DCT

1:20-cv-00003

Celgene Corp v. Mylan Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-00003, N.D. W. Va., 09/04/2020
  • Venue Allegations: Plaintiff alleges venue is proper in the Northern District of West Virginia based on Defendant Mylan Pharmaceuticals Inc.'s incorporation and principal place of business in West Virginia, and the systematic and continuous business contacts of all Mylan defendants with the state, including the anticipated marketing and sale of the accused generic products in the district.
  • Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) with the U.S. Food and Drug Administration to market generic versions of Plaintiff's REVLIMID® product constitutes an act of infringement of ten U.S. patents covering the drug's composition, polymorphic forms, and methods of use.
  • Technical Context: The patents relate to the compound lenalidomide, an immunomodulatory drug used in the treatment of multiple myeloma and certain myelodysplastic syndromes, which are types of blood cancer.
  • Key Procedural History: The action arises from Mylan's filing of ANDA No. 213912 and its associated Paragraph IV Certification, which alleges that Celgene's patents are invalid, unenforceable, and/or will not be infringed by Mylan's proposed generic products. The complaint notes that Mylan entities have also filed petitions for Inter Partes Review (IPR) before the Patent Trial and Appeal Board concerning certain patents.

Case Timeline

Date Event
2002-10-15 Priority Date for ’740 Patent
2003-09-04 Priority Date for ’800, ’217, ’569, ’498, ’095, ’120, ’621, ’622 Patents
2007-03-13 ’740 Patent Issued
2008-12-16 ’800 Patent Issued
2010-12-21 ’217 Patent Issued
2011-06-28 ’569 Patent Issued
2013-03-26 ’717 Patent Issued
2013-09-10 ’498 Patent Issued
2014-02-11 ’095 Patent Issued
2015-06-16 ’120 Patent Issued
2015-08-11 ’621 Patent Issued
2015-08-11 ’622 Patent Issued
2019-11-20 Mylan sends Paragraph IV Certification Notice Letter to Celgene
2020-09-04 Complaint Filed

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

U.S. Patent No. 7,189,740 - “Methods of Using 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the Treatment and Management of Myelodysplastic Syndromes,” issued March 13, 2007

The Invention Explained

  • Problem Addressed: The patent describes Myelodysplastic Syndromes (MDS) as a group of hematopoietic stem cell disorders characterized by ineffective blood cell production and a risk of progressing to acute leukemia (ʼ740 Patent, col. 6:21-30). Existing treatments such as bone marrow transplantation were noted to have significant risks and limitations, particularly for the elderly population in which MDS is most common, and therapies with hematopoietic growth factors had proven to have limited efficacy (ʼ740 Patent, col. 7:38-60).
  • The Patented Solution: The invention provides a method for treating, preventing, and managing MDS by administering a therapeutically effective amount of the immunomodulatory compound 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione, also known as lenalidomide (ʼ740 Patent, Abstract). The detailed description presents clinical study data showing that this compound has "remarkable erythropoietic and cytogenetic remitting activity" in MDS patients, including achieving red blood cell transfusion-independence and complete or partial remission of cytogenetic abnormalities (ʼ740 Patent, col. 27:40-59).
  • Technical Importance: This method provided a novel oral therapeutic option for a serious blood cancer that previously had limited effective treatments, particularly for patients who were not candidates for aggressive therapies like transplantation (ʼ740 Patent, col. 7:51-54).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims without specifying them (Compl. ¶59). Independent claim 1 is representative.
  • Claim 1 requires:
    • A method of treating a myelodysplastic syndrome,
    • which comprises administering to a patient in need thereof
    • about 5 to about 50 mg per day of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

U.S. Patent No. 7,465,800 - “Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione,” issued December 16, 2008

The Invention Explained

  • Problem Addressed: The patent explains that chemical compounds can exist in different crystal forms, or polymorphs, which can have different physical and chemical properties such as solubility, stability, and compressibility ('800 Patent, col. 2:20-34). For a pharmaceutical compound, these properties are critical for manufacturing a consistent and effective drug product, and the discovery of new polymorphic forms can yield "numerous formulation, manufacturing and therapeutic benefits" ('800 Patent, col. 2:54-56).
  • The Patented Solution: The invention discloses the discovery and characterization of several distinct polymorphic forms of lenalidomide, designated as Forms A through H ('800 Patent, Abstract; col. 6:11-13). It provides detailed data for identifying these forms, including X-ray powder diffraction (XRPD) patterns, infrared (IR) spectra, and thermal analysis (DSC/TGA) curves, which define their unique solid-state structures ('800 Patent, Figs. 1-46).
  • Technical Importance: Identifying and characterizing specific, stable polymorphic forms of an active pharmaceutical ingredient is a crucial step in developing a safe, effective, and commercially viable oral solid dosage form that can be manufactured consistently.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims without specifying them (Compl. ¶68). Independent claim 1 is representative.
  • Claim 1 requires:
    • Crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate.

