DCT
1:10-cv-01376
Eli Lilly Co v. Teva Parenteral Medicines Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Eli Lilly and Company (Indiana)
- Defendant: Teva Parenteral Medicines, Inc. (Delaware); APP Pharmaceuticals, LLC (Delaware); Pliva Hrvatska d.o.o. (Croatia); Teva Pharmaceuticals USA, Inc. (Delaware); and Barr Laboratories, Inc. (Delaware)
- Plaintiff’s Counsel: Barnes & Thornburg LLP; Williams & Connolly LLP
- Case Identification: 1:10-cv-01376, S.D. Ind., 10/29/2010
- Venue Allegations: Venue is asserted as proper in the Southern District of Indiana based on defendants' alleged marketing, sales, and distribution of generic drugs throughout the United States, including within the state of Indiana, constituting systematic and continuous business contacts.
- Core Dispute: Plaintiff alleges that Defendants' filing of Abbreviated New Drug Applications (ANDAs) to market generic versions of the chemotherapy drug ALIMTA® constitutes an act of infringement of a patent covering a method of administering the drug in combination with vitamin B12 and folic acid to reduce toxicity.
- Technical Context: The lawsuit concerns the field of oncology therapeutics, specifically methods for improving the safety profile of antifolate chemotherapy agents, which are a critical but often toxic class of cancer-fighting drugs.
- Key Procedural History: The action arises under the Hatch-Waxman Act, triggered by Defendants notifying Plaintiff of their ANDA filings, which included certifications under 21 U.S.C. § 355(j)(2)(A)(vii)(IV) (a "Paragraph IV certification") asserting that the patent-in-suit is invalid, unenforceable, or will not be infringed by their proposed generic products.
Case Timeline
| Date | Event |
|---|---|
| 2000-06-30 | '209 Patent Priority Date (Earliest Provisional Filing) |
| 2008-04-24 | Teva sends notice letter for ANDA No. 90-352 (500 mg) |
| 2008-06-10 | APP sends notice letter for ANDA No. 90-384 (500 mg) |
| 2008-10-14 | Teva sends notice letter for ANDA No. 90-674 (100 mg) |
| 2009-03-19 | Barr sends notice letter for ANDA No. 91-111 |
| 2010-08-10 | U.S. Patent No. 7,772,209 Issues |
| 2010-09-16 | Pliva sends notice letter for ANDA No. 091111 |
| 2010-09-17 | Teva sends new notice letters regarding the '209 Patent |
| 2010-10-29 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,772,209 - Novel Antifolate Combination Therapies
- Patent Identification: U.S. Patent No. 7772209, issued August 10, 2010.
The Invention Explained
- Problem Addressed: The patent describes that antifolate drugs, a class of antineoplastic agents, are limited by "potentially, life-threatening toxicity" that can manifest as severe myelosuppression and gastrointestinal issues, complicating their clinical development and use (’209 Patent, col. 1:61-66, col. 2:11-14).
- The Patented Solution: The invention is a method to improve the therapeutic utility of antifolates by reducing these toxic side effects. The inventors discovered that administering a "methylmalonic acid lowering agent," such as vitamin B12, in combination with the antifolate drug significantly reduces toxic events like mortality and skin rashes without compromising the drug's anti-tumor efficacy (’209 Patent, col. 2:31-38). The method may also include co-administration of a "FBP binding agent" like folic acid, which is alleged to synergistically reduce toxicity (’209 Patent, col. 2:47-54).
- Technical Importance: This method provides a way to make a potent class of cancer drugs safer for patients, potentially allowing for more effective dosing regimens and broader clinical application (’209 Patent, col. 2:38-40).
Key Claims at a Glance
- The complaint alleges infringement of "one or more claims" of the ’209 patent (Compl. ¶29). Independent claim 12 is representative of the core inventive method.
- Independent Claim 12 elements:
- An improved method for administering pemetrexed disodium to a patient in need of chemotherapeutic treatment,
- wherein the improvement comprises:
- a) administration of between about 350 µg and about 1000 µg of folic acid prior to the first administration of pemetrexed disodium;
- b) administration of about 500 µg to about 1500 µg of vitamin B12, prior to the first administration of pemetrexed disodium; and
- c) administration of pemetrexed disodium.
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are the Defendants' proposed generic versions of ALIMTA®, identified as Pemetrexed Disodium for Injection in various dosages (Compl. ¶¶23, 40, 57, 72). The act of infringement is the filing of ANDAs (Nos. 90-352, 90-674, 90-384, and 91-111/091111) seeking FDA approval to market these products (Compl. ¶1).
