DCT

3:14-cv-02550

Amarin Pharma Inc v. Apotex Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:14-cv-02550, D.N.J., 04/21/2014
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendants' prior submission to the jurisdiction of the court, plans to sell the accused generic product in New Jersey, existing licenses to sell pharmaceutical products in the state, and receipt of Medicaid reimbursements from drugs sold in New Jersey.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's VASCEPA® pharmaceutical product constitutes an act of infringement of sixteen U.S. patents.
  • Technical Context: The patents relate to methods of treating severe hypertriglyceridemia (abnormally high levels of triglycerides in the blood) and stable pharmaceutical compositions containing highly purified eicosapentaenoic acid (EPA), an omega-3 fatty acid.
  • Key Procedural History: The action was precipitated by Defendant's submission of ANDA No. 205753 to the U.S. Food and Drug Administration (FDA), which sought approval to market a generic version of VASCEPA®. The ANDA filing included a Paragraph IV certification alleging that Plaintiff's patents are invalid and/or will not be infringed by the proposed generic product. Defendant provided Plaintiff with a notice letter dated March 7, 2014, formally advising of the ANDA filing and certification, which is the statutory trigger for this patent infringement action under the Hatch-Waxman Act.

Case Timeline

Date Event
2009-02-10 Earliest Priority Date for '728, '715, '677, '652, '920, '446, '335, '399, '560, '650, '929, '698, '372 Patents
2009-04-29 Earliest Priority Date for '225, '521, '594 Patents
2012-07-26 FDA approves VASCEPA® (NDA No. 202057)
2012-10-23 U.S. Patent No. 8,293,728 Issues
2012-11-27 U.S. Patent No. 8,318,715 Issues
2013-01-22 U.S. Patent No. 8,357,677 Issues
2013-02-05 U.S. Patent No. 8,367,652 Issues
2013-02-19 U.S. Patent No. 8,377,920 Issues
2013-03-19 U.S. Patent No. 8,399,446 Issues
2013-04-09 U.S. Patent No. 8,415,335 Issues
2013-04-23 U.S. Patent No. 8,426,399 Issues
2013-04-30 U.S. Patent No. 8,431,560 Issues
2013-05-14 U.S. Patent No. 8,440,650 Issues
2013-08-06 U.S. Patent No. 8,501,225 Issues
2013-08-27 U.S. Patent No. 8,518,929 Issues
2013-09-03 U.S. Patent No. 8,524,698 Issues
2013-10-01 U.S. Patent No. 8,546,372 Issues
2013-10-08 U.S. Patent No. 8,551,521 Issues
2013-12-31 U.S. Patent No. 8,617,594 Issues
2014-03-07 Apotex sends Paragraph IV Notice Letter to Amarin
2014-04-21 Complaint Filed

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

U.S. Patent No. 8,293,728 - “Methods of Treating Hypertriglyceridemia”

  • Issued: October 23, 2012.

The Invention Explained

  • Problem Addressed: The patent background identifies cardiovascular disease as a leading cause of death in the United States and Europe, noting a need for improved treatments for associated disorders like dyslipidemia (Compl. ¶36; ’728 Patent, col. 1:12-21).
  • The Patented Solution: The invention is a method of blood lipid therapy that involves administering a pharmaceutical composition containing highly purified eicosapentaenoic acid ethyl ester (ethyl-EPA). A key aspect of the solution is the substantial absence of docosahexaenoic acid (DHA), another common omega-3 fatty acid, which the patent suggests may have different physiological effects (’728 Patent, Abstract; col. 2:31-37). The method is claimed to reduce high triglyceride levels in certain patients without the negative side effect of significantly raising LDL-C ("bad cholesterol") levels (’728 Patent, Claim 1).
  • Technical Importance: The claimed method provides a therapeutic option for managing severe hypertriglyceridemia, a significant risk factor for cardiovascular disease, potentially with a more favorable safety profile regarding LDL-C effects compared to other omega-3 fatty acid compositions.

