DCT

1:20-cv-00431

Ferring Pharma Inc v. Fresenius Kabi USA LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-00431, D. Del., 04/14/2021
  • Venue Allegations: Venue is based on Defendant's incorporation in the state of Delaware, establishing residency within the judicial district.
  • Core Dispute: Plaintiffs allege that Defendant's submission of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiffs' prostate cancer drug FIRMAGON® (degarelix) constitutes an act of infringement of eight U.S. patents related to methods of using and manufacturing degarelix.
  • Technical Context: The dispute centers on a gonadotrophin-releasing hormone (GnRH) antagonist therapy used for androgen deprivation in patients with advanced prostate cancer, a significant market in oncology therapeutics.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 211999 with a Paragraph IV certification, asserting non-infringement or invalidity of Plaintiffs' patents. Plaintiffs received Defendant’s Notice Letter on February 10, 2020. The complaint notes that a Fresenius entity previously filed an opposition to a European counterpart of the ’081 patent, suggesting a history of challenges to this patent family.

Case Timeline

Date Event
2008-02-11 Earliest Priority Date for ’359, ’085, ’081, ’999, ’398, ’739, and ’870 Patents
2008-12-24 FDA Approval of FIRMAGON® (NDA No. 022201)
2009-04-24 Earliest Priority Date for ’938 Patent
2014-09-09 U.S. Patent No. 8,828,938 Issues
2014-09-23 U.S. Patent No. 8,841,081 Issues
2015-12-22 Fresenius Kabi Deutschland GmbH files Opposition to European counterpart of ’081 Patent
2016-08-16 U.S. Patent No. 9,415,085 Issues
2017-02-28 U.S. Patent No. 9,579,359 Issues
2018-01-30 U.S. Patent No. 9,877,999 Issues
2020-02-10 Defendant sends Paragraph IV Notice Letter to Plaintiffs
2020-06-30 U.S. Patent No. 10,695,398 Issues
2020-08-04 U.S. Patent No. 10,729,739 Issues
2021-04-13 U.S. Patent No. 10,973,870 Issues
2021-04-14 Plaintiffs file Third Amended Complaint

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

U.S. Patent No. 9,579,359 - "Method of Treating Prostate Cancer with GnRH Antagonist"

  • Patent Identification: U.S. Patent No. 9,579,359, "Method of Treating Prostate Cancer with GnRH Antagonist," issued February 28, 2017.

The Invention Explained

  • Problem Addressed: Standard hormonal therapies for prostate cancer using gonadotrophin-releasing hormone (GnRH) agonists can cause an initial, dangerous "testosterone spike" or "flare reaction" that can temporarily worsen the cancer and its symptoms before therapeutic effects begin (U.S. Patent No. 10,729,739, col. 2:1-24).
  • The Patented Solution: The invention uses a GnRH antagonist, degarelix, which avoids the testosterone spike. The patent claims a specific dosing regimen consisting of a higher initial "loading" dose followed by lower, periodic "maintenance" doses to rapidly achieve and sustain testosterone suppression at medically castrate levels (Compl. ¶28; ’739 Patent, col. 4:40-56).
  • Technical Importance: This method provides rapid and sustained androgen deprivation for prostate cancer patients without the initial clinical aggravation and potential complications associated with GnRH agonist therapies (Compl. ¶28).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶¶28, 62).
  • The essential elements of claim 1 are:
    • A method of treating prostate cancer in a subject with a reduced likelihood of causing a testosterone spike or other GnRH agonist side-effect comprising:
    • administering an initial dose of 160-320 mg of degarelix to the subject, wherein the initial dose is administered as two subcutaneous injections; and
    • administering a maintenance dose of 60-160 mg of degarelix to the subject once every 20-36 days thereafter,
    • wherein the maintenance dose results in a testosterone suppression below 0.5 ng/mL.
  • The complaint notes the Detailed Statement from Defendant did not assert non-infringement of claims 1-5, 7, and 9-13, which may suggest Plaintiffs intend to pursue these as well (Compl. ¶62).