Functionality and Market Context
- The defendants' products are generic formulations of the active ingredient pemetrexed disodium, intended for use as a chemotherapy agent (Compl. ¶¶25, 42, 59, 74). The infringement allegations are based on the proposed use of these products. The complaint alleges that the proposed labeling for the generic products will instruct medical professionals to administer the drug in a manner that includes co-administration of folic acid and vitamin B12, thereby practicing the patented method (Compl. ¶¶26, 43, 60, 75). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’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 use of Defendants' ANDA products, as directed by their proposed labeling, involves the administration of folic acid. | ¶¶26, 43, 60, 75, 84 | col. 11:35-39 |
| b) administration of about 500 µg to about 1500 µg of vitamin B12, prior to the first administration of pemetrexed disodium; and | The use of Defendants' ANDA products, as directed by their proposed labeling, involves the administration of vitamin B12. | ¶¶26, 43, 60, 75, 84 | col. 11:40-44 |
| c) administration of pemetrexed disodium. | Defendants' ANDA products contain pemetrexed disodium. | ¶¶25, 42, 59, 74, 83 | col. 11:45-46 |
- Identified Points of Contention:
- Technical Questions: A primary factual dispute will concern the specific instructions in the Defendants' proposed product labels, which are not detailed in the complaint. The key question is whether those labels direct or recommend the administration of folic acid and vitamin B12 within the dosage ranges and, critically, "prior to the first administration of pemetrexed disodium" as required by the claim.
- Scope Questions: As this is a method claim and Defendants are drug manufacturers, the case rests on a theory of indirect infringement. A central question will be whether the act of selling a drug with a particular label constitutes inducement, which requires evidence that the Defendants specifically intended for physicians to perform the patented method.
V. Key Claim Terms for Construction
The Term: "prior to the first administration of pemetrexed disodium"
Context and Importance: This timing limitation is a cornerstone of the asserted claim, which recites a pretreatment regimen. The infringement analysis will depend entirely on whether the instructions on the accused labels direct this specific sequence. Practitioners may focus on this term to determine if a label that, for example, merely notes the possibility of vitamin supplementation without mandating its timing infringes.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discusses various administration protocols. A party might argue that "prior to" simply means any time before, without a specific required interval, pointing to general language about pretreatment (’209 Patent, col. 6:23-27).
- Evidence for a Narrower Interpretation: The specification describes a clinical study protocol where vitamin B12 was injected "1-3 weeks prior to treatment" and folic acid was started "approximately 1 to 3 weeks before treatment" (’209 Patent, col. 9:20-27). A party could argue this embodiment limits "prior to" to a specific, multi-week pretreatment window, potentially narrowing the claim scope to exclude less specific instructions.
The Term: "administering pemetrexed disodium"
Context and Importance: This term defines the active chemotherapeutic step. While the compound itself is not in dispute, its specific form as a "disodium" salt is part of the claim. A dispute could arise if a generic product were to use a different salt or formulation of pemetrexed.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party could argue that "pemetrexed disodium" is representative of the broader class of pemetrexed antifolates and that the core invention is the vitamin co-administration method, not the specific salt form.
- Evidence for a Narrower Interpretation: The specification repeatedly and specifically identifies the compound as "pemetrexed disodium (Alimta®, Eli Lilly and Company...)" (’209 Patent, col. 1:58-60). A defendant could argue this linkage expressly limits the claim to the exact disodium salt used in the brand-name product.
VI. Other Allegations
- Indirect Infringement: The complaint's primary theory is indirect infringement. Active inducement is alleged based on the claim that Defendants' proposed product labels will direct and instruct physicians and patients to use the generic products in a manner that practices the patented method (Compl. ¶¶33, 50, 65, 89). Knowledge and intent are alleged to be established by Defendants' notice letters and Paragraph IV certifications (Compl. ¶¶32, 49, 64, 88). Contributory infringement is also pled, with allegations that the proposed products are "especially made or adapted for use in infringing" the patent and are not suitable for a substantial noninfringing use (Compl. ¶¶34, 51, 66, 90).
- Willful Infringement: While not using the word "willful," the complaint alleges that each defendant "is without a reasonable basis for believing that it will not be liable for infringing the '209 patent" (Compl. ¶¶36, 53, 68, 92). This allegation, combined with the assertion of pre-suit knowledge via the ANDA notice letters, forms the basis for a potential claim for enhanced damages.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: What are the precise instructions contained within the Defendants' proposed generic drug labels? The outcome will likely depend on whether the language on those labels is found to direct physicians to administer vitamin B12 and folic acid in the specific sequence and dosages required by the asserted claims.
- A key legal question will be one of inducement: Assuming the labels describe the patented method, does the language rise to the level of actively encouraging or promoting the infringing use, thereby establishing the specific intent required to find a drug manufacturer liable for inducing infringement of a method claim?
- The case may also turn on a question of claim construction: How narrowly will the court define the temporal limitation "prior to the first administration"? A narrow construction requiring a multi-week pretreatment window, as described in the patent's clinical trial example, could allow Defendants to design around the claim, whereas a broader construction could capture a wider range of label instructions.