DCT
1:16-cv-00026
Purdue Pharma LP v. Alvogen Pine Brook LLC
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Purdue Pharma L.P. (Delaware)
- Defendant: Alvogen Pine Brook, LLC (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Fried Frank Harris Shriver & Jacobson LLP
- Case Identification: 1:16-cv-00026, D. Del., 01/20/2016
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is a Delaware corporation and has previously submitted to the jurisdiction of the court.
- Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's Hysingla® ER opioid analgesic constitutes an act of infringement of two patents covering controlled-release hydrocodone formulations.
- Technical Context: The lawsuit concerns extended-release oral opioid formulations, a technology designed to provide around-the-clock pain relief with once-daily dosing, which is a significant segment of the pharmaceutical market for pain management.
- Key Procedural History: This action follows three prior lawsuits filed by Purdue against Alvogen in 2015 concerning other patents related to Hysingla® ER. Those actions were consolidated. The current lawsuit arises under the Hatch-Waxman Act, triggered by Defendant’s Paragraph IV certification asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by its proposed generic products.
Case Timeline
| Date | Event |
|---|---|
| 2000-10-30 | Earliest Priority Date for ’863 and ’056 Patents |
| 2015-06-19 | Defendant Files ANDA No. 208269 (on or before this date) |
| 2015-08-05 | Plaintiff Files Related Complaint (C.A. No. 15-687) |
| 2015-09-04 | Plaintiff Files Related Complaint (C.A. No. 15-784) |
| 2015-10-16 | Plaintiff Files Related Complaint (C.A. No. 15-940) |
| 2015-11-17 | Prior Civil Actions are Consolidated |
| 2015-12-01 | U.S. Patent No. 9,198,863 Issues |
| 2015-12-08 | U.S. Patent No. 9,205,056 Issues |
| 2016-01-11 | Plaintiff Receives Paragraph IV Notice Letter (on or about this date) |
| 2016-01-20 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,198,863 - "CONTROLLED RELEASE HYDROCODONE FORMULATIONS," issued December 1, 2015
The Invention Explained
- Problem Addressed: The patent seeks to address the need for improved efficiency and quality in managing moderate to severe pain, which often requires long-term, around-the-clock treatment (Compl. ¶7; ’863 Patent, col. 1:40-45).
- The Patented Solution: The invention is a solid, oral, once-a-day controlled-release hydrocodone tablet. Its key innovation is achieving a specific pharmacokinetic profile where, after an initial rise, the drug’s plasma concentration remains relatively stable over a 24-hour period. This is defined by a C24/Cmax ratio (the drug concentration at 24 hours divided by the peak concentration) of about 0.55 to 1.0, which provides sustained pain relief without the sharp peaks and troughs of immediate-release formulations (’863 Patent, Abstract; col. 2:60-66).
- Technical Importance: A once-daily formulation with a flattened plasma profile can enhance patient compliance and provide more consistent analgesia, potentially reducing breakthrough pain and the side effects associated with high peak drug concentrations (’863 Patent, col. 1:46-54).
Key Claims at a Glance
- The complaint asserts independent claims 1, 12, 21, and 28 (Compl. ¶23).
- Independent Claim 1 recites:
- A solid oral controlled-release dosage form of hydrocodone, which is a tablet;
- Comprising a bitartrate salt of hydrocodone and a poly(alkylene oxide);
- Which, after administration to a human subject, provides a C24/Cmax hydrocodone ratio of from about 0.55 to about 1.0;
- Wherein the amount of hydrocodone is from about 0.5 mg to about 1250 mg; and
- Wherein the bitartrate salt of hydrocodone is the only active agent in the dosage form.
- The complaint reserves the right to assert additional claims, including dependent claims (Compl. ¶23).
U.S. Patent No. 9,205,056 - "CONTROLLED RELEASE HYDROCODONE FORMULATIONS," issued December 8, 2015
The Invention Explained
- Problem Addressed: Similar to the ’863 patent, this patent addresses the objective of improving the management of moderate pain through a more efficient once-a-day formulation (’056 Patent, col. 1:45-48).
- The Patented Solution: This patent, part of the same family as the ’863 patent, also describes a once-daily, controlled-release hydrocodone tablet designed to achieve a relatively flat plasma concentration profile. The key inventive concept is again the specific C24/Cmax ratio of about 0.55 to 1.0. However, the claims of this patent specify a different formulation structure, namely a "matrix" that includes microcrystalline cellulose as a key component (’056 Patent, Abstract; col. 25:1-10).
