DCT

1:24-cv-00005

Alexion Pharma Inc v. Samsung Bioepis Co Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00005, D. Del., 01/03/2024
  • Venue Allegations: Venue is alleged to be proper because the defendant is a foreign corporation, which may be sued in any judicial district, and because it has allegedly transacted business in Delaware.
  • Core Dispute: Plaintiff alleges that Defendant's planned eculizumab biosimilar product, SB12, will infringe six U.S. patents covering the eculizumab antibody, its pharmaceutical compositions, and methods of its therapeutic use.
  • Technical Context: The technology involves a humanized monoclonal antibody, eculizumab (SOLIRIS®), which inhibits the complement protein C5 to treat rare autoimmune disorders such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).
  • Key Procedural History: This action was filed under the Biologics Price Competition and Innovation Act (BPCIA) following Defendant's submission of an abbreviated Biologics License Application (aBLA) for its biosimilar product and its subsequent refusal to participate in the BPCIA's information exchange process, known as the "patent dance." Defendant has filed inter partes review (IPR) petitions at the U.S. Patent and Trademark Office challenging the validity of five of the six asserted patents, indicating a parallel validity dispute outside of this litigation.

Case Timeline

Date Event
2006-03-15 Priority Date for ’149, ’880, ’504, ’189, and ’809 Patents
2008-11-10 Priority Date for ’176 Patent
2016-09-20 U.S. Patent No. 9,447,176 Issues
2017-08-01 U.S. Patent No. 9,718,880 Issues
2017-08-08 U.S. Patent No. 9,725,504 Issues
2017-08-15 U.S. Patent No. 9,732,149 Issues
2019-08-07 Defendant initiates Phase 3 study for SB12
2020-03-17 U.S. Patent No. 10,590,189 Issues
2020-07-07 U.S. Patent No. 10,703,809 Issues
2023-05-18 IPR petition filed against the ’149 Patent
2023-05-31 IPR petitions filed against the ’880 and ’504 Patents
2023-06-16 IPR petitions filed against the ’189 and ’809 Patents
2023-07-07 Defendant submits aBLA for SB12 on or before this date
2023-07-07 Defendant provides Notice of Commercial Marketing to Plaintiff
2024-01-03 Complaint Filing Date

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

U.S. Patent No. 9,732,149 - "Treatment of Paroxysmal Nocturnal Hemoglobinuria Patients by an Inhibitor of Complement"

The Invention Explained

  • Problem Addressed: The patents in this family address paroxysmal nocturnal hemoglobinuria (PNH), an acquired hematologic disease resulting from mutations that leave blood cells susceptible to destruction by the body's own complement system, a part of the immune system. This destruction, known as intravascular hemolysis, leads to anemia and other severe clinical consequences (Compl. ¶16; ’189 Patent, col. 1:32-51).
  • The Patented Solution: The invention is a specific humanized monoclonal antibody called eculizumab that binds to the human complement protein C5. This binding inhibits the cleavage of C5, which in turn blocks the formation of the "terminal complement complex" that would otherwise destroy the patient's red blood cells. The ’149 Patent specifically claims the antibody molecule itself by reciting the exact amino acid sequences of its heavy and light chains (’149 Patent, Claim 1; ’189 Patent, col. 8:56-62).
  • Technical Importance: The invention provided a first-in-class therapy that directly targets the mechanism of cell destruction in PNH, offering a way to manage a rare and life-threatening disorder for which there were previously no effective treatments to reduce hemolysis (Compl. ¶16; ’189 Patent, col. 1:61-64).

Key Claims at a Glance

  • The complaint asserts independent Claim 1 (’149 Patent, Claim 1; Compl. ¶36).
  • Claim 1 requires:
    • An antibody that binds C5
    • comprising a heavy chain consisting of SEQ ID NO: 2
    • and a light chain consisting of SEQ ID NO: 4.
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 9,718,880 - "Treatment of Paroxysmal Nocturnal Hemoglobinuria Patients by an Inhibitor of Complement"

The Invention Explained

  • Problem Addressed: As described above, the patent addresses the need for an effective treatment for PNH to control hemolysis and its clinical consequences (’189 Patent, col. 1:32-51).
  • The Patented Solution: This patent claims a specific pharmaceutical composition containing the eculizumab antibody (identified by its heavy and light chain sequences). The claim recites a sterile, preservative-free, 300 mg single-use dosage form comprising 30 mL of a 10 mg/mL antibody solution, providing a stable and clinically suitable formulation for administration to PNH patients (’880 Patent, Claim 1; Compl. ¶37).
  • Technical Importance: Defining a specific, stable, and clinically appropriate pharmaceutical formulation is a critical step in transforming a therapeutic antibody into a safe and effective commercial drug product for patient use (Compl. ¶37).