Key Claims at a Glance

  • The complaint asserts one or more claims of the patent (Compl. ¶39). The lead independent claim is Claim 1.
  • Essential elements of Claim 1 include:
    • A method for reducing triglycerides in a subject with a fasting baseline triglyceride level of 500 mg/dl to about 1500 mg/dl who is not on concurrent lipid-altering therapy.
    • The method involves orally administering about 4 g per day of a pharmaceutical composition for 12 weeks.
    • The composition must comprise at least 96% ethyl-EPA by weight of all fatty acids.
    • The composition must contain "substantially no" docosahexaenoic acid (DHA) or its esters.
    • The administration must result in a reduction in triglycerides "without substantially increasing LDL-C."
  • The complaint does not explicitly reserve the right to assert dependent claims, but the allegation of infringing "one or more claims" leaves this possibility open (Compl. ¶39).

U.S. Patent No. 8,318,715 - “Methods of Treating Hypertriglyceridemia”

  • Issued: November 27, 2012.

The Invention Explained

  • Problem Addressed: Similar to the ’728 Patent, this patent addresses the need for improved treatments for cardiovascular-related diseases such as hypertriglyceridemia (’715 Patent, col. 1:12-21).
  • The Patented Solution: The solution is also a method of blood lipid therapy using a highly purified ethyl-EPA composition that is substantially free of DHA (’715 Patent, Abstract; col. 2:25-39). This patent claims a method for reducing not only triglycerides but also apolipoprotein B (Apo B), another marker associated with cardiovascular disease risk (’715 Patent, Claim 1).
  • Technical Importance: This patent expands the claimed therapeutic benefit of the high-purity ethyl-EPA composition to include the reduction of Apo B levels in addition to triglycerides, targeting another key biomarker for cardiovascular risk.

Key Claims at a Glance

  • The complaint asserts one or more claims of the patent (Compl. ¶49). The lead independent claim is Claim 1.
  • Essential elements of Claim 1 include:
    • A method for reducing triglycerides and apolipoprotein B in a subject with a fasting baseline triglyceride level of 500 mg/dl to about 1500 mg/dl who is not on concurrent lipid-altering therapy.
    • The method involves orally administering about 4 g per day of a pharmaceutical composition.
    • The composition must comprise at least 96% ethyl-EPA by weight.
    • The composition must contain "substantially no" docosahexaenoic acid (DHA) or its esters.
  • The complaint's allegation of infringing "one or more claims" leaves open the possibility of asserting dependent claims (Compl. ¶49).

Multi-Patent Capsules

  • U.S. Patent No. 8,357,677, “Methods of Treating Hypertriglyceridemia,” issued January 22, 2013 (Compl. ¶56).

    • Technology Synopsis: This patent is directed to a method of reducing apolipoprotein B (Apo B) levels in a subject with severe hypertriglyceridemia by administering a pharmaceutical composition comprising at least 96% ethyl-EPA by weight and substantially no DHA. This method targets patients who are also on statin therapy (’677 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶59).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, including those on statin therapy, thereby infringing the patent (Compl. ¶59).

  • U.S. Patent No. 8,367,652, “Methods of Treating Hypertriglyceridemia,” issued February 5, 2013 (Compl. ¶66).

    • Technology Synopsis: This patent claims a method of reducing fasting triglycerides in a subject with severe hypertriglyceridemia who is on statin therapy. The method involves administering a composition of at least 96% ethyl-EPA that is substantially free of DHA (’652 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶69).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, including those on statin therapy, infringing the patent (Compl. ¶69).

  • U.S. Patent No. 8,377,920, “Methods of Treating Hypertriglyceridemia,” issued February 19, 2013 (Compl. ¶76).

    • Technology Synopsis: This patent claims a method of reducing non-HDL-C in a subject with severe hypertriglyceridemia and high non-HDL-C levels who is on statin therapy. The method involves administering a composition of at least 96% ethyl-EPA that is substantially free of DHA (’920 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶79).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, infringing the patent (Compl. ¶79).

  • U.S. Patent No. 8,399,446, “Methods of Treating Hypertriglyceridemia,” issued March 19, 2013 (Compl. ¶86).

    • Technology Synopsis: This patent claims a method of reducing VLDL-C in a subject with severe hypertriglyceridemia who is on statin therapy. The method involves administering a composition of at least 96% ethyl-EPA that is substantially free of DHA (’446 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶89).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, infringing the patent (Compl. ¶89).

