DCT
1:16-cv-00431
Novartis Pharma Corp v. Breckenridge Pharmaceutical Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Novartis Pharmaceuticals Corporation (Delaware) and Novartis AG (Switzerland)
- Defendant: Breckenridge Pharmaceutical, Inc. (Florida)
- Plaintiff’s Counsel: McCarter & English, LLP; Fitzpatrick, Cella, Harper & Scinto
- Case Identification: 1:16-cv-00431, D. Del., 06/10/2016
- Venue Allegations: Venue is alleged based on Defendant’s business activities throughout the United States, including in Delaware, and specifically on its filing of an Abbreviated New Drug Application (ANDA) seeking approval to market its generic product in the district.
- Core Dispute: Plaintiffs allege that Defendant’s submission of an ANDA to the FDA to market a generic version of Plaintiffs’ AFINITOR® (everolimus) tablets constitutes an act of infringement of three U.S. patents covering the everolimus compound and its methods of use for treating specific cancers.
- Technical Context: The technology concerns everolimus, a derivative of the macrolide rapamycin, which functions as an mTOR inhibitor for use in oncology, specifically for the treatment of various solid tumors.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s ANDA filing containing a Paragraph IV certification, which asserts that Plaintiffs' patents are invalid and/or not infringed. Plaintiffs filed the complaint within the 45-day statutory window after receiving Defendant's notice letter, triggering a 30-month stay on FDA approval of the generic product. Notably, the lead patent, U.S. Patent No. 5,665,772, previously survived an Inter Partes Review (IPR) proceeding (IPR2016-00084), which confirmed the patentability of claims 1-3 and 8-10.
Case Timeline
| Date | Event |
|---|---|
| 1992-10-09 | ’772 Patent Priority Date |
| 1997-09-09 | ’772 Patent Issue Date |
| 2001-02-19 | ’131 and ’962 Patents Priority Date |
| 2009-03-30 | FDA Approval of AFINITOR® (everolimus) tablets |
| 2013-04-02 | ’131 Patent Issue Date |
| 2014-07-15 | ’962 Patent Issue Date |
| 2016-04-28 | Plaintiffs receive Defendant's ANDA Notice Letter |
| 2016-06-10 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 5,665,772 - O-ALKYLATED RAPAMYCIN DERIVATIVES AND THEIR USE, PARTICULARLY AS IMMUNOSUPPRESSANTS
The Invention Explained
- Problem Addressed: The patent identifies that while the natural compound rapamycin is a potent immunosuppressant, its utility as a pharmaceutical is limited by its very low and variable bioavailability, high toxicity, and poor solubility, which complicates the creation of stable formulations (’772 Patent, col. 1:32-40).
- The Patented Solution: The invention provides novel derivatives of rapamycin created by modifying the molecule at the C40 position. This O-alkylation, specifically creating 40-O-(2-hydroxyethyl)-rapamycin (everolimus), results in compounds with an improved pharmacological profile, including greater stability and bioavailability, making them more suitable as therapeutic agents (’772 Patent, Abstract; col. 2:56-62).
- Technical Importance: This chemical modification was a key step in transforming a promising but problematic natural compound into a viable clinical drug by improving its drug-like properties (’772 Patent, col. 1:41-47).
Key Claims at a Glance
- The complaint alleges infringement of "one or more claims" (Compl. ¶25). Claim 10 is the narrowest independent claim covering the specific compound at issue.
- Independent Claim 10 (as corrected June 30, 1998):
- A compound which is 40-O-(2-hydroxyethyl)-rapamycin.
U.S. Patent No. 8,410,131 - CANCER TREATMENT
The Invention Explained
- Problem Addressed: The patent addresses the general need for new and effective treatments for solid tumors, particularly for advanced solid tumors where existing therapies may not provide disease regression or stabilization (’131 Patent, col. 1:53-62).
- The Patented Solution: The invention is a second medical use patent, claiming a method of treating specific cancers by administering the previously known compound everolimus. The patent discloses that everolimus has potent antiproliferative properties suitable for cancer chemotherapy (’131 Patent, col. 1:56-59; col. 3:56-62). The claims are directed to methods of inhibiting the growth of specific tumor types, such as those of the excretory system.
- Technical Importance: The invention repurposes an existing drug, known primarily for its immunosuppressive properties, as a targeted therapy for specific types of cancer, expanding its therapeutic value.
Key Claims at a Glance
- The complaint alleges infringement of the method for inhibiting growth of solid excretory system tumors (Compl. ¶16).
- Independent Claim 1:
- A method for inhibiting growth of solid excretory system tumors in a subject,
- said method consisting of administering to said subject a therapeutically effective amount of a compound of formula I [which includes everolimus].
U.S. Patent No. 8,778,962 - TREATMENT OF SOLID TUMORS WITH RAPAMYCIN DERIVATIVES
Technology Synopsis
This patent addresses the need for therapies for non-malignant solid tumors of the brain (’962 Patent, Abstract). It discloses that administering everolimus is an effective method for inhibiting the growth of such tumors, further expanding the compound's known medical uses (’962 Patent, Claim 1).
Asserted Claims
The complaint asserts infringement of the method claim for inhibiting growth of non-malignant solid tumors of the brain (Compl. ¶18). Claim 1 is the primary independent claim.
Accused Features
Plaintiffs allege that Defendant's generic product will be approved and labeled with instructions for this indication, which would induce infringement by doctors and patients (Compl. ¶¶ 29-30).
