DCT

1:15-cv-00839

Amgen Inc v. Hospira Inc

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Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:15-cv-00839, D. Del., 11/06/2015
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware based on Defendant being a Delaware corporation that has conducted business and engaged in substantial and continuing contacts within the District.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of a Biologic License Application (BLA) for a biosimilar version of Plaintiff's EPOGEN® product constitutes infringement of patents related to specific erythropoietin (EPO) isoforms and methods for their production.
  • Technical Context: The technology concerns recombinant human erythropoietin, a biologic drug that stimulates red blood cell production and is a significant therapy for anemia, particularly in patients with chronic kidney disease.
  • Key Procedural History: The complaint is filed under the Biologics Price Competition and Innovation Act (BPCIA) and alleges that Defendant has failed to comply with the BPCIA’s statutory information exchange and negotiation procedures, known as the "patent dance." The complaint references the Federal Circuit's 2015 decision in Amgen v. Sandoz regarding the interpretation of these BPCIA provisions, particularly the timing of the notice of commercial marketing.

Case Timeline

Date Event
1983-12-13 ’349 Patent Priority Date
1989-10-13 ’298 Patent Priority Date
1998-05-26 ’349 Patent Issue Date
1999-01-05 ’298 Patent Issue Date
2010-03-23 BPCIA Enacted
2014-12 Defendant Submitted Biologic License Application (BLA) to FDA
2015-02-23 Defendant Notified Plaintiff that BLA was Accepted for Filing by FDA
2015-03-03 Defendant Provided a Copy of its BLA to Plaintiff
2015-04-08 Defendant Provided Purported Notice of Commercial Marketing to Plaintiff
2015-08-18 Plaintiff Sought to Engage in "Good-Faith Negotiations" with Defendant
2015-11-06 Complaint Filing Date

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

U.S. Patent No. 5,856,298 - “Erythropoietin Isoforms”

  • Issued January 5, 1999.

The Invention Explained

  • Problem Addressed: The patent’s background section explains that erythropoietin is a glycoprotein whose in vivo biological activity is dependent on its carbohydrate structure, particularly its sialic acid content (ʼ298 Patent, col. 1:29-37). Naturally occurring or recombinantly produced EPO is not a single uniform compound but rather a mixture of different "isoforms," each having a different level of sialylation and, consequently, different properties (ʼ298 Patent, col. 1:40-45). This heterogeneity makes it difficult to produce EPO with consistent and predictable biological activity.
  • The Patented Solution: The invention claims to solve this problem by providing isolated, specific EPO isoforms, each having a defined number of sialic acids per molecule, as well as pharmaceutical compositions comprising defined mixtures of these isoforms (ʼ298 Patent, Abstract). By separating EPO into distinct isoforms or creating defined mixtures, the invention purports to enable the creation of therapeutic products with more predictable and controlled biological activity profiles (ʼ298 Patent, col. 2:4-14). The specification describes techniques like isoelectric focusing to achieve this separation ('298 Patent, col. 5:64-6:3).
  • Technical Importance: This approach provided a method for characterizing and controlling the composition of a complex biologic drug, potentially allowing for fine-tuning of its therapeutic properties based on a key structural feature (sialic acid content).

Key Claims at a Glance

  • The complaint does not identify specific asserted claims but alleges infringement of "one or more claims" (Compl. ¶¶ 92, 98). Claim 1 is the first independent claim.
  • Claim 1 Elements:
    • An isolated biologically active erythropoietin isoform
    • having a single isoelectric point
    • and having a specific number of sialic acids per molecule, said number selected from the group consisting of 1-14,
    • and said isoform being the product of the expression of an exogenous DNA sequence in a non-human eucaryotic host cell.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 5,756,349 - “Production of Erythropoietin”

  • Issued May 26, 1998.

The Invention Explained

  • Problem Addressed: The patent background describes the significant therapeutic potential of EPO but notes the difficulty in obtaining sufficient quantities of the pure, active protein from natural sources like human urine (ʼ349 Patent, col. 7:1-15). The problem was the lack of a method for large-scale, reliable production of biologically active, glycosylated human EPO needed for clinical and therapeutic use.
  • The Patented Solution: The invention provides a solution through recombinant DNA technology by creating specific vertebrate host cells (e.g., CHO cells) genetically engineered to produce human EPO ('349 Patent, Abstract). These cells, containing exogenous DNA encoding human EPO under the control of appropriate regulatory sequences, can be grown in culture to produce and secrete large quantities of biologically active, glycosylated EPO, overcoming the supply limitations of natural sources ('349 Patent, col. 10:29-43, col. 26:1-5).
  • Technical Importance: This invention was foundational for the commercial-scale production of recombinant EPO, enabling its development into a major biopharmaceutical product.

Key Claims at a Glance

  • The complaint does not identify specific asserted claims but alleges infringement of "one or more claims" (Compl. ¶ 104). Claim 1 is the first independent claim.
  • Claim 1 Elements:
    • Vertebrate cells which can be propagated in vitro
    • and which are capable upon growth in culture of producing erythropoietin in the medium of their growth in excess of 100 U of erythropoietin per 10⁶ cells in 48 hours as determined by radioimmunoassay,
    • said cells comprising non-human DNA sequences which control transcription of DNA encoding human erythropoietin.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

The "Hospira Epoetin Biosimilar Product," also referred to as "Hospira Epoetin" (Compl. ¶¶ 10, 37).

