DCT

1:20-cv-00804

Sanofi Aventis US LLC v. Apotex Corp

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Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-00804, D. Del., 08/30/2021
  • Venue Allegations: Venue is alleged based on Defendants' incorporation in Delaware, consent through participation in prior litigation in the district, and systematic business contacts within the state.
  • Core Dispute: Plaintiff alleges that Defendants' submission of applications to the FDA for approval of generic versions of the cancer drug JEVTANA® (cabazitaxel) constitutes an act of infringement of three patents covering methods of using the drug to treat prostate cancer.
  • Technical Context: The technology involves second-line chemotherapy regimens for metastatic castration-resistant prostate cancer, a field where extending patient survival after initial treatment failure is a primary clinical goal.
  • Key Procedural History: The asserted patents are the subject of ongoing consolidated litigation initiated in 2020. This follows prior litigation between the same parties over an earlier patent (U.S. Patent No. 5,847,170), where that patent was found infringed and not invalid. Additionally, U.S. Patent No. 8,927,592 was the subject of an inter partes review (IPR) proceeding initiated by Mylan, which resulted in the PTAB replacing original claims 27-30 with amended substitute claims 31-34, a decision affirmed by the Federal Circuit; the infringement allegations against the ’592 patent are directed to these amended claims.

Case Timeline

Date Event
2009-10-29 Priority Date for ’110, ’777, and ’592 Patents
2014-12-04 Apotex & Mylan send notice letters regarding ’592 Patent
2015-01-06 U.S. Patent No. 8,927,592 issues
2016-08-04 Sandoz sends notice letter regarding ’592 Patent
2017-09-18 Prior litigation bench trial begins regarding ’592 Patent
2020-03-10 U.S. Patent No. 10,583,110 issues
2020-05-28 Mylan sends notice letter regarding ’110 and ’777 Patents
2020-06-05 Plaintiff files suit against Mylan for infringement of ’110 Patent
2020-06-12 Plaintiff files suit against Apotex and Sandoz for infringement of ’110 Patent
2020-07-21 U.S. Patent No. 10,716,777 issues
2020-07-22 Plaintiff asserts ’777 Patent against Mylan
2020-07-31 Plaintiff asserts ’777 Patent against Apotex and Sandoz
2020-08-05 Actions consolidated in D. Del.
2020-08-05 Apotex sends notice letter regarding ’110 and ’777 Patents
2021-08-23 Certificate amending claims of ’592 Patent issues post-IPR
2021-08-30 Plaintiff files Second Amended Complaint

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

U.S. Patent No. 10,583,110 - "Antitumoral Use of Cabazitaxel"

Issued March 10, 2020

The Invention Explained

  • Problem Addressed: The patent describes a need for new therapeutic options for patients with advanced prostate cancer, particularly those whose cancer has progressed despite treatment with a taxane-based chemotherapy like docetaxel (’110 Patent, col. 2:19-29). Such patients have limited treatment alternatives and face poor prognoses.
  • The Patented Solution: The invention is a method of using the taxoid compound cabazitaxel to treat this specific patient population. The patent discloses that administering cabazitaxel in combination with prednisone and a specific premedication regimen was shown in a clinical trial to result in a statistically significant improvement in overall survival compared to a standard-of-care mitoxantrone regimen (’110 Patent, col. 11:40-54; Abstract).
  • Technical Importance: This method provided a clinically validated second-line treatment that extended life for patients with metastatic castration-resistant prostate cancer who had previously failed docetaxel therapy, addressing a significant unmet medical need (Compl. ¶92).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’110 Patent (Compl. ¶95). Independent claim 1 is central to the technology.
  • The essential elements of independent claim 1 are:
    • A method of increasing survival comprising administering to a patient in need thereof:
    • (1) cabazitaxel, or a hydrate of solvate thereof, as a new cycle every three weeks; and
    • (2) dexchlorpheniramine, dexamethasone, and an H2 antagonist;
    • wherein each premedication agent in (2) is administered prior to the cabazitaxel;
    • and wherein the patient has castration resistant metastatic prostate cancer that has progressed during or after treatment with docetaxel.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 10,716,777 - "Antitumoral Use of Cabazitaxel"

