Amgen Inc v. Mylan Pharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Amgen Inc. (Delaware)
  • Defendant: Mylan Pharmaceuticals Inc. (West Virginia) and Mylan Inc. (Pennsylvania)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Fitzpatrick, Cella, Harper & Scinto
• Case Identification: 1:17-cv-00113, D. Del., 02/03/2017
• Venue Allegations: Venue is alleged based on Defendants being registered to do business in Delaware, having a designated agent in the state, and having previously availed themselves of the district's courts without objecting to jurisdiction. The complaint also alleges Delaware would be a destination for the accused products upon approval.
• Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) for a generic version of the drug SENSIPAR® constitutes an act of infringement of a patent covering a rapid dissolution pharmaceutical formulation.
• Technical Context: The technology concerns pharmaceutical tablet formulations designed to improve the dissolution and bioavailability of cinacalcet hydrochloride, a compound used to treat secondary hyperparathyroidism in patients with chronic kidney disease.
• Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendants' notification to Plaintiff of their ANDA filing, which included a Paragraph IV Certification asserting that the patent-in-suit is invalid or will not be infringed. The complaint was filed within the 45-day statutory window, triggering an automatic 30-month stay of FDA approval for the generic product.

Case Timeline

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 9,375,405 - "Rapid Dissolution Formulation of a Calcium Receptor-Active Compound"

• Patent Identification: U.S. Patent No. 9,375,405, "Rapid Dissolution Formulation of a Calcium Receptor-Active Compound," issued June 28, 2016. (Compl. ¶13).

The Invention Explained

• Problem Addressed: The patent describes that the active compound, cinacalcet, is "insoluble or sparingly soluble in water," particularly at neutral pH, which can limit formulation options and result in low bioavailability for patients (’405 Patent, col. 6:10-21).
• The Patented Solution: The invention claims to solve this problem through a specific pharmaceutical composition—an oral tablet—that combines the active ingredient with a defined set of excipients (inactive ingredients) in particular weight-percentage ranges. This formulation is designed to achieve a "rapid dissolution" profile, ensuring the drug is released effectively in the acidic environment of the stomach, thereby improving its absorption and potential therapeutic effect (’405 Patent, col. 6:22-34; Abstract). The patent details a manufacturing process, including granulation and milling steps, to produce tablets with the desired characteristics (’405 Patent, Fig. 1).
• Technical Importance: Developing an effective oral dosage form for poorly soluble compounds is a common but significant challenge in pharmaceutical science, and this invention provides a specific formulation intended to overcome this hurdle for an important therapeutic agent (’405 Patent, col. 6:18-24).

Key Claims at a Glance

• The complaint asserts infringement of at least independent claim 1 (Compl. ¶37, 42).
• The essential elements of independent claim 1 are:
  • A pharmaceutical composition comprising:
  • (a) from about 10% to about 40% by weight of cinacalcet HCl in an amount of from about 20 mg to about 100 mg;
  • (b) from about 45% to about 85% by weight of a diluent selected from the group consisting of microcrystalline cellulose, starch, dicalcium phosphate, lactose, sorbitol, mannitol, sucrose, methyl dextrins, and mixtures thereof;
  • (c) from about 1% to about 5% by weight of at least one binder selected from the group consisting of povidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, and mixtures thereof; and
  • (d) from about 1% to 10% by weight of at least one disintegrant selected from the group consisting of crospovidone, sodium starch glycolate, croscarmellose sodium, and mixtures thereof.
• The complaint does not explicitly reserve the right to assert dependent claims, but the general allegation of infringing "at least claim 1" leaves this possibility open.

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are "Defendants' ANDA products," specifically identified as Mylan's "generic cinacalcet hydrochloride tablets (EQ 90 mg base)" described in ANDA No. 203422 (Compl. ¶6, 32).