  • U.S. Patent No. 8,415,335, “Methods of Treating Hypertriglyceridemia,” issued April 9, 2013 (Compl. ¶96).

    • Technology Synopsis: This patent claims a method of reducing total cholesterol in a subject with severe hypertriglyceridemia who is on statin therapy. The method involves administering a composition of at least 96% ethyl-EPA that is substantially free of DHA (’335 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶99).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, infringing the patent (Compl. ¶99).

  • U.S. Patent No. 8,426,399, “Methods of Treating Hypertriglyceridemia,” issued April 23, 2013 (Compl. ¶106).

    • Technology Synopsis: This patent claims a method of reducing remnant-like particle cholesterol (RLP-C) in a subject with severe hypertriglyceridemia who is on statin therapy. The method involves administering a composition of at least 96% ethyl-EPA that is substantially free of DHA (’399 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶109).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, infringing the patent (Compl. ¶109).

  • U.S. Patent No. 8,431,560, “Methods of Treating Hypertriglyceridemia,” issued April 30, 2013 (Compl. ¶116).

    • Technology Synopsis: This patent claims a method of reducing lipoprotein associated phospholipase A2 (Lp-PLA2) in a subject with severe hypertriglyceridemia who is on statin therapy. The method involves administering a composition of at least 96% ethyl-EPA that is substantially free of DHA (’560 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶119).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, infringing the patent (Compl. ¶119).

  • U.S. Patent No. 8,440,650, “Methods of Treating Hypertriglyceridemia,” issued May 14, 2013 (Compl. ¶126).

    • Technology Synopsis: This patent claims a method for reducing triglycerides in a subject with severe hypertriglyceridemia, by administering about 2 g per day of a composition comprising at least 96% ethyl-EPA. This claim is distinct from others by specifying a lower daily dosage (’650 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶129).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, infringing the patent (Compl. ¶129).

  • U.S. Patent No. 8,501,225, “Stable Pharmaceutical Composition and Methods of Using Same,” issued August 6, 2013 (Compl. ¶136).

    • Technology Synopsis: This patent claims a stable pharmaceutical composition comprising ultra-pure EPA encapsulated in a capsule shell that resists oxidation. The claims are directed to the composition itself, focusing on its stability and purity profile over time, rather than a method of treatment (’225 Patent, Abstract).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶139).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product itself, which the complaint alleges will infringe the composition claims (Compl. ¶138).

  • U.S. Patent No. 8,518,929, “Methods of Treating Hypertriglyceridemia,” issued August 27, 2013 (Compl. ¶146).

    • Technology Synopsis: This patent claims a method of increasing HDL-C in a subject with severe hypertriglyceridemia who is on statin therapy. The method involves administering a composition of at least 96% ethyl-EPA that is substantially free of DHA (’929 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶149).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, infringing the patent (Compl. ¶149).

  • U.S. Patent No. 8,524,698, “Methods of Treating Hypertriglyceridemia,” issued September 3, 2013 (Compl. ¶156).

    • Technology Synopsis: This patent claims a method of reducing triglycerides and at least one of Apo B, non-HDL-C, or VLDL-C in a subject on stable statin therapy with baseline triglycerides of 200 to 500 mg/dL. This targets a different patient population than the severe hypertriglyceridemia patents (’698 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶159).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, infringing the patent (Compl. ¶159).

  • U.S. Patent No. 8,546,372, “Methods of Treating Hypertriglyceridemia,” issued October 1, 2013 (Compl. ¶166).

    • Technology Synopsis: This patent claims a method of reducing triglycerides in a subject on stable statin therapy with baseline triglycerides of 200 to 500 mg/dL, without increasing LDL-C by more than 5%. The method involves administering a composition of at least 96% ethyl-EPA that is substantially free of DHA (’372 Patent, Abstract, Claim 1).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶169).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product, which the complaint alleges will be administered to patients to reduce triglyceride levels, infringing the patent (Compl. ¶169).