Issued July 21, 2020

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’110 Patent, this patent addresses the same technical problem: the need for an effective second-line therapy for patients with metastatic castration-resistant prostate cancer who have already been treated with a docetaxel-based regimen (’777 Patent, col. 2:21-30).
  • The Patented Solution: The invention is a method of treatment using cabazitaxel that was shown to increase survival in this patient population. The claims focus on a specific dosage range of cabazitaxel administered in combination with a premedication regimen that includes an H2 antagonist to manage hypersensitivity reactions, thereby enabling the safe and effective use of the drug (’777 Patent, col. 6:49-65; col. 11:40-48).
  • Technical Importance: The method provides a defined, clinically tested protocol for administering cabazitaxel that improves survival while managing known side effects, establishing a standard of care for this patient population (Compl. ¶115).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’777 Patent (Compl. ¶118). Independent claim 1 is representative.
  • The essential elements of independent claim 1 are:
    • A method of increasing survival comprising administering to a patient in need thereof:
    • a dose of 20 to 25 mg/m² of cabazitaxel, or a hydrate or solvate thereof;
    • in combination with an H₂ antagonist;
    • wherein the H₂ antagonist is administered to the patient prior to administering the dose of cabazitaxel;
    • and wherein the patient has castration resistant metastatic prostate cancer that has progressed during or after treatment with docetaxel.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 8,927,592 - "Antitumoral Use of Cabazitaxel"

Issued January 6, 2015

Technology Synopsis

This patent, which shares a common specification with the ’110 and ’777 patents, is also directed to methods of treating advanced prostate cancer with cabazitaxel. The asserted claims, which were added during an inter partes review, specifically recite a method of increasing survival by administering cabazitaxel with a three-part premedication regimen to patients previously treated with docetaxel (Compl. ¶64, 82).

Asserted Claims

The complaint alleges infringement of "one or more amended claims," referencing substitute claims 31-34 which replaced the original claims 27-30 (Compl. ¶64, 135). Claim 31 is the new independent claim.

Accused Features

The complaint alleges that Defendants' proposed product labels will instruct physicians to administer cabazitaxel in combination with prednisone and a premedication regimen including an antihistamine, a corticoid, and an H2 antagonist to the specified patient population, thereby inducing infringement of the amended claims (Compl. ¶137-141).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the proposed generic cabazitaxel injection products that are the subject of Abbreviated New Drug Application ("ANDA") No. 207736 filed by Apotex, ANDA No. 207381 filed by Mylan, and B2 New Drug Application ("NDA") No. 208715 filed by Sandoz (Compl. ¶10, 34, 50).

Functionality and Market Context

The products are generic versions of Plaintiff's JEVTANA® KIT, a chemotherapy drug for intravenous infusion (Compl. ¶1). The infringement allegations are not based on the composition of the drugs themselves, but on the proposed labeling that will accompany them. The complaint alleges that the proposed labeling for each Defendant's product will be "substantially identical to the JEVTANA® label" and will therefore instruct and encourage physicians to use the generic products in a manner that directly infringes the asserted method patents (Compl. ¶91, 114, 137). These instructions allegedly include administering the drug for the purpose of increasing survival, using a specific premedication regimen, and treating the specific patient population defined in the patent claims (Compl. ¶92-94, 115-117, 138-141).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

10,583,110 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of increasing survival... The proposed label will allegedly describe clinical study data showing cabazitaxel prolongs survival and instruct physicians to administer the drug for that purpose. ¶92 col. 11:40-48
...administering to a patient... (1) cabazitaxel... and (2) dexchlorpheniramine..., dexamethasone..., and an H2 antagonist... The proposed label will allegedly instruct premedication with an antihistamine (such as dexchlorpheniramine), a corticosteroid (such as dexamethasone), and an H2 antagonist. ¶94 col. 6:49-61
...each administered prior to the administration of said cabazitaxel... The proposed label will allegedly instruct physicians to premedicate at least 30 minutes prior to each dose of the drug. ¶94 col. 6:49-52
...wherein said patient has castration resistant metastatic prostate cancer that has progressed during or after treatment with docetaxel. The proposed label will allegedly state that the drug is indicated for the "treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen." ¶92 col. 2:23-29

