DCT
1:17-cv-02865
Eli Lilly Co v. Apotex Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Eli Lilly and Company (Indiana)
- Defendant: Apotex, Inc. (Canada)
- Plaintiff’s Counsel: Barnes & Thornburg LLP
- Case Identification: 1:17-cv-02865, S.D. Ind., 08/21/2017
- Venue Allegations: Plaintiff alleges venue is proper in the Southern District of Indiana because Defendant Apotex maintains a distribution and operation center in the district, intends to sell and distribute the accused products in Indiana, sent the required statutory notice letter to Plaintiff's headquarters in Indiana, and has previously litigated Hatch-Waxman cases in the district.
- Core Dispute: Plaintiff alleges that Defendant’s filing of a New Drug Application (NDA) for a generic version of the chemotherapy drug pemetrexed constitutes an act of infringement of a patent covering a method for administering pemetrexed in combination with vitamin B12 and folic acid to reduce patient toxicity.
- Technical Context: The technology concerns a method to improve the safety profile of antifolate chemotherapy agents, a class of drugs whose high toxicity can otherwise limit their clinical utility in cancer treatment.
- Key Procedural History: The complaint alleges that the patent-in-suit was the subject of prior litigation involving other generic manufacturers (Teva/APP Litigation), which resulted in a finding that the patent was not invalid and was infringed. The complaint further alleges that Apotex was party to a separate, earlier lawsuit on the same patent that was stayed pending the Teva/APP Litigation and resulted in a judgment against Apotex. Plaintiff asserts that these prior judgments bar Apotex from challenging the patent's validity or contesting infringement under the doctrines of res judicata and collateral estoppel.
Case Timeline
| Date | Event |
|---|---|
| 2000-06-30 | U.S. Patent No. 7,772,209 Priority Date |
| 2010-08-10 | U.S. Patent No. 7,772,209 Issue Date |
| 2012-03-07 | Apotex sends notice letter for prior ANDA No. 203774 |
| 2012-04-17 | Lilly files first suit against Apotex regarding the '209 patent |
| 2015-08-25 | Final judgment in related Teva/APP Litigation |
| 2017-01-12 | Federal Circuit affirms Teva/APP Litigation judgment |
| 2017-04-12 | Time for petition for writ of certiorari expires in Teva/APP case |
| 2017-07-31 | Apotex sends notice letter for current NDA No. 210661 |
| 2017-08-11 | Final judgment entered against Apotex in first lawsuit |
| 2017-08-21 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,772,209 - "Antifolate Combination Therapies"
The Invention Explained
- Problem Addressed: The patent describes how antifolate chemotherapy agents, while effective, are associated with "substantial toxicity," including severe and sometimes fatal side effects that have limited their clinical development and use (’209 Patent, col. 3:57-67).
- The Patented Solution: The invention is a method for improving the therapeutic utility of antifolates by administering them in combination with a "methylmalonic acid lowering agent," such as vitamin B12, and a folate binding protein agent, such as folic acid (’209 Patent, col. 3:5-10). The patent asserts the "surprising and unexpected" discovery that this vitamin pre-treatment regimen significantly reduces toxic events like skin rashes and fatigue "without adversely affecting therapeutic efficacy" (’209 Patent, col. 3:31-40).
- Technical Importance: This method provides a way to manage the dose-limiting toxicities of a potent class of cancer drugs, potentially making treatment safer and more tolerable for patients (’209 Patent, col. 3:26-30).
Key Claims at a Glance
- The complaint asserts infringement of claims 1-22 of the ’209 patent (Compl. ¶19). Independent claim 1 is central to the dispute.
- Essential elements of Independent Claim 1:
- A method for administering pemetrexed disodium to a patient in need thereof comprising administering an effective amount of folic acid
- and an effective amount of a methylmalonic acid lowering agent (such as vitamin B12)
- followed by administering an effective amount of pemetrexed disodium.
- The complaint reserves the right to assert dependent claims 2-22 (Compl. ¶19).
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are Apotex's Pemetrexed for Injection, 100 mg/vial and 500 mg/vial products ("Apotex's NDA Products") (Compl. ¶1). The act of infringement is Apotex's filing of New Drug Application (NDA) No. 210661 with the FDA seeking approval to market these products (Compl. ¶1, ¶22).