Functionality and Market Context

• The accused product is a proposed generic version of Amgen's SENSIPAR® tablets, intended to be a therapeutic equivalent for treating secondary hyperparathyroidism and other conditions (Compl. ¶6, 19). The complaint alleges that the active ingredient in the accused ANDA product is cinacalcet hydrochloride (Compl. ¶34). The complaint does not provide specific details on the excipients or their proportions in the accused product, as this information is contained within the confidential ANDA filing. It does note, however, that Mylan provided a "Detailed Statement" of the factual and legal basis for its non-infringement and/or invalidity positions (Compl. ¶27).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The infringement allegation is a technical act of infringement under 35 U.S.C. § 271(e)(2)(A), based on the submission of an ANDA for a drug claimed in a patent (Compl. ¶36). The complaint alleges that the product described in the ANDA, if commercially manufactured and sold, would infringe the ’405 patent (Compl. ¶37).

’405 Patent Infringement Allegations

Identified Points of Contention

• Technical Questions: The central issue will be a direct factual comparison between the specific formulation detailed in Mylan's confidential ANDA and the compositional requirements of Claim 1. What specific diluents, binders, and disintegrants does Mylan's formulation use, and what are their precise weight percentages? The complaint does not provide this information, which will be a primary focus of discovery.
• Scope Questions: Do the quantitative ranges in Claim 1, modified by the term "about," encompass the percentages of the corresponding components in Mylan's formulation? The interpretation of "about" will be a key legal question influencing the scope of literal infringement.

V. Key Claim Terms for Construction

• The Term: "about"

• Context and Importance: This term appears in every quantitative limitation of claim 1 (e.g., "about 10% to about 40%"). Its construction is critical because infringement will depend on whether the exact percentages of ingredients in Mylan's product, if not identical to the claimed ranges, fall within the scope of what "about" permits. Practitioners may focus on this term because even a small deviation in Mylan's formulation could evade literal infringement if "about" is construed narrowly.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: A party might argue that "about" should be interpreted by the doctrine of equivalents or to account for normal manufacturing variances, consistent with its general meaning in the pharmaceutical arts.
  • Evidence for a Narrower Interpretation: The patent provides a detailed example with component weights specified to three or four decimal places (e.g., "Cinacalcet HCl... 18.367") (’405 Patent, col. 11, Table). A party could argue this high degree of precision implies that "about" should be given a very narrow range, encompassing only minor rounding or measurement tolerances.

• The Term: "diluent selected from the group consisting of..."

• Context and Importance: This limitation defines the permissible inactive ingredients that make up the bulk of the tablet. Infringement requires Mylan's product to use one or more of the specifically listed compounds as its diluent.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: A party arguing for a broader scope (likely through the doctrine of equivalents, not literal construction) might point to specification language describing the general function of diluents, suggesting that other chemically similar compounds performing the same function should be covered.
  • Evidence for a Narrower Interpretation: The phrase "selected from the group consisting of" is a term of art in patent law that creates a strong presumption that the list is closed and exhaustive. This suggests that any diluent used by Mylan that is not explicitly on this list would not literally infringe this element (’405 Patent, col. 14:21-26).

VI. Other Allegations

• Indirect Infringement: The complaint alleges that upon FDA approval, Defendants will induce and contribute to infringement by selling the ANDA product (Compl. ¶42). This allegation is based on the future expectation that product labeling and instructions will direct physicians and patients to use the product in an infringing manner.
• Willful Infringement: The complaint alleges that Defendants were aware of the ’405 patent at the time they notified Amgen of their Paragraph IV certification (Compl. ¶28). This alleged pre-suit knowledge forms the basis for a potential claim of willful infringement for any post-approval infringing sales. The prayer for relief also seeks a declaration that this is an exceptional case under 35 U.S.C. § 285 (Compl., Prayer for Relief ¶D).

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

• A central evidentiary question will be one of compositional identity: does the confidential formulation in Mylan's ANDA contain the specific diluents, binders, and disintegrants, within the specific weight-percentage ranges, as mandated by the elements of Claim 1 of the ’405 patent?
• The case will also turn on a question of definitional scope: how broadly will the court construe the term "about"? The answer will define the literal boundaries of the claimed quantitative ranges and determine whether Mylan’s formulation, if not identical, is nonetheless infringing.
• Finally, while not detailed in the complaint, a key issue for the court will be Mylan’s asserted defense of invalidity (Compl. ¶35). The court will have to determine whether the specific combination of known excipients in the claimed ranges would have been obvious to a person of ordinary skill in the art of pharmaceutical formulation at the time of the invention.