U.S. Patent No. 9,415,085 - "Method of Treating Prostate Cancer with GnRH Antagonist"

  • Patent Identification: U.S. Patent No. 9,415,085, "Method of Treating Prostate Cancer with GnRH Antagonist," issued August 16, 2016.

The Invention Explained

  • Problem Addressed: The patent family addresses concerns that androgen deprivation therapy using GnRH agonists may be associated with an increased risk of cardiovascular (CV) events, particularly in patients with pre-existing cardiovascular disease (U.S. Patent No. 10,695,398, col. 4:5-14).
  • The Patented Solution: The invention claims a method of treating a specific sub-population of prostate cancer patients: those with a history of at least one cardiovascular event. Administering degarelix to this group is claimed to decrease the frequency of additional cardiovascular events when compared to treatment with a GnRH agonist (’398 Patent, Abstract).
  • Technical Importance: This method provides a tailored, potentially safer therapeutic option for a high-risk patient population that has both advanced prostate cancer and a history of cardiovascular disease (’398 Patent, col. 4:15-25).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶32).
  • The essential elements of claim 1 are:
    • A method of treating prostate cancer in a subject, comprising:
    • selecting a subject with a history of at least one cardiovascular event and prostate cancer;
    • administering degarelix to the subject, wherein administration of degarelix to the subject decreases the frequency of an additional cardiovascular event in the subject as compared to the frequency of an additional cardiovascular event upon treatment with a GnRH agonist in a subject with a history of at least one cardiovascular event,
    • wherein the at least one cardiovascular event is chosen from myocardial infarction, ischemic heart disease, ischemic stroke, hemorrhagic stroke, and other arterial thrombotic/embolic events.
  • The complaint does not explicitly reserve the right to assert dependent claims for the ’085 Patent.

Multi-Patent Capsule: U.S. Patent No. 8,841,081 - "Method of Treating Metastatic Stage Prostate Cancer"

  • Patent Identification: U.S. Patent No. 8,841,081, "Method of Treating Metastatic Stage Prostate Cancer," issued September 23, 2014.
  • Technology Synopsis: The patent addresses treatment for metastatic prostate cancer. The claimed solution is a method that involves identifying a subject with this stage of cancer by measuring baseline serum alkaline phosphatase (S-ALP) and prostate-specific antigen (PSA) levels, and then reducing the S-ALP level by administering a specific initial and maintenance dosing regimen of degarelix (Compl. ¶103; ’081 Patent, Abstract).
  • Asserted Claims: Independent claims 1 and 15 are identified in the complaint (Compl. ¶¶103, 36).
  • Accused Features: The complaint alleges infringement based on the inducement of physicians to treat patients with advanced/metastatic prostate cancer using the ANDA product, which will involve monitoring biomarkers like S-ALP and PSA as described in medical literature associated with the pivotal clinical trial for degarelix (Compl. ¶¶119-120).

Multi-Patent Capsule: U.S. Patent No. 9,877,999 - "Method for Treating Metastatic Stage Prostate Cancer"

  • Patent Identification: U.S. Patent No. 9,877,999, "Method for Treating Metastatic Stage Prostate Cancer," issued January 30, 2018.
  • Technology Synopsis: This patent addresses treatment for a specific subset of patients: those with metastatic prostate cancer who also have an S-ALP level above the normal range. The method involves testing both S-ALP and PSA, selecting the patient for treatment if S-ALP is elevated and PSA is greater than or equal to 50 ng/mL, and then administering a specific degarelix dosing regimen to reduce the S-ALP level (Compl. ¶139).
  • Asserted Claims: The complaint identifies five independent claims, with claim 15 provided as an example (Compl. ¶139).
  • Accused Features: The complaint alleges infringement by inducing physicians to follow the proposed package insert and review related literature, which will lead them to test for S-ALP and PSA and administer the ANDA product to the specified patient population, thereby reducing their S-ALP levels (Compl. ¶¶155-156).

