Amgen Inc v. Alkem Laboratories Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Amgen Inc. (Delaware)
  • Defendant: Alkem Laboratories Ltd. (India)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: 1:17-cv-00815, D. Del., 06/23/2017
• Venue Allegations: Venue is alleged as proper under 28 U.S.C. §§ 1391(b)-(c) and 1400(b), which govern venue in civil actions and patent infringement cases, respectively.
• Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) for generic cinacalcet hydrochloride tablets constitutes an act of infringement of a patent covering rapid dissolution formulations of the compound.
• Technical Context: The technology involves pharmaceutical formulations designed to achieve rapid dissolution of cinacalcet hydrochloride, a compound used to treat disorders related to parathyroid hormone levels, such as secondary hyperparathyroidism in patients with chronic kidney disease.
• Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 210570 and its Paragraph IV certification notice to Plaintiff, which asserted that the patent-in-suit is invalid or will not be infringed. The patent-in-suit is listed in the FDA's "Orange Book" as covering Plaintiff's SENSIPAR® product. The patent is subject to a terminal disclaimer.

Case Timeline

Date	Event
2003-09-12	U.S. Patent No. 9,375,405 Priority Date
2004-03-08	FDA Approval for SENSIPAR®
2011-02-25	Additional FDA Approval for SENSIPAR®
2016-06-28	U.S. Patent No. 9,375,405 Issue Date
2017-05-30	Defendant's Paragraph IV Certification Letter Date
2017-06-23	Complaint Filing Date

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

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 notes that certain calcium receptor-active compounds, such as cinacalcet HCl, are "insoluble or sparingly soluble in water," which can limit formulation options and lead to low bioavailability of the drug when administered to a patient ('405' Patent, col. 1:10-24).
• The Patented Solution: The invention provides a pharmaceutical composition with a specific combination of cinacalcet HCl and certain excipients (inactive ingredients) that results in a "defined dissolution profile" ('405 Patent, col. 1:29-32). As described in the specification and illustrated in the process flow diagram of FIG. 1, the components are processed through steps like granulation and milling to create a formulation that rapidly releases the active ingredient when tested ('405 Patent, FIG. 1; col. 9:18-49).
• Technical Importance: This formulation technology aims to improve the dissolution characteristics of a poorly soluble but therapeutically important drug, thereby enabling effective and reliable oral delivery for treating conditions like hyperparathyroidism (Compl. ¶17; '405 Patent, col. 1:19-24).

Key Claims at a Glance

• The complaint asserts at least independent claim 1 (Compl. ¶31).
• The essential elements of independent claim 1 are:
  • A specific amount and weight percentage of cinacalcet HCl: "from about 10% to about 40% by weight... in an amount of from about 20 mg to about 100 mg"
  • A specific weight percentage of a diluent chosen from a defined list: "from about 45% to about 85% by weight"
  • A specific weight percentage of a binder chosen from a defined list: "from about 1% to about 5% by weight"
  • A specific weight percentage of a disintegrant chosen from a defined list: "from about 1% to 10% by weight"
  • A statement of purpose: "wherein the composition is for the treatment of at least one of hyperparathyroidism, hyperphosphonia, hypercalcemia, and elevated calcium phosphorus product" ('405 Patent, col. 13:17 - col. 14:1).

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are Defendant’s proposed generic cinacalcet hydrochloride tablets in 30 mg, 60 mg, and 90 mg dosage strengths, for which Defendant filed ANDA No. 210570 with the FDA (Compl. ¶4, ¶26).

Functionality and Market Context

• The complaint alleges that the ANDA products are generic versions of Plaintiff's SENSIPAR® tablets, intended to be used for the same medical indications, namely the treatment of secondary hyperparathyroidism and hypercalcemia (Compl. ¶14-16, ¶20). The filing of the ANDA signifies Defendant's intent to commercially manufacture and sell these products in the United States upon receiving FDA approval (Compl. ¶20, ¶26).

