DCT

1:17-cv-00546

Amgen Inc v. Coherus Biosciences Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00546, D. Del., 05/10/2017
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because the Defendant, Coherus Biosciences Inc., is a Delaware corporation that has availed itself of the rights and benefits of Delaware law.
  • Core Dispute: Plaintiff alleges that Defendant's proposed biosimilar of NEULASTA® (pegfilgrastim) will be manufactured using a process that infringes a patent related to methods for purifying proteins using a dual-salt solution in hydrophobic interaction chromatography.
  • Technical Context: The technology concerns a key step in the commercial-scale manufacturing of biologic drugs, where improving the efficiency and capacity of protein purification columns can provide significant cost and time advantages.
  • Key Procedural History: This action arises under the Biologics Price Competition and Innovation Act (BPCIA) following Defendant's submission of an abbreviated Biologic License Application (aBLA) for its pegfilgrastim product. The complaint states that the parties engaged in the statutory information exchange, which culminated in an agreement to include the patent-in-suit in an immediate infringement action.

Case Timeline

Date Event
2004-01-30 '707 Patent Priority Date
2012-09-25 '707 Patent Issue Date
2016-08-09 Coherus submits its aBLA to the FDA
2016-10-06 Coherus receives notice of FDA acceptance for aBLA review
2016-10-01 BPCIA information exchange begins
2017-04-01 Parties agree to include '707 Patent in infringement action
2017-05-10 Complaint Filing Date

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

U.S. Patent No. 8,273,707 - "PROCESS FOR PURIFYING PROTEINS"

  • Patent Identification: U.S. Patent No. 8,273,707, "PROCESS FOR PURIFYING PROTEINS", issued September 25, 2012. (Compl. ¶41).

The Invention Explained

  • Problem Addressed: In developing commercial processes for producing therapeutic proteins, increasing the efficiency of intermediate purification steps is highly desirable. A specific challenge is to increase the load capacity of a hydrophobic interaction chromatography (HIC) column without compromising the quality of the separated protein, which can occur when using high salt concentrations that may destabilize the protein or cause aggregation. (’707 Patent, col. 2:48-62; col. 4:39-47).
  • The Patented Solution: The patent describes a process that uses a combination of two different salts with different lyotropic values to prepare the protein solution before loading it onto an HIC column. This dual-salt approach is purported to increase the "dynamic capacity" of the column—the amount of protein it can purify without significant loss—compared to using either salt individually. (’707 Patent, Abstract; col. 2:9-16). This increased capacity can be achieved using lower overall salt concentrations, which aids in maintaining protein stability. (’707 Patent, col. 2:12-16).
  • Technical Importance: This method provides a way to improve the efficiency of commercial manufacturing for proteins, potentially reducing the number of purification cycles, and therefore the time and cost, required to purify a given batch of a biologic drug. (’707 Patent, col. 2:42-47).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 and dependent claims 2, 3, 4, and 7. (Compl. ¶50).
  • Independent Claim 1 of the ’707 Patent recites the following essential elements:
    • A process for purifying a protein on a hydrophobic interaction chromatography (HIC) column such that the dynamic capacity of the column is increased for the protein.
    • The process comprises steps of:
      • mixing a preparation containing the protein with a combination of a first salt and a second salt,
      • loading the mixture onto an HIC column, and
      • eluting the protein.
    • The first and second salts are selected from specific pairs: (citrate and sulfate), (citrate and acetate), or (sulfate and acetate).
    • The concentration of each of the first and second salt in the mixture is between about 0.1 M and about 1.0 M.
      (’707 Patent, col. 15:8-18).
  • The complaint reserves the right to assert other claims. (Compl. ¶48).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the process by which Coherus manufactures its "Coherus Pegfilgrastim Product," a proposed biosimilar to Amgen’s NEULASTA®. (Compl. ¶¶ 9, 15, 44).

Functionality and Market Context

  • The Coherus product is a biologic medicine intended to treat neutropenia (a deficiency of white blood cells) in patients receiving chemotherapy. (Compl. ¶¶ 26-27). The infringement allegation centers on the purification step within the manufacturing process. (Compl. ¶50).
  • The complaint alleges that Coherus is seeking FDA approval for its product via the abbreviated BPCIA pathway, relying on Amgen's prior demonstration that NEULASTA® is "safe, pure, and potent" in order to "copy and compete with Amgen's NEULASTA®." (Compl. ¶¶ 31-33). The complaint alleges Coherus has a manufacturing agreement with KBI BioPharma, Inc. for "long-term manufacturing" of the product. (Compl. ¶16).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

Claim Chart Summary

  • The complaint does not contain a claim chart exhibit but provides a narrative infringement theory. The allegations are summarized below.