Multi-Patent Capsule: U.S. Patent No. 8,828,938 - "Method for the Manufacture of Degarelix"

  • Patent Identification: U.S. Patent No. 8,828,938, "Method for the Manufacture of Degarelix," issued September 9, 2014.
  • Technology Synopsis: The patent addresses risks associated with prior art methods of synthesizing degarelix, which used toxic reagents. The claimed solution is a method of manufacturing degarelix with a low level of a specific impurity (≤ 0.3% by weight) using a solid-phase peptide synthesis process that employs an Fmoc protecting group and a specific organic base (piperidine or C-alkyl substituted piperidine) for its removal (Compl. ¶¶42, 175-177).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶42).
  • Accused Features: The complaint alleges that Defendant's synthesis of the degarelix active pharmaceutical ingredient for its ANDA Product will infringe because the patented method is the only commercially viable way to produce degarelix of sufficient purity for pharmaceutical applications (Compl. ¶¶178, 191).

Multi-Patent Capsule: U.S. Patent No. 10,695,398 - "Method of Treating Prostate Cancer with GnRH Antagonist"

  • Patent Identification: U.S. Patent No. 10,695,398, "Method of Treating Prostate Cancer with GnRH Antagonist," issued June 30, 2020.
  • Technology Synopsis: This patent, similar to the ’085 patent, is directed to treating prostate cancer patients who have a history of cardiovascular events. The claimed method involves selecting such a subject and administering degarelix, which is asserted to diminish the risk of an additional cardiovascular event compared to treatment with a GnRH agonist (Compl. ¶45).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶45).
  • Accused Features: Infringement is alleged based on the inducement of physicians, via the proposed product insert, to administer the ANDA product to the broad population of advanced prostate cancer patients, which necessarily includes the claimed sub-population with a history of cardiovascular events (Compl. ¶¶202-203).

Multi-Patent Capsule: U.S. Patent No. 10,729,739 - "Method of Treating Prostate Cancer with GnRH Antagonist"

  • Patent Identification: U.S. Patent No. 10,729,739, "Method of Treating Prostate Cancer with GnRH Antagonist," issued August 4, 2020.
  • Technology Synopsis: This patent, similar to the ’359 patent, claims a method of treating prostate cancer while reducing the likelihood of a testosterone spike. It specifies a particular degarelix dosing regimen (initial dose of 160-320 mg via two injections, then maintenance doses of 60-160 mg every 20-36 days) for a duration of 364 days while maintaining testosterone suppression (Compl. ¶49).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶49).
  • Accused Features: The complaint alleges infringement by inducement, as the Defendant's proposed product insert will direct physicians and patients to use the ANDA product according to the claimed dosing regimen and duration (Compl. ¶¶213-214).

Multi-Patent Capsule: U.S. Patent No. 10,973,870 - "Method of Treating Prostate Cancer with GnRH Antagonist"

  • Patent Identification: U.S. Patent No. 10,973,870, "Method of Treating Prostate Cancer with GnRH Antagonist," issued April 13, 2021.
  • Technology Synopsis: This patent claims a method of treating locally advanced prostate cancer. The method involves choosing a degarelix dosing regimen over a GnRH agonist treatment specifically to decrease the likelihood of developing musculoskeletal or connective tissue disorders, followed by administering the specified degarelix dosing regimen (Compl. ¶53).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶53).
  • Accused Features: Infringement is alleged based on inducement, as the Defendant's proposed product insert, which will be substantially similar to the FIRMAGON® insert containing information on side effects, will encourage physicians to choose the ANDA product for the claimed purpose (Compl. ¶¶224-225).

III. The Accused Instrumentality

  • Product Identification: Defendant's Abbreviated New Drug Application (“ANDA”) No. 211999 product, which is a generic version of FIRMAGON® (degarelix for injection) (Compl. ¶2).
  • Functionality and Market Context: The accused product is a sterile, lyophilized powder containing degarelix, a GnRH antagonist, for subcutaneous injection after reconstitution (Compl. ¶¶70, 74). It is indicated for the treatment of patients with advanced prostate cancer (Compl. ¶67). Its therapeutic function is to achieve and maintain testosterone suppression to medical castration levels (≤ 0.5 ng/mL) without causing the initial testosterone surge associated with GnRH agonist therapies (Compl. ¶¶28, 73). The complaint includes a figure from the FIRMAGON® package insert showing that degarelix achieves rapid testosterone suppression, unlike the GnRH agonist leuprolide which causes an initial spike (Compl. ¶73; Ex. F at § 14, Figure 2). The complaint alleges the proposed product insert for the ANDA product will be substantially similar to the FIRMAGON® insert, thereby recommending a 240 mg starting dose and an 80 mg maintenance dose (Compl. ¶¶68, 74).

