Amgen Inc v. Zydus Pharma USA Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Amgen Inc. (Delaware)
  • Defendant: Zydus Pharmaceuticals (USA) Inc. (New Jersey) and Cadila Healthcare Ltd. (India)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: 1:17-cv-00183, D. Del., 02/21/2017
• Venue Allegations: Venue is alleged to be proper based on Defendants transacting business in Delaware, planning to sell the accused products in Delaware, and having previously availed themselves of Delaware courts in other litigation.
• Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) for generic cinacalcet hydrochloride tablets constitutes an act of infringement of a patent covering a rapid dissolution formulation for that compound.
• Technical Context: The technology concerns pharmaceutical formulations designed to improve the dissolution and bioavailability of cinacalcet, a compound used to treat disorders related to hyperparathyroidism.
• Key Procedural History: The litigation was triggered by Zydus USA’s filing of ANDA No. 208971 and its associated Paragraph IV Certification, which asserted that the patent-in-suit is invalid or would not be infringed by the proposed generic product. Amgen filed this complaint within the 45-day window provided by the Hatch-Waxman Act, triggering a statutory 30-month stay of FDA approval for the ANDA.

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.

The Invention Explained

• Problem Addressed: The patent’s background section explains that certain calcium receptor-active compounds, such as cinacalcet HCl, are “insoluble or sparingly soluble in water,” particularly at neutral pH (’405 Patent, col. 1:10-13). This limited solubility can reduce the number of available formulation options and may result in “low bioavailability” of the active compound when administered to a patient (’405 Patent, col. 1:18-24).
• The Patented Solution: The invention is a pharmaceutical composition that combines the active ingredient, cinacalcet HCl, with a specific combination of pharmaceutically acceptable excipients (carriers) to achieve a "defined dissolution profile" (’405 Patent, col. 2:30-32, Abstract). By controlling the types and relative amounts of components like diluents, binders, and disintegrants, the formulation is designed to release the active drug compound rapidly when tested under specific laboratory conditions, thereby aiming to improve its absorption in the body (’405 Patent, col. 8:12-25).
• Technical Importance: For a drug with poor water solubility, a formulation that enhances its dissolution rate can be critical for achieving consistent and effective therapeutic levels in the bloodstream.

Key Claims at a Glance

• The complaint asserts infringement of at least independent claim 1 (Compl. ¶37).
• 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 a specific list including microcrystalline cellulose and starch;"
  • "(c) from about 1% to about 5% by weight of at least one binder selected from a specific list including povidone;"
  • "(d) from about 1% to 10% by weight of at least one disintegrant selected from a specific list including crospovidone;"
  • "wherein the percentage by weight is relative to the total weight of the composition, and wherein the composition is for the treatment of" specific diseases such as hyperparathyroidism.
• The complaint does not explicitly reserve the right to assert dependent claims, but alleges infringement of the patent generally.

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are Defendants' generic "cinacalcet hydrochloride tablets (EQ 30 mg base, EQ 60 mg base, and EQ 90 mg base)" for which Defendants filed Abbreviated New Drug Application (ANDA) No. 208971 with the FDA (Compl. ¶7).

Functionality and Market Context

• The complaint alleges that the Defendants’ ANDA products are generic versions of Amgen’s SENSIPAR® tablets (Compl. ¶24, ¶26). Under the Hatch-Waxman Act, an ANDA product must have the same active ingredient, strength, dosage form, and route of administration as the reference listed drug. The complaint alleges that Defendants seek approval to market these products for the same indications as SENSIPAR®, which is used to treat secondary hyperparathyroidism in patients with chronic kidney disease and hypercalcemia in patients with parathyroid carcinoma (Compl. ¶19).

IV. Analysis of Infringement Allegations

The complaint does not include a claim chart or detailed technical allegations. The infringement theory is statutory under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a generic drug before patent expiration as an act of infringement. The following table summarizes the infringement theory implied by the ANDA filing for a composition claim.

No probative visual evidence provided in complaint.

’405 Patent Infringement Allegations

• Identified Points of Contention:
  • Scope Questions: A central question will be whether the specific formulation detailed in the confidential ANDA filing literally falls within the claimed ranges. The dispute may turn on whether Zydus's formulation uses different excipients, or the same excipients in proportions that fall outside the claimed weight percentages.
  • Technical Questions: Since the ANDA is not public, the primary technical question is what Zydus’s formulation actually contains. This will be the subject of discovery. The Defendants' Paragraph IV letter states the patent is "invalid or will not be infringed," raising the factual question of how the Zydus formulation differs from the claimed invention (Compl. ¶27).

V. Key Claim Terms for Construction

• The Term: "about"
• Context and Importance: This term appears in the limitations defining the weight percentages of all key ingredients in claim 1 (e.g., "about 10% to about 40%"). The scope of "about" will be critical to determining literal infringement. If the Defendants’ formulation uses a weight percentage just outside a recited numerical range (e.g., 9.9% cinacalcet HCl), the case could turn entirely on whether that value is "about 10%." Practitioners may focus on this term because small variations in formulation components are common grounds for non-infringement arguments in ANDA litigation.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent uses the term "about" consistently throughout the claims and specification when discussing ranges, which may suggest the patentee intended the term to have its ordinary meaning of "approximately" to account for normal manufacturing and measurement tolerances (’405 Patent, col. 7:20-25, col. 12:18-34).
  • Evidence for a Narrower Interpretation: The patent provides a detailed example formulation with exact percentages to three decimal places (e.g., "18.367" % cinacalcet HCl) (’405 Patent, col. 11, Table). A party could argue this precise disclosure implies that "about" was not intended to cover significant deviations from the recited values. Further, the patent links the formulation to a specific dissolution profile, which could be used to argue that "about" should be limited to only those variations that still achieve the disclosed dissolution results (’405 Patent, col. 8:12-25).

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Defendants will induce and/or contribute to infringement upon FDA approval (Compl. ¶42). The alleged factual basis for this is that Defendants will market and sell their generic product with a label and instructions that encourage medical professionals and patients to use the product in an infringing manner for the patented therapeutic indications.
• Willful Infringement: The complaint does not use the word "willful," but it requests a declaration that this is an "exceptional case" under 35 U.S.C. § 285, which permits an award of attorney fees (Prayer ¶D). The factual basis for this is the allegation that Defendants were aware of the ’405 patent at the time they notified Amgen of their Paragraph IV certification, thereby proceeding with their efforts to market a generic product despite knowledge of Amgen's patent rights (Compl. ¶28).

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

• A core issue will be one of claim scope: can the term "about," as used to define the weight percentages of the formulation's components, be construed broadly enough to read on the specific percentages used in the Defendants' ANDA product, or will the court adopt a narrower definition that allows the accused product to escape infringement?
• A central factual question will be one of compositional identity: does the confidential formulation disclosed in Zydus’s ANDA actually contain the specific diluents, binders, and disintegrants required by claim 1, and in the claimed proportions? The outcome of the infringement analysis depends entirely on the answer, which will be revealed during discovery.
• The case will also likely involve a significant dispute over validity: Defendants have certified the patent is invalid. This raises the question of whether the claimed formulation—a specific combination of generally known pharmaceutical excipients—was non-obvious to a person of ordinary skill in the art at the time of the invention, or whether it would have been obvious to try this combination to solve the known dissolution problems of cinacalcet HCl.