- Technical Importance: This patent provides an alternative formulation pathway (a microcrystalline cellulose matrix) to achieve the same clinically significant goal of stable, 24-hour analgesic plasma levels described in the ’863 patent (’056 Patent, col. 1:51-58).
Key Claims at a Glance
- The complaint asserts independent claims 1, 12, 21, and 28 (Compl. ¶33).
- Independent Claim 1 recites:
- A solid oral controlled-release dosage form of hydrocodone, which is a tablet;
- Comprising a "matrix" comprising a bitartrate salt of hydrocodone and microcrystalline cellulose;
- Which, after administration to a human subject, provides a C24/Cmax hydrocodone ratio of from about 0.55 to about 1.0;
- Wherein the amount of hydrocodone is from about 0.5 mg to about 1250 mg; and
- Wherein the bitartrate salt of hydrocodone is the only active agent in the dosage form.
- The complaint reserves the right to assert additional claims, including dependent claims (Compl. ¶33).
III. The Accused Instrumentality
Product Identification
- Defendant’s proposed generic versions of Purdue’s Hysingla® ER (hydrocodone bitartrate) in 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg, and 120 mg dosage strengths, as described in ANDA No. 208269 ("Defendant's ANDA Products") (Compl. ¶1).
Functionality and Market Context
- The accused instrumentalities are extended-release oral tablets intended for daily, around-the-clock, long-term opioid treatment (Compl. ¶1, ¶7). As generic products, they are intended to be bioequivalent to the reference listed drug, Hysingla® ER (Compl. ¶16). The act of infringement alleged is the submission of the ANDA to the FDA seeking approval to market these products in the United States, which represents a direct commercial challenge to Purdue's branded drug (Compl. ¶1, ¶19).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
The complaint alleges infringement under 35 U.S.C. § 271(e)(2), which makes the submission of an ANDA for a drug claimed in a patent an act of infringement. The core allegation is that the product described in the ANDA, if approved and marketed, would infringe the patents-in-suit (Compl. ¶22, ¶32). The complaint does not contain a detailed claim chart, but the infringement theory can be summarized.
'863 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A solid oral controlled-release dosage form of hydrocodone ... wherein the dosage form is a tablet | Defendant's ANDA Products are alleged to be solid oral controlled-release hydrocodone tablets. | ¶1, ¶23 | col. 2:3-4 |
| comprising a bitartrate salt of hydrocodone and a poly(alkylene oxide) | The complaint alleges that the ANDA Products are covered by the claims of the '863 patent, which is listed in the FDA's Orange Book for Hysingla® ER. By seeking to market a generic version, Defendant's product is alleged to contain the claimed formulation. | ¶14, ¶16, ¶23 | col. 25:9-10 |
| which, after administration to a human subject, provides a C24/Cmax hydrocodone ratio of from about 0.55 to about 1.0 | As a proposed generic of Hysingla® ER, the ANDA Products must be bioequivalent to the reference drug, which Plaintiff alleges exhibits the claimed pharmacokinetic profile. | ¶16, ¶17, ¶23 | col. 2:11-12 |
| wherein the bitartrate salt of hydrocodone is the only active agent in the dosage form | The ANDA Products are generic versions of Hysingla® ER, which is a single-entity hydrocodone product. | ¶1, ¶7 | col. 25:17-18 |
'056 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A solid oral controlled-release dosage form of hydrocodone ... wherein the dosage form is a tablet | Defendant's ANDA Products are alleged to be solid oral controlled-release hydrocodone tablets. | ¶1, ¶33 | col. 25:1-3 |
| comprising a matrix comprising a bitartrate salt of hydrocodone and microcrystalline cellulose | The complaint alleges that the ANDA Products are covered by the claims of the '056 patent, which is listed in the FDA's Orange Book for Hysingla® ER. By seeking to market a generic version, Defendant's product is alleged to contain the claimed formulation. | ¶15, ¶16, ¶33 | col. 13:3-10 |
| which, after administration to a human subject, provides a C24/Cmax hydrocodone ratio of from about 0.55 to about 1.0 | As a proposed generic of Hysingla® ER, the ANDA Products must be bioequivalent to the reference drug, which Plaintiff alleges exhibits the claimed pharmacokinetic profile. | ¶16, ¶17, ¶33 | col. 25:6-8 |
| wherein the bitartrate salt of hydrocodone is the only active agent in the dosage form | The ANDA Products are generic versions of Hysingla® ER, which is a single-entity hydrocodone product. | ¶1, ¶7 | col. 25:15-16 |
- Identified Points of Contention:
- Technical Questions: The central technical dispute will be one of non-infringement, as asserted in Defendant's Paragraph IV certification (Compl. ¶17). The key question is whether Defendant has successfully "designed around" the patent claims. Does the formulation in the ANDA use different excipients (e.g., something other than poly(alkylene oxide) for the ’863 Patent, or a structure other than a "matrix" with microcrystalline cellulose for the ’056 Patent) to achieve controlled release? The complaint does not provide these details.