  • U.S. Patent No. 8,551,521, “Stable Pharmaceutical Composition and Methods of Using Same,” issued October 8, 2013 (Compl. ¶176).

    • Technology Synopsis: This patent, like the ’225 patent, is directed to a stable pharmaceutical composition itself, comprising ethyl eicosapentaenoate in a capsule shell, and specifies a particular dissolution profile and bioavailability (Tmax) (’521 Patent, Abstract).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶179).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product itself, which the complaint alleges will infringe the composition claims (Compl. ¶178).

  • U.S. Patent No. 8,617,594, “Stable Pharmaceutical Composition and Methods of Using Same,” issued December 31, 2013 (Compl. ¶186).

    • Technology Synopsis: This patent is also directed to a stable pharmaceutical composition comprising ethyl eicosapentaenoate. The claims focus on the stability of the composition over time under specified storage conditions, as measured by the amount of EPA remaining and the level of degradation products (’594 Patent, Abstract).
    • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶189).
    • Accused Features: The accused feature is the proposed generic icosapent ethyl product itself, which the complaint alleges will infringe the composition claims (Compl. ¶188).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant’s proposed generic version of VASCEPA®, identified in ANDA No. 205753 (Compl. ¶30). The product is a 1g icosapent ethyl capsule (Compl. ¶30).

Functionality and Market Context

The complaint alleges that the proposed generic product is purportedly bioequivalent to VASCEPA® (Compl. ¶30). Its proposed labeling sets forth the same indication as the approved labeling for VASCEPA®: to be used as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia (Compl. ¶31). The complaint alleges that Apotex’s purpose in filing the ANDA is to engage in the commercial manufacture and sale of this generic version before the expiration of the patents-in-suit (Compl. ¶33).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed, element-by-element mapping of the asserted claims to the accused product, as is common in initial complaints filed under the Hatch-Waxman Act. Instead, it presents a narrative theory of infringement based on the intended use of the proposed generic product as described in its ANDA filing.

'728 Patent Infringement Allegations

Narrative Infringement Theory

The complaint alleges that Apotex's ANDA seeks approval for a product that, if marketed and used as directed, will infringe the method claims of the ’728 Patent (Compl. ¶38). The theory is one of induced infringement: Apotex's proposed label will instruct physicians and patients to administer the generic drug to reduce triglyceride levels in patients with severe hypertriglyceridemia (Compl. ¶39). This instructed use, according to the complaint, will constitute direct infringement of the claimed method, and Apotex, by providing the drug and the instructions, will induce that infringement with knowledge and intent (Compl. ¶39). The filing of the ANDA itself is alleged to be a statutory act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶43).

Identified Points of Contention

  • Scope Questions: A central question will be whether the administration of Apotex's product as instructed by its proposed label will meet all limitations of the asserted claims. For Claim 1, this includes the negative limitation "without substantially increasing LDL-C." The dispute may focus on what clinical evidence from Apotex's ANDA or other sources shows regarding the effect of its product on LDL-C levels.
  • Technical Questions: A factual question for the court will be whether Apotex's proposed generic product, which must be bioequivalent to VASCEPA®, will produce the same clinical outcomes as recited in the claims when administered according to its label. This raises the evidentiary question of what data supports the conclusion that the generic product will not "substantially" increase LDL-C levels in the target patient population.

'715 Patent Infringement Allegations

Narrative Infringement Theory

The infringement theory for the ’715 Patent is analogous to that for the ’728 Patent. The complaint alleges that the use of Apotex's proposed generic product, as directed by its label, will directly infringe the claimed method of reducing both triglycerides and apolipoprotein B (Apo B) (Compl. ¶49). Apotex is alleged to actively induce this infringement (Compl. ¶49). The ANDA filing itself is also alleged to be a statutory act of infringement (Compl. ¶53).

Identified Points of Contention

  • Scope Questions: The analysis may focus on whether the administration of Apotex's product will necessarily result in a reduction of both triglycerides and Apo B, as required by Claim 1.
  • Technical Questions: A key evidentiary question will be whether the clinical data for Apotex's product demonstrates a statistically significant reduction in Apo B levels in the target patient population, in addition to the reduction in triglycerides.

