Genentech Inc v. Torrent Pharma Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Genentech, Inc. (Delaware) and InterMune, Inc. (Delaware)
  • Defendant: Torrent Pharmaceuticals Ltd. (India) and Torrent Pharma Inc. (Delaware)
  • Plaintiff’s Counsel: Morris Nichols Arsht & Tunnell LLP
• Case Identification: Genentech, Inc. v. Torrent Pharmaceuticals Ltd., 1:19-cv-00324, D. Del., 02/14/2019
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Torrent Pharma Inc. is a Delaware corporation and therefore resides in the district.
• Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) seeking FDA approval to market a generic version of the drug Esbriet® (pirfenidone) constitutes an act of infringement of two U.S. patents covering the drug's formulation and methods of use.
• Technical Context: The dispute centers on pharmaceutical treatments for Idiopathic Pulmonary Fibrosis (IPF), a rare, progressive, and fatal lung disease characterized by scarring of the lungs.
• Key Procedural History: The action was initiated under the Hatch-Waxman Act following a notice letter dated February 6, 2019, in which Torrent informed Plaintiffs of its ANDA filing and its Paragraph IV certification asserting that the patents-in-suit are invalid, unenforceable, and/or will not be infringed. The complaint notes that Plaintiffs' drug, Esbriet®, was granted Orphan Drug Exclusivity by the FDA, running until October 15, 2021.

Case Timeline

Date	Event
2005-09-22	U.S. Patent No. 8,383,150 Priority Date
2010-01-01	FDA initially denied approval for Esbriet® (approximate date)
2012-08-31	U.S. Patent No. 8,778,947 Priority Date
2013-02-26	U.S. Patent No. 8,383,150 Issued
2014-07-15	U.S. Patent No. 8,778,947 Issued
2014-10-15	FDA approved first New Drug Application (NDA) for Esbriet®
2019-02-06	Torrent sent notice letter to Plaintiffs regarding ANDA filing
2019-02-14	Complaint Filed
2021-10-15	Esbriet® Orphan Drug Exclusivity expiration date

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 8,383,150 - "Granulate Formulation of Pirfenidone and Pharmaceutically Acceptable Excipients"

• Patent Identification: U.S. Patent No. 8383150, "Granulate Formulation of Pirfenidone and Pharmaceutically Acceptable Excipients," issued February 26, 2013.

The Invention Explained

• Problem Addressed: The patent background describes a general need for effective pharmaceutical formulations of the anti-fibrotic drug pirfenidone that can produce desirable pharmacokinetic (PK) responses in patients, thereby optimizing the drug's therapeutic effects (ʼ150 Patent, col. 2:10-14).
• The Patented Solution: The invention is a capsule formulation containing pirfenidone and specific pharmaceutically acceptable excipients, including a binder. This formulation is designed to create a "prolonged absorption phase," which results in a significant increase in the drug's total exposure in the body (measured as Area Under the Curve, or AUC) compared to a formulation of pirfenidone without such excipients (ʼ150 Patent, Abstract; col. 8:49-65).
• Technical Importance: By controlling the drug's release and absorption profile, the formulation aimed to provide more sustained and predictable therapeutic action for patients with serious fibrotic conditions like IPF (ʼ150 Patent, col. 1:41-47).

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claim 27 (Compl. ¶39).
• Independent Claim 1 requires:
  • A granulate formulation of 5-methyl-1-phenyl-2-(1H)-pyridone (pirfenidone).
  • Comprising pirfenidone and pharmaceutically acceptable excipients.
  • The excipients must include an "effective amount of binder."
  • The formulation must be capable of increasing the AUC of pirfenidone by "at least 45% upon oral administration."
  • This increase is measured in comparison to "pirfenidone without excipients orally administered in a capsule shell."

U.S. Patent No. 8,778,947 - "Methods of Administering Pirfenidone Therapy"

• Patent Identification: U.S. Patent No. 8778947, "Methods of Administering Pirfenidone Therapy," issued July 15, 2014.