III. The Accused Instrumentality
Product Identification
Defendant’s Abbreviated New Drug Application (“ANDA”) Product, which is a generic version of everolimus tablets in a 10 mg dosage strength (Compl. ¶19).
Functionality and Market Context
- The accused product is a generic pharmaceutical intended to be a bioequivalent substitute for Plaintiffs’ brand-name drug, AFINITOR® (Compl. ¶11, ¶19). On information and belief, it will contain the same active pharmaceutical ingredient, everolimus, and will be prescribed for the same FDA-approved indications as AFINITOR® (Compl. ¶¶ 26-30). These indications include the treatment of certain types of kidney cancer, breast cancer, and other tumors (Compl. ¶11).
- The complaint alleges that Defendant’s filing of the ANDA is a statutory act of infringement under the Hatch-Waxman Act, signaling its intent to commercially manufacture and sell the product before the expiration of the patents-in-suit (Compl. ¶¶ 19, 23).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’772 Patent Infringement Allegations
| Claim Element (from Independent Claim 10) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| The compound... which is 40-O-(2-hydroxyethyl)-rapamycin. | The complaint alleges that Defendant's ANDA Product, if approved, "will contain everolimus," which is chemically known as 40-O-(2-hydroxyethyl)-rapamycin. The submission of the ANDA to market this compound is the alleged act of infringement. | ¶12, ¶19, ¶26 | col. 12:53-65 |
’131 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for inhibiting growth of solid excretory system tumors in a subject, | Plaintiffs allege the Defendant’s product will be labeled for use in treating, among other things, "advanced renal cell carcinoma," which is a solid excretory system tumor. The proposed label is alleged to instruct physicians and patients to perform the claimed method. | ¶11, ¶16, ¶27-28 | col. 2:27-29 |
| said method consisting of administering to said subject a therapeutically effective amount of... [everolimus]. | The complaint alleges the ANDA product contains everolimus and that its label "will contain instructions for administering a therapeutically effective amount of everolimus" for the patented use, thereby inducing infringement. | ¶27-28 | col. 3:64-col. 4:2 |
Identified Points of Contention
- Scope Questions: For the '131 and '962 patents, a primary dispute may arise over whether the specific language of the proposed product label will be found to encourage, recommend, or promote an infringing use, which is the standard for inducement. The analysis will depend on the exact wording of the indications and instructions on the label that the FDA ultimately approves.
- Technical Questions: For the '772 patent, infringement appears to be a direct consequence of the ANDA filing itself, assuming the generic product contains everolimus as stated. The central dispute for this patent, as signaled by the Paragraph IV certification (Compl. ¶20), will likely revolve around validity (e.g., obviousness or anticipation), though Plaintiffs' position may be strengthened by the prior favorable IPR outcome.
V. Key Claim Terms for Construction
The Term
"consisting of" (’131 Patent, Claim 1)
Context and Importance
This term is a critical term of art in patent law that creates a "closed" claim, meaning the claimed method includes only the specified step(s) and no others. Practitioners may focus on this term because infringement of the method-of-use claim depends on whether the administration of everolimus as directed by the generic label constitutes the entire method. If the label requires or suggests co-administration of other active agents, Defendant may argue that the method practiced is not the one "consisting of" only the administration of everolimus, thereby avoiding infringement.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: A plaintiff would argue that "consisting of" applies to the active steps of inhibiting tumor growth, and does not exclude preparatory steps or the presence of inactive excipients in the formulation. The core of the method is the administration of the single active agent, everolimus.
- Evidence for a Narrower Interpretation: The patent specification describes numerous potential combination therapies where everolimus is used with other chemotherapeutic agents (’131 Patent, col. 4:37-col. 8:65). A defendant may argue that by choosing the highly restrictive "consisting of" language for the claim, the patentee explicitly disclaimed coverage for such combination therapies, limiting the claim to monotherapy only.
VI. Other Allegations
Indirect Infringement
The complaint alleges both induced and contributory infringement for all three patents (Compl. ¶25). For the method patents (’131 and ’962), inducement is based on the allegation that Defendant’s product, once approved, will be "specifically labeled for use" in the patented methods and that its instructions will "actively induce, encourage, and abet this infringement" (Compl. ¶27, ¶29). Contributory infringement is alleged on the basis that the product is a material part of the patented methods, is especially adapted for an infringing use, and is not suitable for a substantial non-infringing use (Compl. ¶28, ¶30).
Willful Infringement
The complaint does not contain an explicit allegation of willful infringement or a request for enhanced damages. However, it does allege that Defendant was "aware of the '772, '131 and '962 patents" when it filed its ANDA, establishing the knowledge element required for indirect infringement and potentially forming a basis for a future willfulness argument (Compl. ¶24).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of patent validity versus estoppel: Given that key claims of the '772 patent were confirmed as patentable in an Inter Partes Review, to what extent can the defendant re-litigate the validity of those claims in district court using the same or similar prior art?
- A key legal question will be one of claim scope and disclaimer: Does the use of the restrictive term "consisting of" in the '131 patent's method claim, when read in light of the specification's extensive discussion of combination therapies, limit the claim's scope to monotherapy only, potentially allowing a generic to avoid infringement if its label permits co-administration of other drugs?
- A determinative evidentiary question will be one of infringement by labeling: Will the final, FDA-approved label for the Defendant's generic product contain explicit instructions that direct users to perform the exact methods claimed in the '131 and '962 patents, or will the instructions be for a broader use that does not map directly onto the claim limitations?