DCT
1:19-cv-01727
Allergan USA Inc v. MSN Laboratories Pvt Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Allergan USA, Inc. (Delaware), Allergan Holdings Unlimited Company (Ireland), and Eden Biodesign, LLC (Delaware)
- Defendant: Sun Pharmaceutical Industries Limited (India)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; O’Melveny & Myers LLP
- Case Identification: 1:19-cv-01727, D. Del., 04/28/2022
- Venue Allegations: Venue is alleged to be proper because Defendant is a corporation organized under the laws of India and is subject to personal jurisdiction in the District of Delaware.
- Core Dispute: Plaintiffs allege that Defendant’s Abbreviated New Drug Application (ANDA) seeking approval to market a generic version of the drug Viberzi® (eluxadoline) constitutes an act of infringement of two recently issued U.S. patents covering specific drug formulations.
- Technical Context: The technology concerns solid oral dosage formulations for opioid receptor modulators used to treat gastrointestinal disorders, specifically irritable bowel syndrome with diarrhea (IBS-D).
- Key Procedural History: This First Amended Complaint adds two newly issued patents to a consolidated, ongoing litigation between the parties. The litigation began after Defendant filed ANDA No. 213447, challenging several other patents in the same family listed in the FDA's Orange Book for Viberzi®. The two patents-in-suit issued after the initial ANDA was filed and were subsequently added to the existing dispute.
Case Timeline
| Date | Event |
|---|---|
| 2013-03-14 | Earliest Priority Date for ’627 and ’516 Patents |
| 2019-07-31 | Defendant Sun submitted ANDA No. 213447 (on or before this date) |
| 2022-01-25 | U.S. Patent No. 11,229,627 Issued |
| 2022-04-26 | U.S. Patent No. 11,311,516 Issued |
| 2022-04-28 | First Amended Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,229,627 - “Opioid Receptor Modulator Dosage Formulations”
- Patent Identification: U.S. Patent No. 11,229,627, titled “Opioid Receptor Modulator Dosage Formulations,” issued January 25, 2022 (the “’627 Patent”).
The Invention Explained
- Problem Addressed: The patent background describes the need for effective pharmacologic treatments for irritable bowel syndrome with diarrhea (IBS-D), a common gastrointestinal disorder (’627 Patent, col. 2:1-13). It also notes that the active pharmaceutical ingredient, an opioid receptor modulator, can produce CNS-related effects when administered parenterally, which creates a potential for abuse (’627 Patent, col. 3:1-8).
- The Patented Solution: The invention is a specific solid oral dosage formulation of the active ingredient (eluxadoline) that uses a particular combination of excipients, including silicified microcrystalline cellulose and crospovidone, to create a stable and effective tablet (’627 Patent, col. 4:6-16; Tbl. 1). The formulation is also described as possessing "abuse deterrent" characteristics, which may limit the ease of extracting the active ingredient for misuse, such as by injection (’627 Patent, col. 3:36-44).
- Technical Importance: The claimed formulation provides a specific composition for an approved IBS-D treatment that is designed to be stable for oral delivery while also possessing characteristics intended to deter misuse and abuse of the opioid-based active ingredient (’627 Patent, col. 3:9-24).
Key Claims at a Glance
The complaint alleges infringement of "one or more claims" but does not identify specific claims (Compl. ¶21). Independent claim 1 is presented here for representative analysis.
- Independent Claim 1:
- A pharmaceutical tablet comprising about 75 mg or 100 mg of a specific opioid receptor modulator active ingredient.
- The tablet includes about 70-90% by weight of a combination of a first filler (mannitol) and a second filler.
- It includes about 3-7% by weight of a disintegrant.
- It includes about 0.55-0.95% by weight of colloidal silicon dioxide.
- It includes about 0.45-1% by weight of a lubricant.
- The tablet comprises at least 10% by weight mannitol.
- The complaint does not explicitly reserve the right to assert dependent claims, but the broad allegation of infringing "one or more claims" may be interpreted to include them (Compl. ¶21).
U.S. Patent No. 11,311,516 - “Opioid Receptor Modulator Dosage Formulations”
- Patent Identification: U.S. Patent No. 11,311,516, titled “Opioid Receptor Modulator Dosage Formulations,” issued April 26, 2022 (the “’516 Patent”).
The Invention Explained
- Problem Addressed: The technical problem is identical to that described for the ’627 Patent: formulating an oral opioid receptor modulator for IBS-D that is effective and stable, while also addressing the potential for abuse associated with the active ingredient (’516 Patent, col. 2:1-13; col. 3:1-8).