U.S. Patent No. 7,855,217 - “Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione,” issued December 21, 2010

  • Technology Synopsis: This patent, similar to the ʼ800 Patent, discloses and claims specific crystalline polymorphic forms of lenalidomide, which is important for ensuring the stability and consistency of the manufactured drug product (Compl. ¶11).
  • Accused Features: Mylan's proposed generic lenalidomide capsules are alleged to contain a solid form of lenalidomide that infringes one or more claims of the patent (Compl. ¶¶20, 77).

U.S. Patent No. 7,968,569 - “Methods For Treatment of Multiple Myeloma Using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione,” issued June 28, 2011

  • Technology Synopsis: This patent claims methods of treating, preventing, or managing multiple myeloma by administering lenalidomide. This represents a different indication from the myelodysplastic syndromes claimed in the '740 patent (Compl. ¶12).
  • Accused Features: The labeling for Mylan's proposed generic product is alleged to instruct or encourage physicians and patients to administer the drug for the treatment of multiple myeloma, thereby infringing the patent (Compl. ¶¶22, 86).

U.S. Patent No. 8,404,717 - “Methods of Treating Myelodysplastic Syndromes Using Lenalidomide,” issued March 26, 2013

  • Technology Synopsis: This patent, similar to the '740 patent, claims methods for treating myelodysplastic syndromes with lenalidomide (Compl. ¶13).
  • Accused Features: The labeling for Mylan's proposed generic product is alleged to instruct or encourage physicians and patients to administer the drug for the treatment of myelodysplastic syndromes (Compl. ¶¶22, 95).

U.S. Patent No. 8,530,498 - “Methods For Treating Multiple Myeloma With 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione,” issued September 10, 2013

  • Technology Synopsis: This patent, similar to the '569 patent, claims methods of treating multiple myeloma by administering lenalidomide (Compl. ¶14).
  • Accused Features: The labeling for Mylan's proposed generic product is alleged to instruct or encourage physicians and patients to use the drug for treating multiple myeloma (Compl. ¶¶22, 104).

U.S. Patent No. 8,648,095 - “Methods For Treating Multiple Myeloma Using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione In Combination With Proteasome Inhibitor,” issued February 11, 2014

  • Technology Synopsis: This patent claims methods for treating multiple myeloma with a combination therapy comprising lenalidomide and a proteasome inhibitor (Compl. ¶15).
  • Accused Features: The labeling for Mylan's proposed generic product is alleged to instruct or encourage physicians and patients to use the drug in the claimed combination therapy (Compl. ¶¶22, 113).

U.S. Patent No. 9,056,120 - “Methods of Treating Myelodysplastic Syndromes with a Combination Therapy Using Lenalidomide and Azacitidine,” issued June 16, 2015

  • Technology Synopsis: This patent claims methods for treating myelodysplastic syndromes with a combination therapy comprising lenalidomide and azacitidine (Compl. ¶16).
  • Accused Features: The labeling for Mylan's proposed generic product is alleged to instruct or encourage physicians and patients to use the drug in the claimed combination therapy (Compl. ¶¶22, 122).

U.S. Patent No. 9,101,621 - “Methods For Treating Multiple Myeloma With 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione After Stem Cell Transplantation,” issued August 11, 2015

  • Technology Synopsis: This patent claims methods for treating multiple myeloma in patients who have undergone stem cell transplantation by administering lenalidomide (Compl. ¶17).
  • Accused Features: The labeling for Mylan's proposed generic product is alleged to instruct or encourage physicians and patients to administer the drug in the claimed therapeutic setting (Compl. ¶¶22, 131).

U.S. Patent No. 9,101,622 - “Methods For Treating Newly Diagnosed Multiple Myeloma 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione In Combination With Dexamethasone,” issued August 11, 2015

  • Technology Synopsis: This patent claims methods for treating newly diagnosed multiple myeloma with a combination therapy comprising lenalidomide and dexamethasone (Compl. ¶18).
  • Accused Features: The labeling for Mylan's proposed generic product is alleged to instruct or encourage physicians and patients to use the drug in the claimed combination therapy (Compl. ¶¶22, 140).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are "Mylan's Proposed Products," identified as generic lenalidomide capsules in 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg dosages (Compl. ¶53). The act of infringement is the submission of Abbreviated New Drug Application (ANDA) No. 213912 to the FDA, seeking approval to market these products before the expiration of the patents-in-suit (Compl. ¶¶1, 53, 59).

Functionality and Market Context

  • The proposed products are generic versions of Celgene's REVLIMID®, an oral medication used for treating certain types of cancer (Compl. ¶1). The complaint alleges that the filing of the ANDA is an artificial act of infringement under 35 U.S.C. § 271(e)(2)(A), which creates a justiciable controversy between the parties (Compl. ¶¶59, 60). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed claim chart or specify which claims of each patent are asserted. The infringement allegations are based on the statutory act of filing an ANDA under 35 U.S.C. § 271(e)(2)(A). The following charts summarize the infringement theories that may be inferred from the complaint for the two lead patents.