IV. Analysis of Infringement Allegations

’359 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating prostate cancer in a subject with a reduced likelihood of causing a testosterone spike or other gonadotrophin releasing hormone (GnRH) agonist side-effect comprising: The ANDA product's proposed label will instruct its use for advanced prostate cancer, and its mechanism as a GnRH antagonist avoids the testosterone spike characteristic of GnRH agonists. The complaint references data showing this effect. ¶¶67, 80-81, 73 (referencing Ex. F at § 14, Figure 2) ’739 Patent, col. 4:45-50
administering an initial dose of 160-320 mg of degarelix to the subject, wherein the initial dose is administered as two subcutaneous injections; and The ANDA product's proposed label will instruct an initial dose of 240 mg, which falls within the claimed range and is to be administered as two separate 120 mg subcutaneous injections. ¶¶68, 70 ’739 Patent, col. 4:50-52
administering a maintenance dose of 60-160 mg of degarelix to the subject once every 20-36 days thereafter, wherein the maintenance dose results in a testosterone suppression below 0.5 ng/mL; The ANDA product's proposed label will instruct a maintenance dose of 80 mg every 28 days, which falls within the claimed ranges, and will include data demonstrating that this regimen maintains testosterone suppression below 0.5 ng/mL (50 ng/dL). ¶¶68, 73 (referencing Ex. F at § 14, Table 3) ’739 Patent, col. 4:52-56
  • Identified Points of Contention:
    • Inducement Questions: Since infringement is based on inducement, a central question will be whether the Defendant's proposed product label sufficiently encourages, recommends, or promotes the performance of every step of the claimed method to physicians. A defense may argue that the label merely provides information, leaving the ultimate infringing acts to the independent medical judgment of the prescriber.

’085 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating prostate cancer in a subject, comprising: selecting a subject with a history of at least one cardiovascular event and prostate cancer; The proposed label will instruct the use of the ANDA product for advanced prostate cancer. The complaint alleges this will induce physicians to treat the general population of such patients, which necessarily includes the sub-population with a history of cardiovascular events. ¶¶67, 89-90 ’398 Patent, col. 7:28-34
administering degarelix to the subject, The proposed label will instruct the administration of the degarelix-containing ANDA product. ¶89 ’398 Patent, col. 8:1-2
wherein administration of degarelix to the subject decreases the frequency of an additional cardiovascular event... as compared to... a gonadotrophin releasing hormone (GnRH) agonist... This is a functional limitation describing the result of the administration. Infringement is premised on the allegation that administering the ANDA product will necessarily achieve this claimed comparative outcome. ¶¶32, 89 ’398 Patent, col. 4:5-14
wherein the at least one cardiovascular event is chosen from myocardial infarction, ischemic heart disease, ischemic stroke, hemorrhagic stroke, and other arterial thrombotic/embolic events. This language defines the scope of the cardiovascular events relevant to the "selecting" and "decreases the frequency" limitations. ¶32 ’398 Patent, col. 1:45-51
  • Identified Points of Contention:
    • Scope Questions: A primary point of contention may be the "selecting" step. A defense could argue that a product label for a broad indication (advanced prostate cancer) does not specifically instruct or encourage physicians to select patients based on their cardiovascular history, and therefore does not induce infringement of this claim limitation.
    • Technical Questions: The infringement allegation relies on a functional outcome—that degarelix "decreases the frequency" of CV events compared to an agonist. A key question will be what evidence is required to prove this functional limitation is met by the use of the accused ANDA product, and whether data from the innovator drug's clinical trials is sufficient to meet the patentee's burden.