The Invention Explained

• Problem Addressed: The patent identifies a specific drug-drug interaction risk: pirfenidone is metabolized by the liver enzyme CYP1A2, and the common antibiotic ciprofloxacin is a moderate inhibitor of that same enzyme. Co-administration could therefore lead to a significant, and potentially unsafe, increase in a patient's exposure to pirfenidone (ʼ947 Patent, col. 1:49-54; col. 2:18-25).
• The Patented Solution: The patent claims methods for safely managing this interaction. The core of the solution is to reduce the dosage of pirfenidone by a specified amount (e.g., by about one-third to one-half) during the period when a patient is also taking a high dose of ciprofloxacin, thereby compensating for the reduced metabolic clearance of pirfenidone (ʼ947 Patent, Abstract; col. 3:20-40).
• Technical Importance: The invention provides a specific, actionable clinical guideline to mitigate the risk of adverse effects, allowing patients to be treated for bacterial infections with ciprofloxacin while continuing therapy for IPF with pirfenidone.

Key Claims at a Glance

• The complaint alleges infringement of "at least one of the claims" of the ʼ947 patent (Compl. ¶50).
• Independent Claim 1, a representative method claim, requires:
  • An improved method of administering pirfenidone therapy to treat a patient with a fibrotic, inflammatory, or autoimmune disorder.
  • The method comprises "reducing the dosage of pirfenidone... by about one-half to about one-third."
  • This dosage reduction occurs "during concomitant administration of ciprofloxacin at a dose of 750 mg twice daily (1500 mg/day)."

III. The Accused Instrumentality

Product Identification

The accused instrumentality is the generic pirfenidone product described in Torrent’s Abbreviated New Drug Application (ANDA) No. 212556 (the "Torrent ANDA Product") (Compl. ¶1, 8).

Functionality and Market Context

• The complaint alleges that the Torrent ANDA Product is a generic version of Plaintiffs’ Esbriet® tablets in 267 mg and 801 mg strengths (Compl. ¶1, 8).
• By filing an ANDA, Torrent has represented to the FDA that its product will have the same active ingredient (pirfenidone), route of administration, dosage form, and dosage strengths as Esbriet®, and that it will be bioequivalent to Esbriet® (Compl. ¶35). The product is intended for treating IPF, the same indication as Esbriet® (Compl. ¶1, 30).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

'150 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A granulate formulation of 5-methyl-1-phenyl-2-(1H)-pyridone...	The Torrent ANDA Product is alleged to be a granulate formulation of pirfenidone.	¶39	col. 11:62-63
...comprising 5-methyl-1-phenyl-2-(1H)-pyridone and pharmaceutically acceptable excipients...	The Torrent ANDA Product is alleged to contain pirfenidone and pharmaceutically acceptable excipients.	¶35, 39	col. 2:25-30
...said excipients comprising an effective amount of binder...	The Torrent ANDA Product is alleged to contain an effective amount of a binder as an excipient.	¶35, 39	col. 4:32-41
...to increase the AUC of the 5-methyl-1-phenyl-2-(1H)-pyridone at least 45% upon oral administration...	The Torrent ANDA Product is represented as being bioequivalent to Esbriet®, which the complaint alleges will satisfy this functional AUC limitation.	¶35, 39	col. 8:49-55
...as compared to pirfenidone without excipients orally administered in a capsule shell.	The infringement allegation is predicated on the Torrent ANDA Product meeting the functional limitation relative to this defined baseline.	¶39	col. 12:3-4

'947 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
An improved method of administering pirfenidone therapy...	The complaint alleges that Torrent's proposed product label will induce infringement of this method.	¶55, 56	col. 25:52-54
...comprising reducing the dosage of pirfenidone... by about one-half to about one-third...	It is alleged that Torrent’s promotional activities and package insert will instruct physicians and patients to reduce the pirfenidone dose by the claimed amount under certain conditions.	¶55	col. 3:20-35
...during concomitant administration of ciprofloxacin at a dose of 750 mg twice daily...	It is alleged that Torrent’s package insert will instruct this dose reduction specifically when the product is used concomitantly with ciprofloxacin at the specified dose.	¶55	col. 2:18-25

