Novartis Pharma Corp v. Mylan Pharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Novartis Pharmaceuticals Corporation (Delaware) and Novartis AG (Switzerland)
  • Defendant: Mylan Pharmaceuticals Inc. (West Virginia)
  • Plaintiff’s Counsel: McCarter & English, LLP
• Case Identification: 1:19-cv-01042, D. Del., 06/05/2019
• Venue Allegations: Venue is asserted based on Defendant being registered to do business in Delaware, maintaining a designated agent for service of process in the state, holding state-issued pharmaceutical licenses, and filing an Abbreviated New Drug Application (ANDA) that constitutes a formal act indicating intent to market the accused products in Delaware.
• Core Dispute: Plaintiffs allege that Defendant's submission of an ANDA to the FDA seeking approval to market generic everolimus tablets infringes three U.S. patents covering the everolimus compound and its methods of use for treating specific medical conditions.
• Technical Context: The dispute centers on everolimus, a derivative of the macrolide rapamycin, which possesses antiproliferative and immunosuppressant properties and is the active ingredient in Plaintiffs' cancer therapy drug, AFINITOR®.
• Key Procedural History: This action was filed under the Hatch-Waxman Act within 45 days of Plaintiffs’ receipt of a Paragraph IV certification notice letter from Defendant, dated April 23, 2019. This filing triggers a statutory 30-month stay of FDA approval for the accused generic product. The notice letter asserted that claims of the patents-in-suit were invalid and/or would not be infringed. One patent-in-suit, U.S. Patent No. 5,665,772, was the subject of an Inter Partes Review (IPR), which concluded in May 2019 with a finding that asserted claims 1-3 and 8-10 are patentable.

Case Timeline

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," Issued September 9, 1997

The Invention Explained

• Problem Addressed: The patent describes rapamycin as a potent immunosuppressant and antitumor agent whose pharmaceutical utility is limited by its "very low and variable bioavailability," "high toxicity," and high insolubility, which complicates the formulation of stable compositions (’772 Patent, col. 1:33-40).
• The Patented Solution: The invention claims to solve these problems through novel O-alkylated derivatives of rapamycin (’772 Patent, col. 1:4-9). These new compounds, particularly the 40-O-substituted derivatives, are described as having an "improved pharmacologic profile," "greater stability and bioavailability," and allowing for "greater ease in producing galenic formulations" (’772 Patent, col. 1:41-48). The specification provides a specific synthesis for 40-O-(2-hydroxyethyl)-rapamycin, the compound known as everolimus (’772 Patent, Example 8, col. 12:30-68).
• Technical Importance: The claimed chemical modifications sought to convert a powerful but difficult-to-administer natural compound into a viable therapeutic drug with a more predictable and favorable clinical profile (’772 Patent, col. 1:41-44).

Key Claims at a Glance

• The complaint asserts claims 1-3 and 7-10 (Compl. ¶21). Independent claims 1 and 7 are central.
• Independent Claim 1:
  • A compound of the formula I (a rapamycin macrocycle with an R¹O- group at the C40 position)
  • Wherein the R¹ group is a hydroxy(C1-6)alkyl or a hydroxy(C1-3)alkoxy(C1-3)alkyl
• Independent Claim 7:
  • A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1
  • And a pharmaceutically acceptable carrier
• The complaint notes that Defendant did not deny infringement of claims 1-3, 7, and 10 in its notice letter (Compl. ¶27).

U.S. Patent No. 8,436,010 - "TREATMENT OF SOLID TUMORS WITH RAPAMYCIN DERIVATIVES," Issued May 7, 2013

The Invention Explained

• Problem Addressed: The patent background describes the known immunosuppressive uses of rapamycin derivatives and identifies a need for new cancer therapies, stating, "It has now been found that Compounds of formula I have potent antiproliferative properties which make them useful for cancer chemotherapy, particularly of solid tumors" (’010 Patent, col. 2:59-62).
• The Patented Solution: The patent claims methods of using specific rapamycin derivatives to treat solid tumors. The invention covers the administration of 40-O-(2-hydroxyethyl)-rapamycin (everolimus) concomitantly or sequentially with another anticancer agent, exemestane, for the specific purpose of inhibiting the growth of solid breast tumors (’010 Patent, Claim 1).
• Technical Importance: The invention represents a repurposing and combination-therapy application of a known class of compounds, expanding their therapeutic utility from immunosuppression to a specific oncology indication (’010 Patent, Abstract).

Key Claims at a Glance

• The complaint asserts claims 1-11 (Compl. ¶21). Independent claim 1 is central.
• Independent Claim 1:
  • A method for inhibiting growth of solid tumors of the breast in a subject with a solid breast tumor
  • The method consists of administering a therapeutically effective amount of a specific compound of formula I, which is 40-O-(2-hydroxyethyl)-rapamycin (everolimus)
  • The administration is performed concomitantly or sequentially with exemestane
• The complaint reserves the right to assert other claims in the patent (Compl. ¶25).

Multi-Patent Capsule

• Patent Identification: U.S. Patent No. 8,778,962, "TREATMENT OF SOLID TUMORS WITH RAPAMYCIN DERIVATIVES," Issued July 15, 2014.
• Technology Synopsis: The patent discloses methods of using rapamycin derivatives for treating solid tumors, based on the discovery of their "potent antiproliferative properties" (’962 Patent, col. 2:59-62). The asserted claims are directed specifically to a method of inhibiting the growth of non-malignant solid tumors of the brain by administering a therapeutically effective amount of everolimus (’962 Patent, Claim 1).
• Asserted Claims: 1-6 (Compl. ¶21).
• Accused Features: The complaint alleges that Defendant’s ANDA product, if approved, will include labeling with instructions for administering everolimus for this patented use, which will cause infringement (Compl. ¶28).

