DCT

2:18-cv-10775

Celgene Corp v. Synthon Pharmeceuticals Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:18-cv-10775, D.N.J., 11/20/2018
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey based on Defendants' business operations, systematic contacts within the state, and the foreseeable harm caused in New Jersey by the filing of an Abbreviated New Drug Application (ANDA) seeking to market a generic drug product there.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an ANDA to market generic versions of Plaintiff's POMALYST® (pomalidomide) capsules infringes five U.S. patents covering the drug's formulation and methods of use for treating multiple myeloma.
  • Technical Context: The dispute concerns immunomodulatory drugs known as IMiDs®, specifically pomalidomide, which are used to treat multiple myeloma, a cancer of plasma cells.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants' submission of ANDA No. 210232 to the U.S. Food and Drug Administration (FDA). In connection with the ANDA, Defendants filed a "Paragraph IV Certification" alleging that Plaintiff's patents are invalid, unenforceable, or will not be infringed by the proposed generic product. Defendants provided notice of this certification to Plaintiff in letters sent in May and October 2018.

Case Timeline

Date Event
2002-05-17 Earliest Priority Date for ’262, ’939, and ’428 Patents
2009-05-19 Earliest Priority Date for ’427 and ’467 Patents
2012-06-12 U.S. Patent No. 8,198,262 Issues
2014-03-18 U.S. Patent No. 8,673,939 Issues
2014-05-27 U.S. Patent No. 8,735,428 Issues
2014-09-09 U.S. Patent No. 8,828,427 Issues
2018-05-04 Defendants' Paragraph IV Notice Letter Sent to Plaintiff (for '262, '939, '428, '427 Patents)
2018-06-12 U.S. Patent No. 9,993,467 Issues
2018-10-05 Defendants' Paragraph IV Notice Letter Sent to Plaintiff (for '467 Patent)
2018-11-20 Complaint Filed

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

U.S. Patent No. 8,198,262 - "Methods for treating multiple myeloma using 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione"

  • Patent Identification: U.S. Patent No. 8,198,262, "Methods for treating multiple myeloma using 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione," issued June 12, 2012. (Compl. ¶7).

The Invention Explained

  • Problem Addressed: The patent's background describes the significant drawbacks of conventional cancer therapies, including surgery, chemotherapy, and radiation. These drawbacks include severe side effects, toxicity, and the development of drug resistance in many tumor cells, creating a need for safer and more effective treatment methods. (’262 Patent, col. 2:19-64).
  • The Patented Solution: The invention provides methods for treating, preventing, and managing cancer, specifically multiple myeloma, by administering an immunomodulatory compound, 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione (pomalidomide). The patent discloses specific dosing regimens, including cyclical administration of pomalidomide in combination with other therapeutic agents like dexamethasone, to achieve a therapeutic effect. (’262 Patent, Abstract; col. 3:40-5:14).
  • Technical Importance: This therapeutic approach provided a novel mechanism of action for treating cancers like multiple myeloma by modulating the body's immune response and inhibiting cytokine production (e.g., TNF-α), offering an alternative to traditional cytotoxic chemotherapy. (’262 Patent, col. 3:21-36).

Key Claims at a Glance

  • The complaint asserts one or more claims of the ’262 patent without specifying which ones. (Compl. ¶¶50, 52). Claim 1 is the first independent claim.
  • Independent Claim 1:
    • A method of treating multiple myeloma,
    • which comprises administering to a patient having multiple myeloma:
    • (a) from about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide]... for 21 consecutive days followed by seven consecutive days of rest from administration of said compound in a 28 day cycle, and
    • (b) 40 mg of dexamethasone.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 8,673,939 - "Methods for treating multiple myeloma with 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione"

  • Patent Identification: U.S. Patent No. 8,673,939, "Methods for treating multiple myeloma with 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione," issued March 18, 2014. (Compl. ¶8).

The Invention Explained

  • Problem Addressed: As with the related ’262 Patent, this patent addresses the need for effective cancer treatments, particularly for patients whose disease is refractory or resistant to conventional chemotherapy. (’939 Patent, col. 2:19-3:14).
  • The Patented Solution: The invention provides a method of treating multiple myeloma in patients who have already undergone prior therapies. The method involves administering pomalidomide, an immunomodulatory compound, in specific cyclical dosing regimens, often in combination with agents like dexamethasone, to manage the disease in this pre-treated patient population. (’939 Patent, Abstract; col. 3:50-4:6).
  • Technical Importance: This method provided a specific therapeutic pathway for patients with relapsed or refractory multiple myeloma, a patient population with limited treatment options after failing initial therapies. (’939 Patent, col. 16:20-30).