7,189,740 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a myelodysplastic syndrome, Mylan's Proposed Products are intended for the treatment of myelodysplastic syndromes, and the proposed product labeling allegedly instructs and encourages this use. ¶22 col. 6:21-30
which comprises administering to a patient in need thereof The proposed product labeling instructs physicians and patients on the administration of the generic lenalidomide capsules. ¶22 col. 6:1-6
about 5 to about 50 mg per day of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione... Mylan's Proposed Products are lenalidomide capsules in dosages including 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg, which fall within the claimed dosage range. ¶53 col. 17:46-54

7,465,800 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione Mylan's Proposed Products are alleged to be or contain solid forms of lenalidomide. ¶20 col. 6:14-22
hemihydrate. The solid form of lenalidomide in Mylan's Proposed Products is alleged to be the claimed crystalline hemihydrate form. ¶20 col. 7:1-6; Fig. 9

Identified Points of Contention

  • Scope Questions: For the method patents (e.g., '740 Patent), a central question may be whether the language of Mylan's proposed product labeling will be found to instruct or encourage each of the specific steps recited in the asserted claims, thereby meeting the standard for induced infringement.
  • Technical Questions: For the polymorph patents (e.g., '800 Patent), the dispute will likely focus on a factual question of chemical structure: what is the actual crystalline form of lenalidomide in Mylan's proposed generic product, and does it meet the limitations defining the claimed "hemihydrate" polymorph as characterized in the patent?

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for a full analysis of claim construction disputes. However, based on the subject matter of the patents, practitioners may focus on the following terms:

Term: "treating a myelodysplastic syndrome" ('740 Patent, Claim 1)

  • Context and Importance: The definition of this term is critical for determining the scope of the method of use claims. The dispute will likely center on whether the specific indications for use described in Mylan's proposed product label fall within the construction of this term as understood from the patent's specification and prosecution history.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification describes MDS broadly as a "diverse group of hematopoietic stem cell disorders" characterized by "ineffective blood cell production" ('740 Patent, col. 6:21-26), potentially supporting a construction that covers a wide range of conditions.
    • Evidence for a Narrower Interpretation: The detailed description focuses on specific patient populations and clinical outcomes, such as those with transfusion-dependence or specific cytogenetic abnormalities like del(5q) ('740 Patent, col. 27:35-42; col. 28:33-44), which might be argued to limit the scope of "treating" to these specific contexts.

Term: "hemihydrate" ('800 Patent, Claim 1)

  • Context and Importance: This term defines the specific crystalline structure of the claimed composition of matter. The infringement analysis for the '800 patent will turn on whether Mylan's product contains this exact polymorph. The construction will determine what analytical data (e.g., specific XRPD peaks, TGA weight loss percentage, DSC endotherms) is required to prove the presence of the claimed "hemihydrate."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The term itself has a plain chemical meaning (a crystal containing one molecule of water for every two molecules of the compound). A party might argue for this plain meaning, allowing for some variation in analytical results.
    • Evidence for a Narrower Interpretation: The patent provides extensive and specific characterization data for "Form B," which is identified as the hemihydrate. This includes a thermogravimetric analysis showing a weight loss of "about 3.1% volatiles" corresponding to "approximately 0.46 moles of water" ('800 Patent, col. 7:1-4), and a specific XRPD pattern with key peaks ('800 Patent, Fig. 6; col. 6:55-62). A party could argue that the term "hemihydrate" is strictly defined by this specific data set.

VI. Other Allegations

  • Indirect Infringement: For each asserted patent, the complaint alleges both induced and contributory infringement. The inducement allegations are based on the assertion that Mylan's product labeling will instruct and encourage physicians and patients to perform the infringing methods of use (Compl. ¶¶ 22, 62, 71). The contributory infringement allegations are based on the assertion that Mylan's products are especially adapted for an infringing use and have no substantial non-infringing use (Compl. ¶¶ 63, 72).
  • Willful Infringement: The complaint does not use the term "willful infringement," but alleges that this is an "exceptional case" and seeks attorneys' fees under 35 U.S.C. § 285 for each count (e.g., Compl. ¶ 66). The factual basis for this appears to be Mylan's alleged knowledge of the patents-in-suit, evidenced by its submission of the Paragraph IV Certification and the subsequent Notice Letter to Celgene (Compl. ¶¶ 55, 57).

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

  • A central issue will be one of structural identity: for the composition of matter patents ('800, '217), what is the precise polymorphic form of the lenalidomide active ingredient in Mylan's proposed generic product, and does the analytical evidence show that it is the same as one of the claimed crystalline forms?
  • A key question for the method of use patents ('740, '569, etc.) will be one of induced infringement: will the language in Mylan's proposed label be found by the court to actively encourage or instruct medical professionals and patients to administer the generic drug in a manner that practices the specific steps claimed in Celgene's patents?
  • A broader question underlying the entire litigation will be the validity of the asserted patent claims, an issue raised by Mylan in its Paragraph IV certification and likely being litigated in parallel Inter Partes Review proceedings.