V. Key Claim Terms for Construction

  • The Term: "substantially no docosahexaenoic acid (DHA) or its esters" (from Claim 1 of the ’728 and ’715 Patents).

  • Context and Importance: The asserted patents repeatedly emphasize the high purity of the ethyl-EPA composition and its distinction from other omega-3 products that contain both EPA and DHA. The definition of "substantially no" will be critical to determining the scope of the claims and whether Apotex's product, which may contain trace amounts of DHA, falls within that scope. Practitioners may focus on this term because the precise level of DHA allowable under this term will likely be a central issue in the infringement analysis.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification states, "In one embodiment, the composition contains not more than about 10%, by weight, docosahexaenoic acid or derivative thereof, substantially no docosahexaenoic acid or derivative thereof, or no docosahexaenoic acid or derivative thereof" (’728 Patent, col. 2:31-36). This language could be argued to support a construction where "substantially no" means some non-zero amount, possibly up to a certain percentage that does not materially alter the properties of the composition.
    • Evidence for a Narrower Interpretation: The detailed description of specific embodiments lists compositions where the amount of DHA ethyl ester is "not detected" (’728 Patent, Table 2). This could support an argument that "substantially no" means at or below the limit of detection using standard analytical methods available at the time of the invention.

  • The Term: "without substantially increasing LDL-C" (from Claim 1 of the ’728 Patent).

  • Context and Importance: This is a negative functional limitation that is a cornerstone of the claimed invention's purported benefit. The interpretation of what constitutes a "substantial" increase in LDL-C will be determinative of infringement. Practitioners may focus on this term because it is a term of degree that will require the court to define a clinical threshold for what is "substantial."

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification contrasts the invention with Lovaza®, which is described as increasing LDL-C. The term could be argued to mean any increase that is not statistically significant or is less than the increase caused by comparative prior art treatments (’728 Patent, col. 3:6-8).
    • Evidence for a Narrower Interpretation: The claim language compares the subject's outcome to that of a "second subject." This may suggest that a "substantial" increase is one that is clinically meaningful in a particular patient context, potentially requiring a case-by-case factual analysis rather than a single numerical cutoff (’728 Patent, Claim 1). The patent also describes outcomes such as "no increase in LDL-C levels" and "a reduction in LDL-C levels" (’728 Patent, col. 4:13-15), which could be used to argue that "substantially increasing" requires a notable and statistically significant rise.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for the method patents. The basis for this allegation is that Apotex, if its ANDA is approved, will manufacture and sell its generic product with labeling that instructs physicians and patients to use the product in a manner that directly infringes the asserted method claims (Compl. ¶¶ 39, 49). The complaint alleges this inducement will be done with "intent, knowledge, and encouragement" (Compl. ¶39).
  • Willful Infringement: The complaint does not use the term "willful infringement." However, it alleges that Apotex gave written notice of its certification of invalidity and/or non-infringement, which demonstrates knowledge of the patents-in-suit prior to any commercial launch (Compl. ¶42). The complaint also pleads that the case is "exceptional" and seeks attorneys' fees under 35 U.S.C. § 285, which is often associated with findings of willful infringement or litigation misconduct (Compl. ¶34; Prayer for Relief ¶E).

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

  • A core issue will be one of definitional scope: how will the court construe the term "substantially no docosahexaenoic acid (DHA)"? The case may turn on whether this term is defined as a specific numerical threshold (e.g., less than 1% by weight) or a functional standard (e.g., an amount low enough not to counteract the effects of EPA), and whether Apotex's proposed product meets that definition.
  • A second central issue will be one of clinical effect and proof: what evidence is required to prove or disprove the negative limitation "without substantially increasing LDL-C"? The dispute will likely involve extensive expert testimony and analysis of clinical data to determine if the use of Apotex's generic product results in an LDL-C increase that the court deems "substantial."
  • Given the large number of asserted patents with overlapping subject matter, a significant procedural question will be case management and claim selection: how will the parties and the court narrow the dispute from sixteen patents and hundreds of potential claims to a manageable set for claim construction and trial? The resolution of the core technical and infringement questions for the lead patents will likely be dispositive for many of the related patents in the family.