- The Patented Solution: The ’516 Patent claims a solid dosage formulation with a specific set of components and weight percentages, similar to the ’627 Patent (’516 Patent, Abstract). A key feature of the claimed solution is a functional limitation: when the formulation is extracted with water or saline under specified conditions, it produces a concentration of the active ingredient that is "less than or approximately 4 mg/ml" (’516 Patent, Claim 1). This property is presented as a feature that deters abuse by making it difficult to create a concentrated solution for injection (’516 Patent, col. 33:35-44).
- Technical Importance: This patent claims a specific formulation for an IBS-D treatment that is defined not only by its chemical composition but also by a functional, abuse-deterrent property related to its limited extractability in common solvents (’516 Patent, col. 3:36-44).
Key Claims at a Glance
The complaint alleges infringement of "one or more claims" but does not identify specific claims (Compl. ¶21). Independent claim 1 is presented here for representative analysis.
- Independent Claim 1:
- A pharmaceutical tablet comprising about 75 mg of a specific opioid receptor modulator active ingredient.
- The tablet includes about 60-80% by weight filler.
- It includes about 2-8% by weight disintegrant.
- It includes about 10% by weight mannitol.
- A functional limitation: wherein extraction of the tablet with water or saline at 25° C. for 12 hours produces a concentration of the active ingredient of less than or approximately 4 mg/ml.
- The complaint’s allegation of infringing "one or more claims" may be interpreted to include dependent claims (Compl. ¶21).
III. The Accused Instrumentality
Product Identification
- Defendant Sun's proposed generic oral tablet products containing 75 mg and 100 mg of eluxadoline as the active ingredient, as described in ANDA No. 213447 ("the Sun Generic Products") (Compl. ¶15).
Functionality and Market Context
- The accused instrumentality is a generic drug for which Sun is seeking FDA approval (Compl. ¶5, ¶15). The action is based on the statutory act of infringement under 35 U.S.C. § 271(e)(2), which makes the submission of an ANDA an act of infringement if the proposed generic product would infringe a valid patent upon commercialization (Compl. ¶21). The Sun Generic Products are intended to be a generic version of Plaintiffs’ Viberzi® brand eluxadoline tablets, which are approved for the treatment of IBS-D in adults (Compl. ¶5, ¶12). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint provides a generalized allegation that the Sun Generic Products will meet each element of one or more claims of the patents-in-suit, either literally or under the doctrine of equivalents (Compl. ¶24). The following tables summarize the infringement theory for representative independent claim 1 of each patent based on these allegations.
’627 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical tablet comprising about 75 mg or about 100 mg of 5-({[(2S)-2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid... | The Sun Generic Products are oral tablets containing 75 mg and 100 mg of eluxadoline, the same active ingredient. | ¶15, ¶24 | col. 15:10-21 |
| about 70-90% by weight of a combination of a first filler and a second filler, wherein the first filler is mannitol... | The Sun Generic Products, as described in ANDA No. 213447, allegedly contain fillers including mannitol in the claimed weight percentage range. | ¶15, ¶24 | col. 15:22-24 |
| about 3-7% by weight of a disintegrant... | The Sun Generic Products, as described in ANDA No. 213447, allegedly contain a disintegrant in the claimed weight percentage range. | ¶15, ¶24 | col. 15:25-25 |
| about 0.55-0.95% by weight of colloidal silicon dioxide... | The Sun Generic Products, as described in ANDA No. 213447, allegedly contain colloidal silicon dioxide in the claimed weight percentage range. | ¶15, ¶24 | col. 15:26-27 |
| wherein the tablet comprises at least 10% by weight mannitol. | The Sun Generic Products, as described in ANDA No. 213447, allegedly contain at least 10% by weight mannitol. | ¶15, ¶24 | col. 15:29-30 |
’516 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical tablet comprising about 75 mg of 5-({[(2S)-2-Amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid... | The Sun Generic Products are oral tablets containing 75 mg of eluxadoline, the same active ingredient. | ¶15, ¶24 | col. 34:1-10 |
| about 60-80% by weight filler... | The Sun Generic Products, as described in ANDA No. 213447, allegedly contain a filler in the claimed weight percentage range. | ¶15, ¶24 | col. 34:11-11 |
| about 2-8% by weight disintegrant... | The Sun Generic Products, as described in ANDA No. 213447, allegedly contain a disintegrant in the claimed weight percentage range. | ¶15, ¶24 | col. 34:12-12 |
| wherein extraction of the tablet with water or saline at 25° C. for 12 hours produces a concentration of [the active ingredient] of less than or approximately 4 mg/ml. | The Sun Generic Products, as described in ANDA No. 213447, allegedly possess the claimed abuse-deterrent extraction profile. | ¶24 | col. 34:15-20 |
- Identified Points of Contention:
- Scope Questions: A central point of contention may be the construction of the term "about" as it applies to the weight percentages of the various excipients claimed in the ’627 Patent. Similarly, the scope of "less than or approximately 4 mg/ml" in the ’516 Patent will be a critical issue for determining infringement.
