, the invention aimed to improve therapy for NIDDM patients by enhancing convenience and potentially reducing side effects associated with conventional metformin products ('459 Patent, col. 2:10-17).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 ('459 Patent, Compl. ¶33).
- Essential Elements of Independent Claim 1:
- A method of lowering blood glucose in NIDDM patients by orally administering, on a once-a-day basis, at least one oral controlled-release dosage form of metformin.
- Following a single dose administration with dinner, the dosage form provides a mean Tmax of metformin from 5.5 to 7.5 hours.
- The administration provides specific mean AUC (area under the curve) and Cmax (maximum concentration) values on day 1 and day 14 of treatment for a 2000 mg dose.
U.S. Patent No. 6,866,866 - "Controlled Release Metformin Compositions," Issued March 15, 2005
The Invention Explained
- Problem Addressed: The '866 Patent addresses the same technical problem as its parent '459 Patent: the need for a more convenient, once-daily metformin formulation to improve on the twice- or thrice-daily immediate-release versions ('866 Patent, col. 2:4-17).
- The Patented Solution: Rather than claiming a method of use, this patent claims the pharmaceutical composition itself. The invention is an oral controlled-release dosage form of metformin suitable for once-daily administration which, when administered after dinner, provides a mean Tmax between 5.5 and 7.5 hours ('866 Patent, Abstract). The specification describes a preferred embodiment as an osmotic tablet comprising a core with the drug and a surrounding membrane with at least one passageway to control the drug's release ('866 Patent, col. 6:11-20).
- Technical Importance: The patent provided protection for a tangible product that embodied the pharmacokinetic solution for once-daily metformin therapy, moving beyond the method of treatment to the specific drug delivery system ('866 Patent, col. 2:10-17).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 ('866 Patent, Compl. ¶38).
- Essential Elements of Independent Claim 1:
- A controlled release oral dosage form for reducing serum glucose levels in NIDDM patients, comprising an effective dose of metformin and a controlled-release carrier.
- The dosage form is suitable for once-a-day oral administration.
- Following a single dose administration with dinner, the dosage form provides a mean Tmax of metformin from 5.5 to 7.5 hours.
III. The Accused Instrumentality
Product Identification
- Defendant’s proposed generic Metformin Extended Release 500 mg and 1000 mg Tablets, identified in the complaint as the "Baheal ANDA Products" and the subject of ANDA No. 20-9993 (Compl. ¶¶ 1, 23).
Functionality and Market Context
- The complaint alleges the Baheal ANDA Products are a generic version of Plaintiffs' branded FORTAMET® tablets (Compl. ¶1).
- Based on the ANDA filing, Defendant represents that its product has the same active ingredient, dosage form, strength, and administration method as FORTAMET®, and that it is bioequivalent to FORTAMET® (Compl. ¶¶ 25, 33, 38).
- The product is intended for the U.S. market to treat adults with Type 2 diabetes mellitus, an indication that mirrors that of FORTAMET® (Compl. ¶¶ 20, 25). The complaint notes that Defendant’s website promotes its specialization in extended-release pharmaceuticals for the U.S. market (Compl. ¶11). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’459 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for lowering blood glucose levels...comprising orally administering to human patients on a once-a-day basis at least one oral controlled release dosage form comprising an effective dose of metformin... | Defendant's ANDA seeks approval to market controlled-release metformin tablets for lowering blood glucose. The proposed product label will allegedly instruct for once-a-day administration by patients and medical practitioners. | ¶¶ 31, 33 | col. 21:13-21 |
| wherein following oral administration of a single dose, the dosage form provides a mean time to maximum plasma concentration (Tmax) of metformin at from 5.5 to 7.5 hours after administration following dinner; | The complaint alleges that by filing an ANDA asserting bioequivalence to FORTAMET®, Defendant has represented to the FDA that its product will exhibit the same pharmacokinetic profile, including the claimed Tmax range when administered as directed. | ¶¶ 25, 33 | col. 21:22-26 |
| and the administration...provides a mean AUC... and a mean Cmax... on the first day... and... on the 14th day of administration, for administration of a 2000 mg once-a-day dose of metformin. | The complaint alleges that the required representation of bioequivalence in the ANDA filing necessarily means that Defendant's product will meet the specific AUC and Cmax pharmacokinetic parameters recited in the claim. | ¶¶ 25, 33 | col. 21:26-31 |
’866 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A controlled release oral dosage form for the reduction of serum glucose levels in human patients with NIDDM, comprising an effective dose of metformin or a pharmaceutically acceptable salt thereof and a controlled-release carrier... | Defendant’s Baheal ANDA Products are described as "controlled release dosage form[s]" comprising "an effective dose of metformin" for use in treating NIDDM. | ¶¶ 33, 38 | col. 21:48-55 |
| ...said dosage form being suitable for providing once-a-day oral administration... | Defendant seeks approval for a generic version of FORTAMET®, which is a once-a-day product, and its proposed product will allegedly be administered accordingly. | ¶¶ 25, 38 | col. 21:56-57 |
| ...wherein following oral administration of a single dose, the dosage form provides a mean time to maximum plasma concentration (Tmax) of the metformin from 5.5 to 7.5 hours after administration following dinner. | The allegation of infringement is based on the legal representation of bioequivalence to FORTAMET® made in the ANDA filing. The complaint asserts this representation means the accused product must exhibit the claimed pharmacokinetic Tmax profile. | ¶¶ 25, 38 | col. 21:58-61 |
Identified Points of Contention
- Evidentiary Question: The complaint notes that the parties have not reached an agreement for Plaintiffs to access the confidential ANDA submission (Compl. ¶26). Therefore, the central dispute will be evidentiary. A key question for the court will be whether the product as described in Defendant's confidential ANDA, including its bioequivalence studies, demonstrates pharmacokinetic parameters (Tmax, AUC, Cmax) that literally meet the ranges recited in the asserted claims.