• Identified Points of Contention:
  • Scope Questions: For the '150 patent, a central question will be whether "bioequivalence" to Esbriet®, as required for an ANDA, is legally and factually sufficient to meet the claim's specific functional limitation of increasing AUC by "at least 45%" relative to the patent's distinct baseline (pirfenidone without excipients). For the '947 patent, the primary question is whether Torrent’s proposed product label will actually instruct a dose reduction within the claimed range, thereby inducing infringement.
  • Technical Questions: The complaint does not provide Torrent's ANDA or its proposed product label. A key evidentiary question for the '150 patent will be whether Torrent's specific formulation meets the quantitative functional test. For the '947 patent, the entire infringement theory hinges on the content of the proposed label, which is not yet in evidence. The complaint's assertion that Torrent's notice letter "does not deny" infringement of the '947 patent may suggest Torrent's Paragraph IV certification was silent on this patent, raising questions about its litigation strategy (Compl. ¶48).

V. Key Claim Terms for Construction

• The Term: "effective amount of binder to increase the AUC...at least 45%" ('150 Patent, Claim 1)

• Context and Importance: This functional limitation is the central feature distinguishing the claimed formulation from prior art. The infringement analysis for the '150 patent will depend entirely on whether the Torrent ANDA Product is shown to meet this quantitative requirement.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification lists numerous potential binders and fillers, suggesting the invention is not limited to one specific formulation (ʼ150 Patent, col. 4:32-52). A party could argue that any formulation that achieves the functional result, regardless of its exact composition, falls within the claim.
  • Evidence for a Narrower Interpretation: The patent's disclosure of an AUC increase is supported by PK data from a specific capsule formulation (ʼ150 Patent, FIG. 5-7; col. 8:28-48). A party could argue that the term "effective amount" should be construed in light of these examples and limited to formulations and binders that operate in a similar manner to what was actually tested and disclosed.

• The Term: "reducing the dosage... by about one-half to about one-third" ('947 Patent, Claim 1)

• Context and Importance: The infringement analysis for the '947 patent hinges on whether Torrent's product label will induce a dose reduction that falls within this specific numerical range. Practitioners may focus on this term because a label instructing a different reduction (e.g., "reduce dose as clinically appropriate") or simply warning of an interaction might not meet the claim's requirements for inducement.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The use of the word "about" suggests the patentee did not intend to be limited to the precise mathematical fractions of 1/3 and 1/2. The specification provides an example of reducing a 2403 mg/day dose to 1602 mg/day, a one-third reduction, which supports the range (ʼ947 Patent, col. 3:25-30).
  • Evidence for a Narrower Interpretation: A party could argue that "about" only accounts for minor rounding or measurement variability and that the claim requires a specific, substantial reduction that is recognizably within the 33.3% to 50% band. An instruction for a 25% reduction, for example, could be argued to fall outside the scope of "about one-third."

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Torrent will induce and contribute to infringement of both patents. For the '150 patent, this is based on the intended use of the product (Compl. ¶41-45). For the '947 method patent, inducement is the primary theory, based on the allegation that Torrent's "promotional activities and package inserts" will instruct users and physicians to perform the claimed method of dose reduction (Compl. ¶55-56).
• Willful Infringement: The complaint alleges willfulness based on Torrent’s pre-suit knowledge of the Asserted Patents, evidenced by its February 6, 2019 notice letter (Compl. ¶33, 58). It further alleges that Torrent’s actions were undertaken "without a good faith belief that they are not infringing," and seeks a finding that the case is exceptional (Compl. ¶58).

VII. Analyst’s Conclusion: Key Questions for the Case

• A key evidentiary question will be one of functional performance: For the '150 patent, will discovery reveal that Torrent's proposed generic formulation, while bioequivalent to the brand-name drug, also meets the distinct and quantitative functional requirement of increasing drug exposure (AUC) by "at least 45%" when measured against the patent's specific no-excipient baseline?
• A core issue will be one of inducement: For the '947 patent, does Torrent's proposed product label—once disclosed—contain explicit instructions that would lead physicians and patients to reduce the pirfenidone dosage by the specific "about one-half to about one-third" fraction claimed in the patent when co-administered with ciprofloxacin, or does it provide a non-infringing alternative?
• A final question relates to litigation posture: What is the significance of the complaint's allegation that Torrent's notice letter "does not deny" that its product will infringe the '947 patent, and how will this affect arguments regarding infringement and willfulness as the case proceeds?