10,716,777 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of increasing survival... The proposed label will allegedly describe clinical data showing increased survival and encourage administration for that purpose. ¶115 col. 11:40-48
...administering to a patient... a dose of 20 to 25 mg/m² of cabazitaxel... in combination with an H₂ antagonist... The proposed label will allegedly recommend a dose of 20 mg/m² or 25 mg/m² and instruct premedication with an H2 antagonist. ¶116, 117 col. 6:15-17
...wherein the H₂ antagonist is administered to the patient prior to administering the dose of cabazitaxel... The proposed label will allegedly instruct physicians to premedicate at least 30 minutes prior to each dose. ¶117 col. 6:49-52
...wherein said patient has castration resistant metastatic prostate cancer that has progressed during or after treatment with docetaxel. The proposed label will allegedly state this specific indication for the drug. ¶115 col. 2:21-30

Identified Points of Contention

  • Scope Questions: A potential issue is whether the instructions on the proposed generic labels will be construed as actively inducing infringement of all limitations. Defendants may argue that the labels permit non-infringing uses or that they do not require a physician to administer the drug for the specific claimed purpose of "increasing survival," but rather simply for "treatment."
  • Technical Questions: The case raises the legal and factual question of divided infringement, particularly for claims that require administration of prednisone (such as in the ’592 patent). The complaint alleges that physicians "direct and control" every step, including the oral administration of prednisone by the patient (Compl. ¶142). A central question will be whether the evidence supports a finding that a single actor—the physician—can be held responsible for all steps of the claimed method.

V. Key Claim Terms for Construction

"increasing survival"

  • Context and Importance: This term defines the purpose and outcome of the claimed method. Its construction is critical because the infringement case relies on the allegation that Defendants' labels instruct use for this purpose. Practitioners may focus on this term because Defendants could argue that a product label's description of clinical trial results does not constitute an instruction to achieve that same statistical outcome in every patient, potentially creating a gap between the label's language and the claim's requirement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification repeatedly links the use of cabazitaxel in the target population to the observed survival benefit in the TROPIC clinical trial, suggesting the term encompasses the intended clinical goal of the therapy (’110 Patent, col. 11:40-54).
    • Evidence for a Narrower Interpretation: The detailed description quantifies the survival benefit with specific hazard ratios and median survival months (’110 Patent, col. 11:40-48). A party could argue that "increasing survival" should be limited to achieving a statistically significant result comparable to that disclosed in the specification.

"in combination with"

  • Context and Importance: This term, appearing in the claims of the ’777 and ’592 patents, defines the relationship between the administration of cabazitaxel and other required agents (e.g., prednisone, H2 antagonist). Its interpretation is key to determining whether the steps must be performed in a specific sequence or time frame to infringe.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: In a general sense, the term could be read to cover drugs that are part of the same overall treatment plan, even if not administered simultaneously.
    • Evidence for a Narrower Interpretation: The claims themselves often provide context. For example, claim 1 of the ’777 patent recites administration "in combination with an H₂ antagonist" and then further requires that the H2 antagonist be "administered to the patient prior to administering the dose of cabazitaxel," suggesting "in combination with" requires a close temporal and functional relationship as part of a single administration event.

VI. Other Allegations

  • Indirect Infringement: The core of the complaint is inducement of infringement. It is alleged that by submitting ANDAs/NDAs with proposed labeling that is substantially identical to the JEVTANA® label, Defendants are encouraging and instructing physicians to practice the patented methods. The specific facts alleged are the contents of the label, which purportedly detail the specific patient population, premedication steps, and dosages recited in the claims (Compl. ¶96, 119, 144).
  • Willful Infringement: While the complaint does not include a separate count for willful infringement, it alleges facts that may support such a finding or a finding of an exceptional case. The complaint establishes that each Defendant had pre-suit knowledge of the patents through notice letters and prior litigation conduct (Compl. ¶11, 35, 51, 88, 111, 134).

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

  • A central issue will be one of induced infringement: will the Defendants' proposed product labels be found to contain instructions that are specific enough to encourage and lead prescribing physicians to perform every step of the asserted method claims, including administration for the express purpose of "increasing survival"?
  • A key evidentiary question will be one of divided infringement: can Plaintiff prove that a single actor, the prescribing physician, "directs or controls" all steps of the claimed methods, including those steps performed by others (such as a nurse administering an infusion or a patient taking an oral medication), such that infringement can be attributed to one party?
  • The case may also present questions regarding the impact of the IPR proceeding on the ’592 patent, specifically whether the amendment of the claims creates any intervening rights for the Defendants or introduces new arguments related to claim scope and validity based on the prosecution history of the reexamination.