DCT
1:17-cv-01293
Eli Lilly Co v. Eagle Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Eli Lilly and Company (Indiana)
- Defendant: Eagle Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:17-cv-01293, D. Del., 09/11/2017
- Venue Allegations: Plaintiff asserts that venue is proper in the District of Delaware because Defendant is a Delaware corporation. The complaint notes that Defendant itself previously argued in a related matter that its state of incorporation is the proper basis for patent venue.
- Core Dispute: Plaintiff alleges that Defendant’s submission of a New Drug Application (NDA) for a pemetrexed injection product constitutes an act of infringement of a patent covering a method of administering pemetrexed in combination with vitamin supplementation to reduce toxicity.
- Technical Context: The technology concerns a combination chemotherapy method designed to improve the safety profile of antifolate cancer drugs by mitigating their severe side effects.
- Key Procedural History: The complaint states this action was filed after Plaintiff received a Paragraph IV notice letter regarding Defendant's NDA. It also follows a nearly identical lawsuit filed by Plaintiff against Defendant in the Southern District of Indiana, which Defendant moved to dismiss for improper venue. The complaint notes this action is being filed in Delaware to "avoid a needless dispute" over the venue issue. Subsequent to the filing of this complaint, the patent-in-suit was the subject of multiple Inter Partes Review (IPR) proceedings at the U.S. Patent and Trademark Office, which concluded with a certificate confirming the patentability of all challenged claims.
Case Timeline
| Date | Event |
|---|---|
| 2000-06-30 | '209 Patent Priority Date |
| 2010-08-10 | '209 Patent Issue Date |
| 2017-08-07 | Date of Eagle's Notice Letter to Lilly |
| 2017-08-14 | Prior related lawsuit filed in S.D. Indiana |
| 2017-09-08 | Eagle moves to dismiss S.D. Indiana case for improper venue |
| 2017-09-11 | Complaint Filing Date (D. Del.) |
| 2019-09-26 | IPR Certificate issued confirming patentability of claims |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,772,209 - "Antifolate Combination Therapies"
- Patent Identification: U.S. Patent No. 7,772,209, "Antifolate Combination Therapies", issued August 10, 2010.
The Invention Explained
- Problem Addressed: Antifolate drugs, a class of chemotherapeutic agents, are effective against cancer but are associated with "potentially, life-threatening toxicity" that limits their optimal use (’209 Patent, col. 2:11-12). This toxicity includes severe side effects such as skin rashes, fatigue, and mortality (’209 Patent, col. 2:33-36).
- The Patented Solution: The patent describes the "surprising and unexpected" discovery that administering an antifolate drug in combination with a "methylmalonic acid lowering agent," such as vitamin B12, can "significantly" reduce these toxic effects "without adversely affecting therapeutic efficacy" (’209 Patent, col. 2:32-38). The patent further discloses that adding folic acid to this regimen "synergistically reduces the toxic events associated with the administration of antifolate drugs" (’209 Patent, col. 2:47-50). The invention is therefore a method for more safely administering antifolates like pemetrexed.
- Technical Importance: This method provided a way to improve the therapeutic window of an important class of cancer drugs, potentially allowing for more effective treatment regimens with fewer harmful side effects for patients (’209 Patent, col. 2:26-32).
Key Claims at a Glance
- The complaint asserts claims 1-22 (Compl. ¶27). The asserted independent claims are claims 1 and 12.
- Independent Claim 1 recites a method with the following essential elements:
- A method for administering pemetrexed disodium to a patient, comprising:
- administering an effective amount of folic acid;
- administering an effective amount of a methylmalonic acid lowering agent (selected from a specified list including vitamin B12);
- followed by administering an effective amount of pemetrexed disodium.
- Independent Claim 12 recites an "improved method" with the following essential elements:
- An improved method for administering pemetrexed disodium, wherein the improvement comprises:
- administration of between about 350 µg and 1000 µg of folic acid prior to the first administration of pemetrexed disodium;
- administration of about 500 µg to 1500 µg of vitamin B12 prior to the first administration of pemetrexed disodium; and
- administration of pemetrexed disodium.
III. The Accused Instrumentality
Product Identification
The accused instrumentality is "Eagle's NDA Product," identified as "Pemetrexed Injection, 25mg/mL, 500 mg vial product" for which Eagle submitted NDA No. 209472 to the FDA (Compl. ¶1).
Functionality and Market Context
The product is a drug containing pemetrexed disodium or its equivalent, which is an antifolate chemotherapy agent (Compl. ¶1, ¶25). The infringement allegation is based on the intended use of this product. The complaint alleges that "the proposed labeling for Eagle's NDA Product involves administration of folic acid and vitamins B12" (Compl. ¶26). The product is positioned as a competitor to Plaintiff's ALIMTA® product, which is used for treating various cancers (Compl. ¶1). The complaint cites Eagle's SEC filings to allege that the product targets a market representing "$3.4 billion in U.S. peak branded drug sales" (Compl. ¶10). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges that the use of Eagle's product as directed by its proposed labeling will infringe claims 1-22 of the ’209 patent (Compl. ¶27). The allegations for the more specific independent claim 12 are summarized below.