Functionality and Market Context
The complaint alleges that Apotex's NDA Products contain "pemetrexed disodium or its equivalent" and are intended to be marketed as a competing product to Plaintiff's ALIMTA®, a chemotherapy agent (Compl. ¶1, ¶17). The infringement theory is based on the use of the products as directed by their proposed labeling, which allegedly "involves administration of folic acid and vitamins B12" in a manner that would infringe the method claims of the ’209 patent (Compl. ¶18-19).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
’209 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for administering pemetrexed disodium to a patient in need thereof... | The use of Apotex's NDA Products, which contain "pemetrexed disodium or its equivalent," for the treatment of cancer. | ¶17, ¶19 | col. 4:40-43 |
| ...comprising administering an effective amount of folic acid... | The proposed labeling for Apotex's NDA Products directs the administration of folic acid to patients receiving the drug. | ¶18, ¶19 | col. 4:7-10 |
| ...and an effective amount of a methylmalonic acid lowering agent [such as vitamin B12]... | The proposed labeling for Apotex's NDA Products directs the administration of vitamin B12 to patients receiving the drug. | ¶18, ¶19 | col. 4:49-50 |
| ...followed by administering an effective amount of pemetrexed disodium... | The proposed labeling directs a sequence of administration where vitamin supplementation precedes the administration of pemetrexed. | ¶19 | col. 4:19-21 |
- Identified Points of Contention:
- Procedural Question: A threshold issue is whether the doctrines of res judicata or collateral estoppel, arising from the prior litigation cited in the complaint, preclude Apotex from contesting the validity of the ’209 patent or its infringement by a product used with the same vitamin regimen (Compl. ¶15). The court's handling of this issue may dispose of the case's technical questions.
- Scope Question: A key question for infringement, typical in Hatch-Waxman cases concerning method patents, is whether the instructions for use in Apotex's proposed product label will inevitably lead a physician to perform every step of the claimed method. The dispute may center on whether the label mandates the specific sequence and "effective amounts" required by the claims.
V. Key Claim Terms for Construction
The Term: "administering... followed by administering..."
- Context and Importance: This temporal limitation defines the sequence of the claimed method. Its construction is critical because infringement depends on whether Apotex's proposed label directs administration of the vitamins before the pemetrexed. Practitioners may focus on this term to determine if the label allows for a non-infringing simultaneous or post-administration of the vitamins.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent describes pre-treatment generally, stating "the mammal is pretreated with the methylmalonic acid lowering agent and then treated with the antifolate" (’209 Patent, col. 4:19-21). This general language could support a flexible reading of the timing between steps.
- Evidence for a Narrower Interpretation: The patent discloses specific clinical protocols, such as administering vitamin B12 "1 to 3 weeks before treatment with ALIMTA" and folic acid "beginning approximately 1 to 3 weeks before treatment" (’209 Patent, col. 9:15-20). A party could argue these specific embodiments narrow the scope of "followed by" to require a distinct pre-treatment period.
The Term: "effective amount"
- Context and Importance: This term appears for both the vitamins and the pemetrexed. The infringement analysis will depend on whether the dosages specified in Apotex's label meet the claimed "effective amount" for both reducing toxicity (for the vitamins) and treating the disease (for the pemetrexed).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent 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 suggests the term is not tied to a specific number but to achieving a particular outcome.
- Evidence for a Narrower Interpretation: The patent specification provides explicit dosage ranges, such as "about 350 µg to about 1000 µg of folic acid" and an intramuscular injection of "about 1000 µg" of vitamin B12 (’209 Patent, col. 8:9-10; col. 8:20). A party may argue that "effective amount" should be construed in light of, or limited to, these specific disclosed dosages.
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement of infringement under 35 U.S.C. § 271(b). The factual basis is the allegation that Apotex, with knowledge of the ’209 patent, will sell its NDA Products with a proposed label that instructs physicians and patients to perform the patented method (Compl. ¶24-25).
- Willful Infringement: The complaint does not use the word "willful," but it lays a foundation for such a claim. It alleges that Apotex has "knowledge of the claims of the '209 patent" and that this knowledge is based, in part, on extensive prior litigation over the very same patent (Compl. ¶13-15, ¶24). These allegations of pre-suit knowledge of the patent and specific infringing activity may support a later claim for enhanced damages. The prayer for relief also requests a finding that this is an "exceptional case" under 35 U.S.C. § 285 (Compl., Prayer for Relief (e)).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central threshold question will be one of issue preclusion: To what extent, if any, do the doctrines of res judicata and collateral estoppel, stemming from the prior Teva/APP Litigation and a previous judgment against Apotex on the same patent, bar Apotex from re-litigating the issues of patent validity and infringement for its new NDA product?
- Should the case proceed to the merits, a key evidentiary question will be one of induced infringement: Does the language of Apotex's proposed product label direct, encourage, or instruct healthcare providers to administer folic acid and vitamin B12 in "effective amounts" prior to the administration of pemetrexed, thereby meeting all limitations of the asserted method claim?