III. The Accused Instrumentality

Product Identification

• Defendant’s Abbreviated New Drug Application (ANDA) seeking FDA approval to manufacture and sell generic everolimus tablets in 2.5 mg, 5 mg, 7.5 mg, and 10 mg dosage strengths (Compl. ¶20).

Functionality and Market Context

• The accused instrumentality is a proposed generic drug product intended to be a bioequivalent substitute for Plaintiffs’ AFINITOR® tablets (Compl. ¶¶ 12, 20). In the context of this Hatch-Waxman litigation, the infringing act is the filing of the ANDA itself, which seeks approval for a product that allegedly embodies the composition claimed in the ’772 patent (Compl. ¶26). Further, the complaint alleges that the proposed labeling for the ANDA product will contain instructions for use that will track the approved indications for AFINITOR®, thereby instructing physicians and patients to perform the methods claimed in the ’962 and ’010 patents (Compl. ¶¶ 28, 30).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

U.S. Patent 5,665,772 Infringement Allegations

(Based on Asserted Independent Claim 7)

U.S. Patent 8,436,010 Infringement Allegations

(Based on Asserted Independent Claim 1)

Identified Points of Contention

• Validity vs. Infringement: For the ’772 patent, the complaint notes that Defendant's notice letter did not contest infringement of key claims, instead focusing on invalidity (Compl. ¶¶ 21, 27). Given that these claims recently survived an IPR, a central point of contention will be whether Defendant can meet the high burden of proving invalidity by clear and convincing evidence, particularly on grounds that may have been previously considered by the USPTO.
• Evidentiary Questions (Method Claims): For the ’010 and ’962 patents, infringement hinges on the final, FDA-approved label for Defendant's generic product. The complaint alleges on "information and belief" that the label will instruct infringement (Compl. ¶¶ 28, 30). A key question for the court will be whether the evidence, once developed, confirms that the proposed label directs users to perform the patented methods.

V. Key Claim Terms for Construction

• The Term: "consisting of" (as used in ’010 Patent, Claim 1 and ’962 Patent, Claim 1)

  • Context and Importance: This is a restrictive term of art in patent law that limits the claim to only the specified elements. Practitioners may focus on this term because if Defendant's proposed label requires an additional, unlisted active step or agent for the method to be practiced, it could support a straightforward non-infringement argument.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party seeking a broader scope might argue that the term does not exclude unclaimed steps that are unrelated or immaterial to the core invention, though this is generally a difficult argument to win. The patent does not appear to provide explicit support for such a reading.
    • Evidence for a Narrower Interpretation: The plain meaning of "consisting of" is exclusionary. The claim language itself—for example, "said method consisting of administering...everolimus concomitantly or sequentially with exemestane" (’010 Patent, col. 10:50-52)—provides the primary evidence for a narrow, closed interpretation.

• The Term: "therapeutically effective amount" (as used in ’772 Patent, Claim 7; ’010 Patent, Claim 1; ’962 Patent, Claim 1)

  • Context and Importance: The definition of this term is central to both infringement and validity. The dispute may involve whether the specific dosage strengths in Defendant's ANDA (2.5 mg, 5 mg, 7.5 mg, 10 mg) constitute a "therapeutically effective amount" for the methods claimed in the ’010 and ’962 patents.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The ’772 patent specification discloses broad dosage ranges, such as "on the order of from 0.05 to 5 or up to 10 mg/kg/day" orally, which could support a wide range of doses being considered effective (’772 Patent, col. 4:37-40).
    • Evidence for a Narrower Interpretation: The patents also contain clinical trial data and specific examples that might be used to argue for a more constrained definition tied to achieving a specific clinical outcome or limited to dosages proven effective in the patent's own examples (’010 Patent, col. 9:45-67).

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Defendant will induce and contribute to infringement of the ’962 and ’010 method patents (Compl. ¶¶ 28-31). The factual basis for these allegations is that Defendant's product will be "specifically labeled for" the patented uses and that its accompanying instructions will "actively encourage, recommend, or promote" infringement by physicians and patients. The complaint also alleges the product is "not suitable for a substantial noninfringing use" for the claimed methods, a requirement for contributory infringement (Compl. ¶¶ 29, 31).
• Willful Infringement: The complaint does not contain an explicit allegation of willful infringement or a request for enhanced damages. It does, however, allege that Defendant was aware of the patents-in-suit when it filed its ANDA, which is a necessary predicate for any future willfulness claim (Compl. ¶24).

VII. Analyst’s Conclusion: Key Questions for the Case

• A central question of validity: Given that Defendant’s defense, as foreshadowed in its notice letter, centers on invalidity and the ’772 patent recently survived an Inter Partes Review, a core issue for the court will be whether Defendant can establish by clear and convincing evidence that the asserted claims are invalid on grounds not already overcome during prosecution and re-examination.
• An evidentiary question of induced infringement: Will the final, FDA-approved label for Defendant's generic product contain language that instructs or encourages physicians to prescribe the drug in a manner that directly practices the specific methods of use claimed in the ’010 and ’962 patents? The outcome of the inducement claims will likely depend on the precise text of that label.