- Scope Questions: The case will likely involve a significant dispute over the scope of the pharmacokinetic limitations. Does the bioequivalence data submitted in Defendant’s ANDA demonstrate a C24/Cmax ratio that is definitively outside the claimed range of "from about 0.55 to about 1.0"? The interpretation of the word "about" could be determinative.
V. Key Claim Terms for Construction
The Term: "C24/Cmax hydrocodone ratio of from about 0.55 to about 1.0" (’863 Patent, Claim 1; ’056 Patent, Claim 1)
- Context and Importance: This pharmacokinetic parameter is the quantitative heart of the invention, defining the "flat" plasma profile that enables once-daily dosing. Infringement will be determined by comparing the accused product’s performance to this range. Practitioners may focus on this term because the scope of "about" will dictate whether a product with a ratio close to, but not exactly within, 0.55-1.0 infringes.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification repeatedly uses the word "about" when discussing the claimed ratio and other numerical parameters, which may suggest the patentee did not intend to be held to the precise numerical endpoints (’863 Patent, col. 2:11, col. 2:18, col. 2:65).
- Evidence for a Narrower Interpretation: The patent discloses specific formulation examples with measured dissolution data (e.g., ’863 Patent, Table 1B, col. 22:49-65). A party could argue that the scope of "about" should be informed by the precision and range of these examples.
The Term: "matrix" (’056 Patent, Claim 1)
- Context and Importance: Claim 1 of the ’056 patent requires the hydrocodone and microcrystalline cellulose to be in a "matrix." Defendant’s non-infringement defense could depend on arguing that its formulation does not constitute a "matrix" as that term is used in the patent. Practitioners may focus on this term because it defines the physical structure of the claimed dosage form.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The detailed description discusses multiple types of controlled-release formulations, including melt-extruded multiparticulates and coated beads, not just simple compressed tablets, which could support a non-limiting definition of the term (’056 Patent, col. 9:28-33; col. 14:36-42).
- Evidence for a Narrower Interpretation: The section titled "Controlled Release Matrix Formulations" describes a specific structure where a controlled-release material is incorporated "into a matrix along with the hydrocodone" (’056 Patent, col. 7:10-14). This could be used to argue for a narrower definition limited to a monolithic system where drug and excipients are intimately mixed.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that if the ANDA is approved, Defendant’s commercial activities will contribute to and induce infringement by others (e.g., physicians and patients) who would use the product as directed (Compl. ¶24, ¶28, ¶34, ¶38).
- Willful Infringement: Plaintiff alleges that the case is "exceptional" under 35 U.S.C. § 285. This is based on the allegation that Defendant was aware of the patents-in-suit and proceeded with its ANDA filing without a reasonable basis to believe its products would not infringe (Compl. ¶29, ¶39).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of technical non-infringement: Will discovery reveal that Defendant’s ANDA product employs a formulation that successfully designs around the specific excipients and structures claimed in the patents—namely, the "poly(alkylene oxide)" of the ’863 patent and the "microcrystalline cellulose matrix" of the ’056 patent?
- A key question of claim construction will determine the outcome: How broadly will the court interpret the term "about" in the context of the claimed "C24/Cmax" ratio? The resolution of this issue will define the boundary of infringement and whether the bioequivalence data for Defendant's product falls within the patents' scope.
- A third critical question, flowing from Defendant's Paragraph IV certification, will be one of validity: Although not detailed in the complaint, Defendant will be required to prove by clear and convincing evidence its assertion that the patents are invalid, likely focusing on whether achieving the claimed pharmacokinetic profile with hydrocodone was obvious in light of prior art controlled-release technologies.