- Technical Questions: The complaint does not provide specific evidence that the Sun Generic Products meet the functional limitation of Claim 1 of the ’516 Patent related to extractability. A key technical question will be what evidence exists within Sun's ANDA, or can be generated through testing, to demonstrate that its proposed generic product produces a concentration of "less than or approximately 4 mg/ml" under the claimed test conditions.
V. Key Claim Terms for Construction
The Term: "about" (appearing in claims of both patents)
- Context and Importance: This term modifies all numerical ranges for the drug formulation's components. Its interpretation will directly determine the scope of the claims and whether Sun’s formulation, which is designed to be bioequivalent, literally infringes. Practitioners may focus on this term because even small deviations in formulation percentages could place an accused product inside or outside the literal scope of the claims.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification uses "about" consistently when referring to dosage amounts and component percentages, suggesting the patentee did not intend for the numerical values to be exact and precise endpoints (’627 Patent, col. 9:46-52).
- Evidence for a Narrower Interpretation: The patents provide specific formulation examples with precise weight percentages (e.g., 71.0% silicified microcrystalline cellulose, 5.0% crospovidone), which a defendant might argue should limit the scope of "about" to values very close to those exemplified (’627 Patent, Tbl. 1).
The Term: "wherein extraction of the tablet with water or saline at 25° C. for 12 hours produces a concentration of [the active ingredient] of less than or approximately 4 mg/ml" (’516 Patent, Claim 1)
- Context and Importance: This functional limitation is the core of the asserted abuse-deterrent property in the ’516 Patent. The infringement analysis for this patent will likely depend entirely on whether Sun's product meets this requirement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes a series of detailed "Abuse Liability Assessment" studies designed to test the formulation's resistance to extraction under various conditions, which may support an interpretation that any formulation exhibiting this functional property, regardless of minor compositional differences, falls within the claim (’516 Patent, col. 18-32).
- Evidence for a Narrower Interpretation: Table 12 in the specification presents specific concentration results from extraction experiments (’516 Patent, col. 33). A defendant may argue that the term should be construed in the specific context of the testing protocols and results disclosed in the specification, potentially limiting its scope to products that behave identically to the tested embodiments.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Sun will induce and contribute to infringement by doctors, pharmacists, and patients (Compl. ¶25, ¶26). This allegation is based on the prospective commercialization of the Sun Generic Products with a proposed package insert and prescribing information that will allegedly instruct users on an infringing use of the product (Compl. ¶24).
- Willful Infringement: The complaint does not contain an explicit count for willful infringement. However, it alleges that Sun's actions render this an "exceptional case" under 35 U.S.C. § 285 and requests attorneys' fees (Compl. ¶27, Prayer d). This allegation is predicated on Sun's continued pursuit of its ANDA after receiving notice of the patents-in-suit through this litigation. The complaint does not allege pre-suit knowledge, as the patents issued shortly before the filing of this amended complaint.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim scope: How broadly will the court construe the term "about" in relation to the claimed weight percentages in the ’627 Patent, and the phrase "less than or approximately 4 mg/ml" in the functional limitation of the ’516 Patent? The outcomes of these claim construction disputes may be dispositive of infringement.
- A key evidentiary question will be one of functional performance: As this is a Hatch-Waxman action based on an ANDA filing, a central dispute will be whether Plaintiffs can prove, by a preponderance of the evidence, that Sun's proposed generic product meets the specific abuse-deterrent extraction profile recited in the claims of the ’516 Patent.
- The case will also present a question of validity: Although not yet raised in a responsive pleading, Defendant will likely challenge the validity of these formulation patents as being obvious over the prior art, consistent with its certifications regarding other patents in the same family (Compl. ¶16). The ultimate question for the court will be whether the specific combination of excipients and the resulting functional properties were non-obvious at the time of the invention.