V. Key Claim Terms for Construction

  • The Term: "selecting a subject with a history of at least one cardiovascular event" (’085 Patent, Claim 1)

  • Context and Importance: This term is the central active step that defines the specific patient population for the method. Its construction will be critical because Defendant's product will likely be labeled for a broad population of prostate cancer patients, not just this subgroup. Practitioners may focus on this term because the outcome of the inducement analysis could hinge on whether merely prescribing the drug to a patient known to have a CV history constitutes "selecting" under the claim.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent specification discusses identifying a subject "at risk for a cardiovascular disease or disorder" and then administering the drug, which may suggest that "selecting" encompasses the routine diagnostic process of reviewing a patient's medical history before prescribing a therapy (’398 Patent, col. 7:28-34).
    • Evidence for a Narrower Interpretation: A defendant may argue that the term requires an affirmative mental step of choosing degarelix because of the patient's cardiovascular history, an instruction that may be absent from a general-use product label. The patent's focus on comparing outcomes versus agonists could be argued to imply a conscious choice between therapeutic options for this specific patient type (’398 Patent, Abstract).

  • The Term: "reduced likelihood of causing a testosterone spike" (’359 Patent, Claim 1)

  • Context and Importance: This phrase in the preamble sets the purpose and benefit of the claimed method. Its construction is important to frame the context of the invention and may be relevant to infringement if the defendant argues its product does not provide this benefit.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent specification contrasts the claimed method with GnRH agonists, which are known to cause a "testosterone surge" or "flare reaction" (’739 Patent, col. 2:1-24). This context suggests "reduced likelihood" means the substantial or complete avoidance of such a surge, as is characteristic of GnRH antagonists.
    • Evidence for a Narrower Interpretation: The patent includes figures from clinical trials graphically depicting the difference in testosterone response between degarelix and an agonist (’739 Patent, Fig. 3). A defendant could argue the scope of "reduced likelihood" should be limited to a technical effect that is quantitatively similar to the results shown in those specific examples.

VI. Other Allegations

  • Indirect Infringement: The complaint is primarily based on a theory of induced infringement under 35 U.S.C. § 271(b) for all asserted method-of-use patents. It alleges that Defendant's proposed FDA-approved product insert will actively direct, encourage, and aid physicians to perform the steps of the patented methods (Compl. ¶¶ 79-81, 88-90). For the ’938 manufacturing patent, infringement is also alleged under 35 U.S.C. § 271(a) and/or (g) for the importation, use, or sale of a product made by a patented process (Compl. ¶193).
  • Willful Infringement: The complaint does not include a separate count for willful infringement. However, for each patent-in-suit, it alleges that Defendant has knowledge of the patent and knows that use of its ANDA product in accordance with the proposed label will directly infringe (e.g., Compl. ¶¶ 82, 91, 125). This knowledge is premised on at least the pre-suit Paragraph IV notice letter (Compl. ¶61). The complaint also asserts that the case is "exceptional" and seeks attorneys' fees under 35 U.S.C. § 285, which is often associated with allegations of egregious infringement (Compl. ¶¶ 85, 94).

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

  • A core issue will be one of inducement and label scope: For the method-of-use patents, can Plaintiffs demonstrate that Defendant's proposed product label, intended for a broad patient population, will actively encourage or instruct physicians to perform the specific steps of the claimed methods, particularly the "selecting" of patients with specific comorbidities (e.g., a history of cardiovascular events) or the "choosing" of degarelix to avoid specific side effects (e.g., musculoskeletal disorders)?
  • A key evidentiary question will be one of process infringement: For the ’938 manufacturing patent, can Plaintiffs provide sufficient evidence, direct or circumstantial, to establish that Defendant’s process for synthesizing degarelix infringes the claimed method, particularly in light of Plaintiffs' assertion that no other commercially viable, high-purity synthesis methods exist?
  • A central legal question will be one of claim differentiation and obviousness-type double patenting: Given the significant overlap in the inventive concepts across multiple asserted patents (e.g., the ’359/’739 patents on dosing regimens and the ’085/’398 patents on treating patients with CV history), the case may involve significant disputes over whether the claims of later-issued patents are patentably distinct from those of earlier family members.