DCT
1:14-cv-00757
Vanda Pharma Inc v. Roxane Laboratories Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Vanda Pharmaceuticals Inc. (Delaware)
- Defendant: Roxane Laboratories, Inc. (Nevada)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Paul, Weiss, Rifkind, Wharton & Garrison LLP
- Case Identification: 1:14-cv-00757, D. Del., 06/16/2014
- Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendant conducts substantial business in the state, derives revenue from the state, and has previously availed itself of the forum to litigate other patent disputes.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of the schizophrenia drug FANAPT® (iloperidone) constitutes an act of infringement of a patent directed to a method of administering the drug based on a patient's genetic profile.
- Technical Context: The technology at issue is in the field of pharmacogenomics, where genetic testing is used to personalize drug therapy, specifically by adjusting the dosage of the antipsychotic drug iloperidone to mitigate the risk of cardiac side effects in genetically susceptible patients.
- Key Procedural History: This is a Hatch-Waxman action triggered by Defendant’s ANDA filing seeking to market a generic drug prior to patent expiration. The complaint notes that Defendant sent Plaintiff’s predecessor-in-interest a notice letter regarding its ANDA filing on October 17, 2013.
Case Timeline
| Date | Event |
|---|---|
| 2004-09-30 | '610 Patent Priority Date |
| 2009-05-06 | FDA approves Vanda's FANAPT® New Drug Application |
| 2013-10-17 | Roxane sends Notice Letter regarding ANDA filing |
| 2013-11-19 | '610 Patent Issued |
| 2014-06-16 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,586,610 - "Methods for the Administration of Iloperidone"
- Patent Identification: U.S. Patent No. 8,586,610, "Methods for the Administration of Iloperidone," issued November 19, 2013. (Compl. ¶14; ’610 Patent, front page).
The Invention Explained
- Problem Addressed: The patent describes that certain individuals possess genetic variations (polymorphisms) in the CYP2D6 gene, which makes them "poor metabolizers" of certain drugs, including the antipsychotic iloperidone. (Compl. ¶15; ’610 Patent, col. 3:21-28). This impaired metabolism can lead to higher-than-normal drug concentrations in the body, which is associated with a dangerous side effect known as QTc prolongation—an abnormality in the heart's electrical cycle that can lead to serious arrhythmias. (Compl. ¶15; ’610 Patent, col. 3:49-53).
- The Patented Solution: The invention provides a method for administering iloperidone more safely by tailoring the dosage to a patient's genetic makeup. The method involves first performing a "genotyping assay" to determine if a patient has a "CYP2D6 poor metabolizer genotype." (’610 Patent, col. 17:5-11). If the patient is identified as a poor metabolizer, they are administered a reduced dose of iloperidone (12 mg/day or less). If they are a normal metabolizer, they receive a standard, higher dose (greater than 12 mg/day, up to 24 mg/day). (’610 Patent, col. 17:12-20). This dose-adjustment strategy is designed to lower the risk of QTc prolongation in the susceptible patient subpopulation. (’610 Patent, col. 17:21-24).
- Technical Importance: The claimed method exemplifies a personalized medicine approach, using a patient’s genetic information to customize treatment and improve the safety profile of a pharmaceutical drug. (’610 Patent, col. 3:54-4:14).
Key Claims at a Glance
- The complaint asserts "one or more claims" of the ’610 patent. (Compl. ¶3). The foundational independent method claim is Claim 1.
- The essential elements of independent Claim 1 are:
- A method for treating a patient with iloperidone for schizophrenia.
- Determining if the patient is a "CYP2D6 poor metabolizer" by performing a "genotyping assay" on a biological sample to identify a "CYP2D6 poor metabolizer genotype."
- If the patient has the poor metabolizer genotype, internally administering iloperidone in an amount of 12 mg/day or less.
- If the patient does not have the poor metabolizer genotype, internally administering iloperidone in an amount greater than 12 mg/day, up to 24 mg/day.
- Wherein the risk of QTc prolongation for the poor metabolizer patient is lower with the reduced dose than it would be with the standard dose.
III. The Accused Instrumentality
Product Identification
- The complaint identifies Defendant's generic iloperidone oral tablets (1 mg, 2 mg, 4 mg, 6 mg, 8mg, 10 mg, and 12 mg strengths) as the product that would infringe upon commercialization. (Compl. ¶4). The act of infringement alleged under 35 U.S.C. § 271(e)(2)(A) is Defendant's filing of an Abbreviated New Drug Application (ANDA) with the FDA to obtain approval for this generic product. (Compl. ¶5).
Functionality and Market Context
- The infringement theory is not based on the function of the drug itself, but on the instructions for its use that will be included in the proposed product labeling. (Compl. ¶¶ 17, 22). The complaint alleges that Defendant’s ANDA "essentially copies the FANAPT® Label," which instructs physicians to perform the steps of the patented method. (Compl. ¶22).
- Specifically, the label is alleged to instruct physicians to first "determine whether the patient is a poor CYP2D6 metabolizer using available laboratory tests," and then to "administer either the target dose if the patient is a normal CYP2D6 metabolizer or a halved dosage if the patient is a poor CYP2D6 metabolizer." (Compl. ¶17). These alleged instructions form the basis for the claim of induced infringement.