’707 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A process for purifying a protein on a hydrophobic interaction chromatography column... Coherus is alleged to practice a process for purifying a protein (pegfilgrastim) on a hydrophobic interaction chromatography column. ¶50 col. 4:52-58
...mixing a preparation containing the protein with a combination of a first salt and a second salt, In the Coherus process, a protein preparation is allegedly mixed with a combination of a first and second salt. ¶50 col. 2:1-3
...loading the mixture onto a hydrophobic interaction chromatography column, and The mixture containing protein and dual salts is allegedly loaded onto an HIC column. ¶50 col. 2:3-4
...eluting the protein, The protein is allegedly eluted from the column. ¶50 col. 2:8
...wherein the first and second salts are selected from the group consisting of citrate and sulfate, citrate and acetate, and sulfate and acetate, respectively, The combination of salts used in the Coherus process is alleged to be "the equivalent of one or more of the recited salt pairs." ¶50 col. 15:15-16
...and wherein the concentration of each of the first salt and the second salt in the mixture is between about 0.1 M and about 1.0. The concentration of each salt in the Coherus mixture allegedly "falls within the claimed range and/or is equivalent to a concentration within the claimed range." ¶50 col. 2:31-33

Identified Points of Contention

  • Scope Questions: A central dispute may arise from the complaint's repeated use of the term "equivalent." (Compl. ¶50). This raises the question of whether Coherus's process literally uses one of the three specific salt pairs recited in the claim, or if Amgen will need to prove infringement under the doctrine of equivalents by showing Coherus uses a different but equivalent combination.
  • Technical Questions: A key technical question, the answer to which is likely contained in confidential aBLA materials (Compl. ¶49), is the precise composition of the buffer salts used in Coherus's purification process. Further, the preamble's requirement that the process be one "such that the dynamic capacity of the column is increased" raises the evidentiary question of whether Coherus's process achieves this functional outcome relative to a single-salt baseline.

V. Key Claim Terms for Construction

The Term: "such that the dynamic capacity of the column is increased for the protein"

Context and Importance

  • This phrase appears in the preamble of claim 1. Practitioners may focus on this term because its interpretation as either a binding limitation or a non-limiting statement of purpose could be case-dispositive. If it is a limitation, Amgen must prove that Coherus's process not only meets the subsequent process steps but also achieves this specific functional result.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation (Non-limiting): A party could argue the phrase merely states the intended purpose or inherent result of performing the claimed steps (mixing specific salts, loading, eluting), and does not impose a separate, affirmative requirement of proof. The body of the claim recites a complete process, suggesting the preamble is introductory. (’707 Patent, col. 5:55-6:3).
  • Evidence for a Narrower Interpretation (Limiting): The patent repeatedly emphasizes this increase in dynamic capacity as the core of the invention. The title, abstract, and summary of the invention all highlight this functional benefit, which may suggest the phrase is definitional to the claimed process and necessary to distinguish it from the prior art. (’707 Patent, Title; Abstract; col. 2:40-42).

The Term: "a combination of a first salt and a second salt"

Context and Importance

  • This term is central to the invention. The dispute will likely turn on whether Coherus's accused process uses a "combination" that falls within the claim's scope, especially in light of the complaint's allegations of "equivalence." (Compl. ¶50).

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification describes the invention more generally as using two salts with "different lyotropic values." (’707 Patent, col. 2:1-4). This language could be used to argue for a broader understanding of what constitutes an infringing combination, particularly under the doctrine of equivalents.
  • Evidence for a Narrower Interpretation: Claim 1 is explicitly limited to three specific pairs of salts: (citrate and sulfate), (citrate and acetate), and (sulfate and acetate). (’707 Patent, col. 15:15-16). This express recitation could be argued to strictly define the scope of the claim, excluding all other combinations from literal infringement.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges that Coherus will induce infringement by "intentionally encouraging, aiding and abetting KBI's acts of direct infringement in manufacturing the Coherus Pegfilgrastim Product." (Compl. ¶19). This is based on a manufacturing agreement between Coherus and KBI BioPharma, Inc. (Compl. ¶16). The complaint alleges Coherus has knowledge of the '707 Patent from the BPCIA information exchange. (Compl. ¶¶ 19, 36, 62).

Willful Infringement

  • The complaint does not use the term "willful," but it does seek a declaration that the case is "exceptional" and an award of attorneys' fees under 35 U.S.C. § 285. (Prayer for Relief, ¶G). The basis for this may be Coherus’s alleged knowledge of the patent from the statutory BPCIA exchange prior to engaging in potentially infringing commercial manufacturing. (Compl. ¶¶ 19, 62).

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

  • A core issue will be one of evidentiary proof and equivalence: Given the confidentiality of Defendant's aBLA submission, a central question is whether the undisclosed details of its manufacturing process meet the specific limitations of Claim 1. The complaint’s reliance on the term "equivalent" suggests a primary dispute will be whether Coherus’s process infringes literally or, alternatively, under the doctrine of equivalents, which would require proof that any different salts used perform substantially the same function in substantially the same way to achieve the same result.
  • A second key issue will be one of claim construction: The case may turn on whether the preamble phrase "such that the dynamic capacity of the column is increased" is construed as a legally binding limitation. If the court finds it is limiting, Plaintiff would bear the additional burden of proving that Defendant's process achieves this specific functional outcome.
  • A final question will concern the scope of infringement: The litigation will likely examine whether Coherus’s actions in submitting its aBLA constitute an act of infringement under 35 U.S.C. § 271(e)(2)(C)(i), and whether its arrangements with its manufacturer create liability for direct infringement, induced infringement, and/or infringement based on the importation of a product made by a patented process under § 271(g).