DCT
2:13-cv-08567
Los Angeles Biomedical Research Institute At Harbor UCLA Medical Center v. Eli Lilly Co
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (California)
- Defendant: Eli Lilly and Company and Lilly USA, LLC (Indiana)
- Plaintiff’s Counsel: Fenwick & West LLP
- Case Identification: 2:13-cv-08567, C.D. Cal., 11/20/2013
- Venue Allegations: Plaintiff alleges venue is proper because a substantial part of the events giving rise to the claims occurred in the district, Defendant conducts business in California, and Defendant has induced acts of infringement in the district.
- Core Dispute: Plaintiff alleges that Defendant’s administration instructions for its Cialis® product for once-daily use infringes a patent directed to methods of treating penile fibrosis via the long-term, continuous administration of a PDE-5 inhibitor.
- Technical Context: The technology concerns pharmaceutical methods for treating underlying fibrotic causes of conditions like Peyronie's disease and erectile dysfunction, a commercially significant market.
- Key Procedural History: The complaint alleges that Plaintiff provided Defendant with notice of the patent-in-suit and its infringement theory in February 2013 and again in May 2013, several months prior to filing the lawsuit.
Case Timeline
| Date | Event |
|---|---|
| 2002-10-22 | ’903 Patent Priority Date (Provisional Application 60/420,281 Filing) |
| 2003-11-01 | Cialis® first receives FDA approval for as-needed use |
| 2008-01-01 | Cialis® receives FDA approval for once-daily use |
| 2012-03-13 | U.S. Patent No. 8,133,903 Issues |
| 2013-11-20 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
- Patent Identification: U.S. Patent No. 8133903, Methods of Use of Inhibitors of Phosphodiesterases and Modulators of Nitric Oxide-Reactive Oxygen Species, and Metalloproteinases in the Treatment of Peyronie’s Disease, Arteriosclerosis and Other Fibrotic Diseases, issued March 13, 2012.
- The Invention Explained:
- Problem Addressed: The patent describes fibrotic diseases, such as Peyronie’s disease and arteriosclerosis, which are characterized by excessive collagen deposition and can lead to conditions like penile deformation and erectile dysfunction (ED). The background notes a need for effective non-surgical treatments for these conditions (’903 Patent, col. 1:29-33, col. 2:5-8).
- The Patented Solution: The invention is a method for treating fibrotic conditions by administering agents that modulate the underlying cellular processes. Specifically, it proposes using phosphodiesterase (PDE) inhibitors, such as PDE-5 inhibitors, to increase levels of cyclic guanosine monophosphate (cGMP). This is claimed to arrest or reduce collagen synthesis and induce apoptosis in the myofibroblast cells responsible for the fibrosis, thereby treating the underlying cause of the condition (’903 Patent, Abstract; col. 2:50-62).
- Technical Importance: The claimed method provides a pharmacological approach aimed at reversing or arresting the pathological tissue changes (fibrosis) that cause certain forms of ED, rather than solely addressing its symptoms (’903 Patent, col. 2:41-48).
- Key Claims at a Glance:
- The complaint’s allegations focus on the elements of independent claim 1.
- Independent Claim 1, as corrected, recites:
- A method comprising: administering a PDE-5 inhibitor according to a continuous long-term regimen;
- to an individual with penile tunical fibrosis and/or corporal tunical fibrosis;
- thereby arresting or regressing said fibrosis;
- wherein the inhibitor is administered at a dosage up to 1.5 mg/kg/day for not less than 45 days.
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is the method of using the pharmaceutical drug tadalafil, marketed as Cialis®, when prescribed according to its "once daily use" label (Compl. ¶14, ¶16).