Key Claims at a Glance

  • The complaint asserts one or more claims of the ’939 patent without specifying which ones. (Compl. ¶¶59, 61). Claim 1 is the first independent claim.
  • Independent Claim 1:
    • A method of treating multiple myeloma,
    • which comprises administering to a patient having multiple myeloma, and which patient has received previous therapy for multiple myeloma,
    • from about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide]...
    • wherein the compound is administered in one or more cycles, each of which comprises administering the compound for a period of time followed by a period of rest.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 8,735,428 - "Methods for treating multiple myeloma with 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione"

  • Patent Identification: U.S. Patent No. 8,735,428, "Methods for treating multiple myeloma with 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione," issued May 27, 2014. (Compl. ¶9).
  • Technology Synopsis: This patent, related to the ’262 and ’939 patents, discloses methods of treating multiple myeloma in patients who have received previous therapy and have demonstrated disease progression. The solution involves administering pomalidomide in specific cyclical regimens. (’428 Patent, Abstract; col. 39:2-10).
  • Asserted Claims: The complaint asserts one or more claims without specification. Independent claims include 1 and 22. (Compl. ¶¶68, 70).
  • Accused Features: The accused feature is the proposed use of Defendants' generic pomalidomide capsules for the treatment of multiple myeloma in a manner that will allegedly be instructed by the product's labeling. (Compl. ¶¶15, 68).

U.S. Patent No. 8,828,427 - "Formulations of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione"

  • Patent Identification: U.S. Patent No. 8,828,427, "Formulations of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione," issued September 9, 2014. (Compl. ¶10).
  • Technology Synopsis: This patent addresses the technical problem of creating stable and manufacturable solid dosage forms of pomalidomide. The patented solution is a specific pharmaceutical composition, typically for a capsule, comprising pomalidomide, pregelatinized starch, mannitol, and sodium stearyl fumarate in particular amounts and ratios. (’427 Patent, Abstract; col. 1:12-38).
  • Asserted Claims: The complaint asserts one or more claims without specification. Independent claims include 1-12. (Compl. ¶¶77, 79).
  • Accused Features: The accused feature is the formulation of Defendants' proposed generic pomalidomide capsules as described in their ANDA, which is alleged to contain the same components as the claimed invention. (Compl. ¶¶44, 77).

U.S. Patent No. 9,993,467 - "Formulations of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione"

  • Patent Identification: U.S. Patent No. 9,993,467, "Formulations of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione," issued June 12, 2018. (Compl. ¶11).
  • Technology Synopsis: This patent, related to the ’427 Patent, also discloses stable pharmaceutical formulations of pomalidomide. It claims specific compositions for oral dosage forms, such as capsules, containing pomalidomide and a set of excipients including starch and mannitol, designed to ensure stability and proper delivery of the active ingredient. (’467 Patent, Abstract; col. 1:12-38).
  • Asserted Claims: The complaint asserts one or more claims without specification. Independent claims include 1-8. (Compl. ¶¶86, 88).
  • Accused Features: The accused feature is the physical composition of Defendants' proposed generic pomalidomide capsules, which is alleged to infringe the claimed formulations. (Compl. ¶¶44, 86).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants' proposed generic pomalidomide capsules in 1 mg, 2 mg, 3 mg, and 4 mg dosage strengths, referred to as "Synthon's Proposed Products." (Compl. ¶44).

Functionality and Market Context

The proposed products are generic versions of Celgene's POMALYST® drug product, an FDA-approved medication for the treatment of multiple myeloma. (Compl. ¶12). The action is based on Defendants' filing of ANDA No. 210232 with the FDA, which constitutes a statutory act of infringement under 35 U.S.C. § 271(e)(2). (Compl. ¶¶1, 50). The complaint alleges that the labeling for the proposed generic product will instruct and encourage physicians and patients to administer it according to the methods claimed in the patents-in-suit. (Compl. ¶15). The proposed generic products seek to enter the U.S. market before the expiration of Plaintiff's patents listed in the FDA's Orange Book. (Compl. ¶¶14, 44).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’262 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating multiple myeloma, which comprises administering to a patient having multiple myeloma: The proposed product is a generic version of POMALYST®, an FDA-approved medication for treating multiple myeloma, and its label will allegedly instruct for this use. ¶¶12, 15, 44 col. 33:1-38:46
(a) from about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide] The ANDA seeks approval for 1 mg, 2 mg, 3 mg, and 4 mg capsules, which are within the claimed dosage range. ¶44 col. 37:50-53
for 21 consecutive days followed by seven consecutive days of rest from administration of said compound in a 28 day cycle, The product's label will allegedly instruct physicians and patients to administer the drug according to this specific 21/7 day cycle, mirroring the approved regimen for POMALYST®. ¶15 col. 37:53-56
and (b) 40 mg of dexamethasone. The product's label will allegedly instruct for co-administration with dexamethasone, consistent with the standard of care and the POMALYST® label. ¶15 col. 37:57-58