Key Claims at a Glance

  • The complaint asserts independent Claim 1 (’880 Patent, Claim 1; Compl. ¶37).
  • Claim 1 requires:
    • A pharmaceutical composition for use in treating a patient afflicted with paroxysmal nocturnal hemoglobinuria (PNH)
    • wherein the composition is sterile, preservative free, 300 mg single-use dosage form comprising 30 ml of a 10 mg/ml antibody solution
    • wherein the antibody comprises a heavy chain consisting of SEQ ID NO: 2 and a light chain consisting of SEQ ID NO: 4.
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 9,725,504 - "Treatment of Paroxysmal Nocturnal Hemoglobinuria Patients by an Inhibitor of Complement"

  • Technology Synopsis: This patent claims a method of treating PNH. The claimed solution involves administering a pharmaceutical composition containing the specific eculizumab antibody (identified by SEQ ID NOs: 2 and 4) to a patient suffering from the disease (Compl. ¶38).
  • Asserted Claims: Independent Claim 1 (Compl. ¶38).
  • Accused Features: Plaintiff alleges Defendant will induce infringement by seeking FDA approval for a product label that instructs physicians and patients to use SB12 to treat PNH, thereby practicing the claimed method (Compl. ¶107, 124).

U.S. Patent No. 10,590,189 - "Treatment of Paroxysmal Nocturnal Hemoglobinuria Patients by an Inhibitor of Complement"

  • Technology Synopsis: This patent claims a method of treating PNH by administering a pharmaceutical composition containing the specific eculizumab antibody. The method is further limited by the specific formulation of the composition, which must be a single-unit dosage form of 300 mg of the antibody in 30 mL of a sterile, preservative-free solution (Compl. ¶39).
  • Asserted Claims: Independent Claim 1 (Compl. ¶39).
  • Accused Features: Plaintiff alleges Defendant will induce infringement through its product label, which is expected to instruct users to administer SB12 in a manner that performs the claimed treatment method (Compl. ¶138, 155).

U.S. Patent No. 10,703,809 - "Treatment of Paroxysmal Nocturnal Hemoglobinuria Patients by an Inhibitor of Complement"

  • Technology Synopsis: This patent claims a method of treating PNH that specifies the route of administration. The method comprises intravenously administering the eculizumab antibody (identified by SEQ ID NOs: 2 and 4) to a patient with PNH (Compl. ¶40).
  • Asserted Claims: Independent Claim 1 (Compl. ¶40).
  • Accused Features: Plaintiff alleges Defendant will induce infringement through its product labeling and marketing, which are expected to direct intravenous administration of SB12 for the treatment of PNH (Compl. ¶169, 186).

U.S. Patent No. 9,447,176 - "Methods and Compositions for Treating Complement-Associated Disorders"

  • Technology Synopsis: This patent claims a method for treating a different condition, atypical hemolytic uremic syndrome (aHUS). The method requires intravenously administering eculizumab to a patient according to a specific two-stage dosing schedule: an initial phase of at least 600 mg once per week for four weeks, followed by a maintenance phase of at least 900 mg every two weeks (Compl. ¶41).
  • Asserted Claims: Independent Claim 1 (Compl. ¶41).
  • Accused Features: Plaintiff alleges Defendant will induce infringement because it is seeking FDA approval for SB12 to treat aHUS in addition to PNH, and its product label will allegedly instruct physicians to follow the claimed dosing schedule (Compl. ¶43, 200).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant's SB12, a proposed biosimilar to Plaintiff's SOLIRIS® (eculizumab) product (Compl. ¶2, 19).

Functionality and Market Context

SB12 is alleged to be a human monoclonal antibody that functions by binding to the C5 complement protein to inhibit the complement pathway (Compl. ¶16, 45). The complaint alleges that to be approved by the FDA as a biosimilar, SB12 must be "highly similar" to SOLIRIS® with "no clinically meaningful difference" in safety, purity, and potency (Compl. ¶45, 61). It further cites a finding from the European Medicines Agency that a European version of the product has an "identical primary [amino acid] sequence" to SOLIRIS® (Compl. ¶46, 62). Defendant is seeking FDA approval to market SB12 in the United States for treating PNH and aHUS and has provided Plaintiff with a 180-day notice of commercial marketing, signaling its intent to launch upon approval (Compl. ¶28, 43).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

'149 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An antibody that binds C5 The SB12 product is a biosimilar to eculizumab and allegedly binds to C5 to achieve its therapeutic effect. ¶45 ’189 Patent, col. 8:56-62
comprising a heavy chain consisting of SEQ ID NO: 2 The SB12 product must be "highly similar" to eculizumab to qualify as a biosimilar and is alleged to have an identical primary amino acid sequence. ¶45, 46, 61-62 ’189 Patent, col. 31:12-33:4
and a light chain consisting of SEQ ID NO: 4. The SB12 product must be "highly similar" to eculizumab to qualify as a biosimilar and is alleged to have an identical primary amino acid sequence. ¶45, 46, 61-62 ’189 Patent, col. 33:32-34:14