’209 Patent Infringement Allegations
| Claim Element (from Independent Claim 12) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a) administration of between about 350 µg and about 1000 µg of folic acid prior to the first administration of pemetrexed disodium; | The proposed labeling for Eagle's NDA Product allegedly directs the administration of folic acid in conjunction with its drug. | ¶26, ¶27 | col. 11:34-38 |
| b) administration of about 500 µg to about 1500 µg of vitamin B12, prior to the first administration of pemetrexed disodium; and | The proposed labeling for Eagle's NDA Product allegedly directs the administration of vitamin B12 in conjunction with its drug. | ¶26, ¶27 | col. 12:1-4 |
| c) administration of pemetrexed disodium. | Eagle's NDA Product contains pemetrexed disodium or its equivalent. | ¶25, ¶27 | col. 12:5 |
- Identified Points of Contention:
- Scope Questions: The complaint does not provide the specific dosage and timing information from Eagle's proposed label. A primary question for the court will be one of factual comparison: do the specific instructions in Eagle's label for administering folic acid and vitamin B12 fall within the numerical ranges and temporal limitations (e.g., "prior to") required by the patent's claims?
- Technical Questions: The infringement theory relies on inducement. A key evidentiary question will be whether Eagle's proposed label does more than merely mention vitamin supplementation, and instead actively instructs or encourages physicians and patients to perform all steps of the claimed method in the manner required by the claims.
V. Key Claim Terms for Construction
The Term: "an effective amount" (from Claim 1)
Context and Importance: This term appears three times in claim 1, defining the required dose for folic acid, the vitamin B12 agent, and pemetrexed. The dispute will likely center on whether the dosages specified in Eagle's proposed label constitute an "effective amount" for the claimed purposes (i.e., toxicity reduction for the vitamins and therapeutic effect for the pemetrexed). Practitioners may focus on this term as its construction will determine the breadth of the claim.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a functional definition: "an amount of a compound or drug, which is capable of performing the intended result" (’209 Patent, col. 4:52-54). This language may support a broader construction not strictly tied to specific numerical values.
- Evidence for a Narrower Interpretation: The patent discloses specific dosage ranges and clinical trial data (e.g., "about 0.1 mg to about 30 mg" of folic acid and Table 1) (’209 Patent, col. 6:36-37, col. 10). This may support an argument that "effective amount" should be construed more narrowly in light of these specific examples.
The Term: "prior to" (from Claims 1 and 12)
Context and Importance: The temporal relationship between the administration of the vitamins and the pemetrexed is a critical claim limitation. The definition of "prior to" will be central to determining whether the administration schedule on Eagle's proposed label meets this requirement.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term is not explicitly defined, which may support giving it a plain and ordinary meaning that encompasses any administration of vitamins that occurs before the pemetrexed, regardless of the time interval.
- Evidence for a Narrower Interpretation: The specification provides several concrete examples of time intervals, such as "from about 1 to about 24 hours prior" for folic acid and "1 to 3 weeks prior" for vitamin B12 (’209 Patent, col. 6:26-27, 6:40-41). This may support a narrower construction that limits the scope of "prior to" to timeframes consistent with these embodiments.
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement, stating that Eagle "plans and intends to, and will, actively induce infringement" through its proposed labeling, which will instruct users to perform the patented method (Compl. ¶33). It also pleads contributory infringement, alleging that Eagle’s product is "especially made or adapted for use in infringing" the patent and is "not suitable for substantial noninfringing use" (Compl. ¶34).
- Willful Infringement: The complaint alleges that Eagle has "knowledge of the claims of the '209 patent" yet has "continued to assert its intent to engage in" the accused activities (Compl. ¶32). This allegation appears to be based on knowledge obtained at least as of the filing of its NDA and the associated Paragraph IV certification.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of infringement by labeling: does the specific text of Eagle's proposed product label direct medical professionals to administer folic acid, vitamin B12, and pemetrexed according to a regimen that falls within the dosage and timing parameters of the asserted patent claims? The outcome will depend on a direct comparison between the proposed label and the claim language.
- A key strategic question will concern the resilience of the patent's validity. While the complaint alleges infringement, Eagle's Paragraph IV certification signals an intent to challenge the patent's validity (Compl. ¶28). The core of the case may therefore turn on whether Eagle can succeed with invalidity arguments, particularly given that claims 1-22 of the '209 patent have previously survived multiple Inter Partes Review challenges at the U.S. Patent and Trademark Office.