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’610 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating a patient with iloperidone, wherein the patient is suffering from schizophrenia... | Defendant's ANDA seeks approval to market generic iloperidone tablets for the treatment of schizophrenia. | ¶4 | col. 17:1-4 |
| determining whether the patient is a CYP2D6 poor metabolizer by... performing or having performed a genotyping assay on the biological sample to determine if the patient has a CYP2D6 poor metabolizer genotype... | Defendant's proposed label allegedly instructs physicians to determine if a patient is a poor CYP2D6 metabolizer using available laboratory tests, which Plaintiff alleges constitutes the claimed genotyping step. | ¶17, ¶22 | col. 17:5-11 |
| if the patient has a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount of 12 mg/day or less... | Defendant's proposed label allegedly instructs physicians to administer a "halved dosage" to patients identified as poor metabolizers, which corresponds to the claimed lower dosage range. | ¶17, ¶22 | col. 17:12-15 |
| and if the patient does not have a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount that is greater than 12 mg/day, up to 24 mg/day... | Defendant's proposed label allegedly instructs physicians to administer the "target dose" to patients identified as normal metabolizers, which corresponds to the claimed higher dosage range. | ¶17, ¶22 | col. 17:16-20 |
Identified Points of Contention
- Scope Questions: The case is one of induced infringement, where the central question is whether Defendant's proposed product label would cause physicians to directly infringe the method claims. A key dispute may arise over whether the label's language is sufficiently specific to meet the legal standard for inducement, which requires showing that the accused infringer knew of the patent and specifically intended for the infringing acts to occur.
- Technical Questions: A potential technical question is whether the "available laboratory tests" allegedly referenced on the proposed label (Compl. ¶17) are necessarily the "genotyping assay" required by Claim 1, or if they could encompass other non-infringing tests (e.g., phenotyping). Further, a factual question may arise as to whether the "halved dosage" for poor metabolizers will, in all clinical scenarios, result in a dose that is "12 mg/day or less" as claimed.
V. Key Claim Terms for Construction
The Term: "CYP2D6 poor metabolizer genotype"
- Context and Importance: This term is the central diagnostic criterion that triggers the claimed dose adjustment. The definition of this term is critical because it dictates which specific genetic markers the accused product label must instruct physicians to test for. Practitioners may focus on this term because its scope will determine whether the label's instructions map onto the claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim language itself is functional, referring to a "genotype" that results in a "poor metabolizer" status, without listing specific mutations. This may support a construction covering any genotype known to cause a poor metabolizer phenotype. (’610 Patent, col. 17:10-11).
- Evidence for a Narrower Interpretation: The patent specification focuses heavily on two specific polymorphisms, CYP2D6G1846A and CYP2D6C100T, as primary examples. (’610 Patent, col. 5:7-21). A defendant could argue that the term should be limited to the specific genotypes that the inventors actually identified and studied, as described in the patent's detailed description and tables. (’610 Patent, Table 1A-1B).
The Term: "genotyping assay"
- Context and Importance: This term defines the specific type of diagnostic action required by the claim. The infringement analysis depends on whether the accused label instructs the use of this specific type of assay. If the label is interpreted as permitting or encouraging alternative, non-genotyping tests (e.g., measuring drug metabolite levels in the blood), it could provide a basis for a non-infringement argument.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent describes multiple methods for identifying polymorphisms, including sequencing, amplification, and various probe-based assays, suggesting the term is not limited to a single technique. (’610 Patent, col. 11:25-col. 12:44).
- Evidence for a Narrower Interpretation: The patent provides specific examples of assays used, such as a "triplex PCR strategy" and the "Invader® assay." (’610 Patent, col. 5:36-66). A party might argue that the term should be understood in the context of these specific examples of direct DNA-based testing, as distinguished from indirect phenotyping methods.
VI. Other Allegations
- Indirect Infringement: The complaint’s core allegation is inducement of infringement. It alleges that Defendant, by filing an ANDA with a proposed label that instructs physicians on how to use generic iloperidone, will intentionally encourage and cause physicians to perform the patented method. (Compl. ¶¶ 22, 24). The complaint alleges Defendant's knowledge of the patent is established by its notice letter of October 17, 2013, and the filing of this lawsuit. (Compl. ¶21).
- Willful Infringement: The complaint does not contain an explicit allegation of willful infringement or a prayer for enhanced damages.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of induced infringement: does the specific language of Defendant’s proposed product label, which is not included in the complaint, provide sufficiently clear and explicit instructions to establish that Defendant possessed the specific intent to encourage physicians to perform every step of the claimed method?
- The outcome may depend on definitional scope: can the term "CYP2D6 poor metabolizer genotype" be construed broadly to cover any genetic variant that results in the poor metabolizer phenotype, or will it be limited to the specific alleles and mutations explicitly detailed in the patent’s specification?
- A key evidentiary question will be one of factual correspondence: does the "halved dosage" for poor metabolizers, as instructed on the accused label, fall within the "12 mg/day or less" limitation of Claim 1 across all standard "target doses," and do the "available laboratory tests" referenced on the label exclusively or necessarily equate to the "genotyping assay" required by the claim?