'880 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition for use in treating a patient afflicted with paroxysmal nocturnal hemoglobinuria (PNH) Defendant is seeking FDA approval for SB12 for the treatment of PNH. ¶73 ’189 Patent, col. 1:32-35
wherein the composition is sterile, preservative free, 300 mg single-use dosage form comprising 30 ml of a 10 mg/ml antibody solution The SB12 product is alleged to be a biosimilar to SOLIRIS® and is expected to be supplied in a dosage form that infringes, either literally or under the doctrine of equivalents. ¶2, 73, 75 ’189 Patent, col. 14:25-31
wherein the antibody comprises a heavy chain consisting of SEQ ID NO: 2 and a light chain consisting of SEQ ID NO: 4. The antibody in the SB12 product is alleged to have an amino acid sequence identical to eculizumab. ¶75-76 ’189 Patent, col. 31:12-34:14

Identified Points of Contention

  • Scope Questions: The core of the dispute for the composition patents (’149 and ’880) may turn on the scope of the term "consisting of." A primary question will be whether SB12's antibody has an amino acid sequence identical to that recited in the claims, or if it has minor variations that would place it outside the literal scope of "consisting of," potentially shifting the analysis to the doctrine of equivalents.
  • Technical Questions: A key evidentiary question, arising from Defendant's refusal to provide its aBLA, is what proof Plaintiff can adduce that SB12's final approved product will meet the specific claim limitations. For the ’880 Patent, what evidence does the complaint provide that the SB12 product will be formulated in the specific "300 mg single-use dosage form comprising 30 ml of a 10 mg/ml" solution as claimed? For the method-of-use patents, the dispute will likely focus on whether the instructions on Defendant's FDA-approved label will direct users to perform all steps of the claimed methods for the specified indications.

V. Key Claim Terms for Construction

  • The Term: "consisting of"
  • Context and Importance: This term, used in the independent claims of the ’149 and ’880 patents to define the antibody's heavy and light chains, is a closed term of art in patent law that excludes any elements not specified. Its construction is critical because if Defendant's SB12 antibody contains even a single amino acid difference from SEQ ID NOs: 2 and 4, it would not literally infringe. Practitioners may focus on this term because the entire literal infringement case for the composition claims depends on establishing sequence identity, not just similarity.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party seeking a broader effective scope would not argue for a broader meaning of the term itself, but would point to extrinsic evidence, such as the BPCIA's "highly similar" standard and the EMA's alleged finding of an "identical primary [amino acid] sequence" (Compl. ¶46), to argue that the accused product factually meets the strict limitation.
    • Evidence for a Narrower Interpretation: The patent specification provides strong support for a narrow, literal interpretation by repeatedly and explicitly defining the antibody by its exact sequences. The detailed description states that in certain embodiments, "the antibody that binds C5 or an active antibody fragment thereof comprises a heavy chain and a light chain, wherein the heavy chain consists of SEQ ID NO: 2 and the light chain consists of SEQ ID NO: 4" (’189 Patent, col. 14:63-67). This explicit recitation reinforces that the invention is the specific molecule defined by those sequences and nothing else.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of infringement for the method of treatment patents (’504, ’189, ’809, and ’176). The basis is Defendant's alleged intent to seek FDA approval for a product label that will instruct and encourage physicians and patients to administer SB12 for the claimed indications (PNH and aHUS) using the claimed methods, including intravenous administration and specific dosing schedules (Compl. ¶107, 138, 169, 200).
  • Willful Infringement: Plaintiff alleges willful infringement based on Defendant's pre-suit knowledge of the asserted patents. This knowledge is allegedly evidenced by Defendant's filing of IPR petitions with the USPTO to invalidate five of the asserted patents months before the complaint was filed, as well as by correspondence between counsel (Compl. ¶50, 80, 111, 142, 173, 204).

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

  • A core issue will be one of evidentiary proof under the BPCIA framework: Given Defendant's refusal to provide its confidential aBLA, can Plaintiff plausibly allege infringement based on the statutory requirement for biosimilarity and extrinsic evidence (such as foreign regulatory findings), particularly for claims that require sequence identity via "consisting of" language?
  • A second key question will be one of claim scope versus product labeling for induced infringement: For the method of treatment patents, the dispute will center on whether the final, FDA-approved label for SB12 will contain instructions that map precisely onto every step of the claimed methods—including specific indications, routes of administration, and dosing schedules—or if there will be a mismatch sufficient to avoid inducement.
  • A significant procedural question will be the interplay between this district court action and the parallel IPR proceedings: The ongoing challenges to the validity of five of the six asserted patents at the USPTO will loom over this case, raising the possibility of a stay and influencing case strategy and potential settlement discussions.