- Functionality and Market Context: Tadalafil is a phosphodiesterase-5 (PDE-5) inhibitor (Compl. ¶14). In January 2008, Defendant obtained FDA approval to market Cialis® for "once daily use" for the treatment of erectile dysfunction (ED), with recommended doses of 2.5 mg or 5 mg (Compl. ¶16). The complaint alleges that a significant percentage of patients with ED suffer from underlying fibrotic conditions such as corporal veno-occlusive dysfunction (CVOD) or Peyronie’s disease (PD) (Compl. ¶10, ¶17). The complaint notes that Cialis® is a major commercial product, with 2012 worldwide revenues of nearly $1.93 billion (Compl. ¶19).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’903 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method comprising: administering a cyclic guanosine 3', 5'-monophosphate (cGMP) type 5 phosphodiesterase (PDE 5) inhibitor according to a continuous long-term regimen | Defendant instructs physicians to prescribe Cialis® (tadalafil), a PDE-5 inhibitor, for "once daily use," which the complaint alleges constitutes a continuous long-term regimen. | ¶14, ¶16, ¶24 | col. 64:5-15 |
| to an individual with at least one of a penile tunical fibrosis and corporal tunical fibrosis | Cialis® is administered to patients with erectile dysfunction (ED), a condition the complaint alleges is frequently caused by underlying penile fibrosis (CVOD or PD). | ¶10, ¶17, ¶23 | col. 1:29-33 |
| and arresting or regressing the at least one of the penile tunical fibrosis and corporal tunical fibrosis | The complaint alleges Defendant knew or expected that the once-daily administration of Cialis® would treat the underlying penile fibrosis, thereby causing its arrest or regression. | ¶17, ¶23 | col. 2:55-58 |
| wherein the PDE-5 inhibitor is administered at a dosage up to 1.5 mg/kg/day for not less than 45 days. | The Cialis® label instructs a 2.5 mg or 5 mg daily dose, which is alleged to be below the 1.5 mg/kg/day threshold, as part of a continuous regimen lasting 45 days or more. | ¶16, ¶23 | col. 64:7-10 |
- Identified Points of Contention:
- Scope Questions: Does treating the general population of patients with the symptom of ED meet the claim limitation of administering the drug "to an individual with... penile tunical fibrosis"? A central issue may be whether the plaintiff can prove that the group of patients receiving "once daily" Cialis® is coextensive with, or substantially overlaps with, the patient group defined in the claim.
- Technical Questions: What evidence does the complaint provide that the accused method actually causes the "arrest or regression" of fibrosis in patients, as required by the claim? The complaint alleges Defendant's knowledge and expectation of this outcome (Compl. ¶17), but demonstrating that this functional result occurs as part of the infringing act will be a key evidentiary question.
V. Key Claim Terms for Construction
The Term: "continuous long-term regimen"
- Context and Importance: This term is critical for distinguishing the accused "once daily use" from the prior art "as-needed" use of PDE-5 inhibitors. The definition will determine whether simply taking a pill every day, regardless of the duration prescribed or followed by the patient, meets this limitation.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim language itself provides a temporal floor, defining "long-term" as "not less than 45 days." The patent specification discusses reversing or preventing the "further development of the fibrosis," which suggests a sustained, ongoing treatment is contemplated (’903 Patent, col. 3:9-14).
- Evidence for a Narrower Interpretation: The patent describes its method as a treatment for the fibrotic condition itself (’903 Patent, Abstract). A defendant may argue that a "regimen" must be one prescribed specifically for fibrosis, not for the symptom of ED. The examples showing a fixed 45-day treatment period in rat models could be cited to argue for a more structured or finite meaning than indefinite daily use (’903 Patent, col. 56:20-22).
The Term: "an individual with at least one of a penile tunical fibrosis and corporal tunical fibrosis"
- Context and Importance: Infringement depends on whether the patients receiving "once daily" Cialis® for ED are considered to have the specific conditions recited in the claim. The complaint equates this with conditions like CVOD and PD (Compl. ¶10).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent title and abstract refer to a range of "Fibrotic Diseases," suggesting the terms should be construed broadly. The background links ED to an "increase in collagen fibers" in the penis, which is a general description of fibrosis (’903 Patent, col. 2:26-29).
- Evidence for a Narrower Interpretation: A defendant may argue that these terms are not met by a general diagnosis of ED, which can have multiple non-fibrotic causes, but instead require a specific clinical diagnosis of a fibrotic pathology like Peyronie's disease. The patent's "Description of Related Art" section focuses heavily on Peyronie's disease as the primary example of this pathology (’903 Patent, col. 1:29-41).
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b) (Compl. ¶24). It asserts that Defendant, with knowledge of the ’903 patent, actively induces and encourages infringement by instructing physicians—through the Cialis® prescription label—to prescribe the drug for "once daily use" in a manner that directly infringes the patent's claims.
- Willful Infringement: The complaint alleges willful infringement based on both pre- and post-issuance knowledge of the ’903 patent (Compl. ¶25). Pre-suit knowledge is alleged based on Defendant's general monitoring of patents and publications in the field (Compl. ¶22). The complaint further alleges specific knowledge as of February 2013 and May 2013, when Plaintiff sent notice letters to Defendant identifying the patent and the infringing conduct (Compl. ¶21).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central question will be one of infringement nexus: can the plaintiff demonstrate that administering Cialis® for the labeled indication of erectile dysfunction (ED) constitutes infringement of a method claim requiring treatment of individuals with specific underlying fibrotic conditions, or is there a legally significant mismatch between the indicated patient population and the claimed patient population?
- A core issue for the inducement claim will be one of specific intent: does instructing physicians to prescribe a drug for a labeled symptom (ED) demonstrate the requisite intent to encourage the performance of an unstated, patented method of treating an underlying pathology (arresting fibrosis), especially when the infringing acts are performed by third-party physicians and patients?