Functionality and Market Context

The accused product is a biosimilar version of Amgen’s EPOGEN® (epoetin alfa) (Compl. ¶ 37). The complaint alleges it is designed to copy and compete with EPOGEN® for treating anemia and that Hospira will instruct its administration for the same indications for which EPOGEN® is approved (Compl. ¶ 38). Hospira sought FDA approval for its product under the abbreviated BPCIA pathway, relying on the safety and efficacy data from Amgen's original EPOGEN® license (Compl. ¶¶ 10, 39). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or provide a detailed, element-by-element analysis of infringement for any asserted patent claim. It alleges infringement based on Hospira’s submission of its BLA to the FDA, an act which constitutes a statutory act of infringement under 35 U.S.C. § 271(e)(2)(C) if the product, once marketed, would infringe (Compl. ¶ 92). The complaint states that Amgen's ability to identify infringing processes is limited because Hospira has allegedly withheld manufacturing information required under the BPCIA (Compl. ¶¶ 12, 51).

'298 Patent Infringement Allegations

The complaint alleges that Hospira’s BLA submission for its biosimilar product is an act of infringement and that the future commercial manufacture, use, or sale of the product will also constitute infringement (Compl. ¶¶ 92, 98). The narrative theory suggests that because the accused product is a biosimilar version of EPOGEN®, it will necessarily be a composition containing erythropoietin isoforms with specific sialic acid content falling within the scope of the claims of the ʼ298 Patent. The complaint does not provide sufficient detail for analysis of how specific features of the accused product map to the claim limitations.

'349 Patent Infringement Allegations

The infringement theory for the ’349 Patent is that Hospira, in manufacturing its biosimilar product, has engaged in the use of the vertebrate cells claimed in the patent (Compl. ¶ 104). This allegation is made on information and belief, and the complaint notes that Hospira's manufacturing process is "still secret" because Hospira allegedly failed to make the required BPCIA disclosures (Compl. ¶ 51). The complaint does not provide sufficient detail for analysis of how Hospira’s specific manufacturing process infringes the claim limitations.

  • Identified Points of Contention:
    • Evidentiary Questions: The central contention appears to be factual and dependent on discovery. What evidence will emerge from Hospira’s BLA and manufacturing information regarding the specific characteristics of its production cell line and the final drug product?
    • Scope Questions: Do the vertebrate cells used in Hospira's manufacturing process meet the functional limitation of "producing... in excess of 100 U of erythropoietin per 10⁶ cells in 48 hours" as required by Claim 1 of the ’349 Patent? Does the final "Hospira Epoetin Biosimilar Product" constitute a composition of "isolated... isoform[s]" with the specific sialic acid counts recited in Claim 1 of the ’298 Patent?

V. Key Claim Terms for Construction

"erythropoietin isoform having a single isoelectric point" (from Claim 1 of the ’298 Patent)

  • Context and Importance: This term is central to defining the claimed composition. The scope of "single isoelectric point" will be critical, as biologic products often exhibit microheterogeneity. Practitioners may focus on this term because the dispute could turn on whether a product that resolves as one band on a standard isoelectric focusing gel, but may not be 100% chemically uniform, meets this limitation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent’s general description of separating a "mixture of isoforms" into its components may suggest that a "single" isoform is one that has been effectively isolated from other, different isoforms, allowing for some level of instrumental or process-related variability (ʼ298 Patent, col. 5:64–6:3).
    • Evidence for a Narrower Interpretation: The term "single" itself, along with figures showing discrete, well-separated bands (e.g., ʼ298 Patent, Fig. 1), could support a narrower construction requiring a high degree of purity and homogeneity for a given isoform preparation.

"producing... in excess of 100 U... per 10⁶ cells in 48 hours" (from Claim 1 of the ’349 Patent)

  • Context and Importance: This functional limitation defines the claimed cells by their productivity. The infringement analysis for the ’349 Patent will depend on whether Hospira’s manufacturing cell line meets this production rate threshold. The method and conditions for measuring this rate will likely be a point of dispute.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language itself does not specify the culture conditions (e.g., media, cell density, bioreactor type) under which the rate must be measured, potentially allowing for measurement under optimized conditions that favor higher production.
    • Evidence for a Narrower Interpretation: The specification provides examples of production rates from specific cell types under specific laboratory conditions (e.g., CHO cells producing at rates up to 18.2 U/ml) (ʼ349 Patent, col. 26:1-5). A party could argue that the claim should be interpreted in light of the conditions and results disclosed in these examples.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that "Hospira will instruct or direct others to administer the Hospira Epoetin Biosimilar Product... in the same way that Amgen’s EPOGEN®... is administered," which may support a claim for induced infringement (Compl. ¶ 38).
  • Willful Infringement: The complaint does not use the word "willful" but does seek attorneys' fees for an "exceptional case" under 35 U.S.C. § 285 (Compl., Prayer for Relief ¶ L). The complaint alleges that Amgen disclosed the patents-in-suit to Hospira as part of the BPCIA process, establishing pre-suit knowledge (Compl. ¶ 89).

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

  • A central issue will be one of evidentiary proof: As this case proceeds through discovery, what will Hospira’s confidential manufacturing information and product characterization data reveal about its production cells and the final biosimilar product? The resolution of the infringement claims depends almost entirely on this yet-undisclosed technical evidence.
  • A key question of functional scope will be whether Hospira's manufacturing process uses "vertebrate cells" that meet the specific productivity threshold ("in excess of 100 U") defined in Claim 1 of the '349 patent under relevant testing conditions.
  • An overarching question will be the procedural impact of the BPCIA: How will the court treat Hospira’s alleged non-compliance with the BPCIA’s "patent dance" provisions, and how will that conduct, viewed through the lens of recent Federal Circuit precedent, shape the course of the litigation and the availability of certain remedies?