’939 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating multiple myeloma... in a patient... which patient has received previous therapy for multiple myeloma, The POMALYST® label, which the proposed generic label will allegedly mirror, is for patients with relapsed and refractory multiple myeloma, who by definition have received prior therapies. ¶¶12, 15 col. 39:2-5
from about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide] The ANDA seeks approval for 1 mg, 2 mg, 3 mg, and 4 mg capsules, dosages which fall within the claimed range. ¶44 col. 39:5-6
wherein the compound is administered in one or more cycles, each of which comprises administering the compound for a period of time followed by a period of rest. The proposed product label will allegedly instruct for cyclical administration (e.g., 21 days on, 7 days off), consistent with the approved use of POMALYST®. ¶15 col. 39:12-16

Identified Points of Contention

  • Scope Questions: For the method-of-use patents ('262, '939, '428), a central question will be whether the language of the Defendants' proposed product label will direct or encourage administration in a manner that meets every limitation of the asserted claims. The complaint does not contain the proposed label, so this remains an open evidentiary question.
  • Technical Questions: For the formulation patents ('427, '467), the infringement analysis will turn on a direct comparison between the claimed compositions and the specific formulation disclosed in Defendants' confidential ANDA filing. The complaint does not provide sufficient detail for analysis of the precise excipient ratios and weights in the accused products.

V. Key Claim Terms for Construction

  • The Term: "treating multiple myeloma" (from '262 Patent, Claim 1; '939 Patent, Claim 1)

  • Context and Importance: The definition of "treating" is fundamental to the scope of the method claims. The parties may dispute whether the actions encouraged by the generic label constitute "treating" as understood in the patent, which could be critical for the induced infringement analysis.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent specification states that the invention relates to "methods of treating, preventing and/or managing specific cancers," suggesting the term encompasses a wide range of clinical activities beyond just curing the disease. (’262 Patent, col. 1:15-18).
    • Evidence for a Narrower Interpretation: The detailed description provides specific clinical trial results and outcomes, such as achieving a certain level of M-protein reduction or disease stabilization. (’262 Patent, col. 35:5-36:15). A defendant might argue that "treating" should be limited to achieving these specific, demonstrated clinical endpoints.

  • The Term: "about 1 mg to about 5 mg per day" (from '262 Patent, Claim 1; '939 Patent, Claim 1)

  • Context and Importance: The scope of "about" is critical because infringement hinges on whether the dosages in the accused product (1, 2, 3, and 4 mg) fall within the claimed range. Practitioners may focus on this term because it defines the numerical boundary of the invention.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification discloses a very wide range of possible dosages, from "about 0.10 to about 150 mg/day," which could support an interpretation that the numbers are not meant to be rigid and that "about" allows for reasonable variance. (’262 Patent, col. 18:11-12).
    • Evidence for a Narrower Interpretation: The claim language itself recites a much narrower range ("about 1 mg to about 5 mg") than the broad disclosure. This suggests the inventors considered this specific range to be particularly important to the invention, which may support a narrower construction of "about." (’262 Patent, col. 37:50-53).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for all five patents-in-suit. The allegations are based on the assertion that Defendants' proposed product labeling will instruct and encourage physicians, pharmacists, and patients to use the generic pomalidomide capsules in a manner that directly infringes the asserted claims. (Compl. ¶¶15, 53, 62, 71, 80, 89). Knowledge is alleged based on Defendants' filing of the ANDA and the accompanying Paragraph IV certification, which demonstrates awareness of the patents-in-suit. (Compl. ¶¶46-48).
  • Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, for each count, it alleges the case is "an exceptional one" and requests an award of reasonable attorneys' fees under 35 U.S.C. § 285. (Compl. ¶¶57, 66, 75, 84, 93).

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

  • A central issue for the method-of-use claims will be one of induced infringement: will the final, FDA-approved label for Defendants' generic product contain instructions that direct or encourage physicians to perform every step of the asserted claims, particularly regarding the specified patient population (e.g., previously treated), dosing schedule, and combination with dexamethasone?
  • A key factual question for the formulation claims will be one of compositional identity: does the precise formulation of excipients (e.g., mannitol, starch) disclosed in Defendants' confidential ANDA filing fall within the scope of the asserted composition claims, an issue that will turn on discovery and expert analysis of pharmaceutical formulation?
  • The dispositive issue, underlying the entire case though not detailed in the complaint, will be patent validity: can Defendants prove by clear and convincing evidence that the claimed methods and formulations were anticipated or rendered obvious by the state of the art prior to the patents' priority dates, as asserted in their Paragraph IV certification?