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or a detailed narrative of its infringement theory beyond the statutory allegation that filing the ANDA constitutes infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶30). The central allegation, made "upon information and belief," is that the ANDA products, if commercially manufactured and sold, would infringe at least claim 1 of the ’405 patent, either literally or under the doctrine of equivalents (Compl. ¶31). The factual basis for this belief, likely derived from the contents of Defendant's confidential ANDA submission, is not detailed in the complaint. No probative visual evidence provided in complaint.

Identified Points of Contention

• Scope Questions: The primary dispute will likely center on whether the formulation detailed in Defendant's confidential ANDA falls within the specific weight percentage ranges for each category of ingredient recited in claim 1. A formulation that falls outside even one of the claimed ranges for the active ingredient, diluent, binder, or disintegrant may support a non-infringement defense.
• Technical Questions: A key evidentiary question will be the precise composition of Defendant's ANDA product. As this information is not public, the infringement analysis will depend entirely on comparing the formulation disclosed in the ANDA filing with the specific limitations of the asserted claims.

V. Key Claim Terms for Construction

The Term: "about"

• Context and Importance: This term is used to define the boundaries of every compositional range in claim 1. Its interpretation is critical because in ANDA litigation, even a small deviation from a numeric range can be the basis for a non-infringement argument. Practitioners may focus on this term to determine if Defendant's formulation, if slightly outside a recited number, is nonetheless infringing.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification uses the term "about" frequently when discussing dosages, percentages, and process parameters, which may suggest the patentees did not intend for the numerical ranges to be rigid and absolute cutoffs ('405 Patent, col. 4:10, col. 7:20, col. 9:8).
  • Evidence for a Narrower Interpretation: The patent discloses example formulations with highly specific weight percentages (e.g., "18.367") and reports dissolution data with precision, which could be used to argue that "about" should be construed narrowly and does not afford significant flexibility ('405 Patent, col. 11, Table; col. 12, Table 2).

The Term: "binder," "diluent," "disintegrant"

• Context and Importance: Claim 1 defines these functional excipient categories using Markush groups listing specific chemical compounds. The proper classification of an ingredient in Defendant's formulation will be critical. A dispute may arise if Defendant uses an excipient that has multiple pharmaceutical functions or is not explicitly listed, as its classification could shift the weight percentages of the formulation into or out of the claimed ranges.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent lists examples of these excipients in a manner that suggests reliance on their well-understood, conventional functions in the pharmaceutical arts ('405 Patent, col. 6:57-64). A party could argue the terms should be given their plain and ordinary meaning to a person of ordinary skill in the art.
  • Evidence for a Narrower Interpretation: The claims explicitly list the members of each group (e.g., "binder selected from the group consisting of povidone..."). A party could argue that an ingredient not listed, or one that functions differently from the listed examples in the context of the invention, falls outside the scope of the claim.

VI. Other Allegations

Indirect Infringement

• The complaint alleges that Defendant's future activities will induce and/or contribute to the infringement of the ’405 patent (Compl. ¶36). The alleged factual basis is Defendant's intent to sell the ANDA products immediately upon FDA approval for the same indications as SENSIPAR®, which would necessarily involve instructing physicians and patients to use the product in an infringing manner (Compl. ¶35-36).

Willful Infringement

• The complaint does not explicitly allege willfulness, but it requests a declaration that the case is "exceptional" under 35 U.S.C. § 285, which allows for the award of attorney fees (Compl., Prayer for Relief ¶D). The factual basis for this claim appears to be pre-suit knowledge, as the complaint alleges Defendant was aware of the ’405 patent at the time it sent its Paragraph IV certification letter (Compl. ¶22).

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

• A core issue will be one of compositional identity: Will discovery of Defendant's confidential ANDA filing reveal a formulation that includes the specific excipients and falls within every weight percentage range recited in claim 1 of the ’405 patent?
• A key legal question will be one of definitional scope: How will the court construe the term "about"? The breadth of this term will determine whether a formulation that deviates slightly from the explicit numerical ranges in the claims can be found to infringe.
• A central technical question will turn on the functional classification of excipients: Should an ingredient in the accused product that possesses multiple pharmaceutical properties be classified as a "binder," "diluent," or "disintegrant" for the purpose of comparing its weight percentage to the limitations of claim 1?