- Scope Question: The claims are defined by specific numerical pharmacokinetic ranges. The infringement analysis may raise questions about the precise boundaries of these ranges. For instance, if Defendant's product exhibits a Tmax just outside the "5.5 to 7.5 hours" window, a dispute over literal infringement versus the doctrine of equivalents could arise.
V. Key Claim Terms for Construction
The Term: "mean time to maximum plasma concentration (Tmax) ... from 5.5 to 7.5 hours" ('459, cl. 1; '866, cl. 1)
- Context and Importance: This pharmacokinetic range is a central limitation in the independent claims of both patents. The infringement determination will likely depend on whether the accused product's performance falls within this precise window.
- Intrinsic Evidence for a Broader Interpretation: The specification mentions related but different time ranges, such as "from 6.0 to 7.0" hours, which a party might argue suggests the claimed range is exemplary rather than a strict limit ('459 Patent, col. 3:19-20).
- Intrinsic Evidence for a Narrower Interpretation: The claims explicitly recite the "5.5 to 7.5 hours" range. The patent's abstract, summary, and the data from clinical studies all emphasize this specific window, which a party could use to argue that the patentee intentionally selected and is bound by these precise numerical endpoints ('459 Patent, Abstract; col. 18, Table 1).
The Term: "following dinner" ('459, cl. 1; '866, cl. 1)
- Context and Importance: This term ties the claimed pharmacokinetic performance to a specific "fed state" condition. The interpretation of this term is critical because it defines the conditions under which infringement must be assessed. Practitioners may focus on this term because bioequivalence studies are conducted under highly controlled conditions that may or may not align with the patent's definition.
- Intrinsic Evidence for a Broader Interpretation: The specification defines "dinnertime" as a general time of day ("generally between about 4 p.m. and 8 p.m.") "regardless of whether a meal is actually eaten" unless specified ('459 Patent, col. 7:14-19). This could support an interpretation that is not strictly tied to the act of eating.
- Intrinsic Evidence for a Narrower Interpretation: The claim language is "following dinner," not "at dinnertime." The specification's clinical studies describe administration "immediately following dinner," and the patent repeatedly emphasizes the advantages of administration with food ('459 Patent, col. 16:50-54). A party could argue this requires administration in close temporal proximity to an actual evening meal.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendant will induce infringement by patients and doctors by providing a product with a label that instructs users to take it in a manner that directly infringes the method claims of the '459 Patent (Compl. ¶31). It also alleges contributory infringement, stating the Baheal ANDA Products are especially made for this infringing use and have no substantial non-infringing use (Compl. ¶32).
- Willful Infringement: The complaint does not explicitly allege "willful infringement." However, it alleges that Defendant's inducement would be "actively, intentionally, and knowingly" done and that its actions will occur with "knowledge and specific intent" (Compl. ¶¶ 30, 31). This is predicated on the knowledge provided by the Notice Letter sent prior to the lawsuit (Compl. ¶23).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be evidentiary and factual: Does the product described in Defendant's confidential ANDA filing, particularly its bioequivalence data, demonstrate a pharmacokinetic profile (Tmax, AUC, Cmax) that falls literally within the numerical ranges recited in the asserted claims?
- The case will also turn on a question of claim construction: Can the claimed pharmacokinetic range of a Tmax "from 5.5 to 7.5 hours" be interpreted with any flexibility, or is it a strict boundary that defines the scope of the invention? The court's interpretation of this and other terms like "following dinner" will be dispositive for the infringement analysis.
- A third key question relates to patent validity: Given that the '866 patent has already survived an Inter Partes Review, can Defendant present clear and convincing evidence of invalidity based on prior art or legal arguments that were not already considered and rejected by the Patent Trial and Appeal Board?