DCT

2:13-cv-04022

Horizon Pharma Inc v. Mylan Pharmaceuticals

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:13-cv-04022, D.N.J., 06/28/2013
  • Venue Allegations: Plaintiffs allege venue is proper in the District of New Jersey based on Defendants’ continuous and systematic contacts with the district, including the sale of pharmaceutical products and deriving substantial revenues from those sales.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug VIMOVO® constitutes infringement of seven patents related to the active ingredient esomeprazole, specific formulations thereof, and methods for its coordinated delivery with the non-steroidal anti-inflammatory drug (NSAID) naproxen.
  • Technical Context: The technology involves proton pump inhibitors (PPIs), which reduce gastric acid, and their formulation into stable, optically pure forms, as well as combination drug products designed to reduce the gastrointestinal side effects of NSAIDs.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 204920 and service of a "Paragraph IV" notice letter dated May 16, 2013, which asserted that the patents-in-suit are invalid or will not be infringed by the proposed generic product. The complaint also notes the existence of several other pending lawsuits involving Plaintiffs and other generic manufacturers concerning patents on esomeprazole magnesium formulations, and requests the case be assigned to the same judge for judicial economy.

Case Timeline

Date Event
1993-05-28 Earliest Priority Date ('504, '872 Patents)
1994-07-15 Earliest Priority Date ('789 Patent)
1997-05-30 Earliest Priority Date ('085, '070, '466 Patents)
1998-02-03 '504 Patent Issued
1999-09-07 '789 Patent Issued
2001-06-01 Earliest Priority Date ('907 Patent)
2002-04-09 '085 Patent Issued
2005-04-05 '872 Patent Issued
2005-08-09 '907 Patent Issued
2008-08-12 '070 Patent Issued
2010-06-29 '466 Patent Issued
2013-05-16 Defendants Serve Paragraph IV Notice Letter
2013-06-28 Complaint Filed

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

U.S. Patent No. 5,714,504 - "Compositions," Issued February 3, 1998

The Invention Explained

  • Problem Addressed: The patent's background describes the difficulty in separating the two optical isomers (enantiomers) of the anti-ulcer drug omeprazole on a preparative scale. It notes that prior methods yielded unstable, non-crystalline syrups and involved a neutralization process that was disadvantageous for large-scale production due to the risk of degrading the acid-sensitive compound ('504 Patent, col. 1:26-44).
  • The Patented Solution: The invention provides novel, optically pure alkaline salts (e.g., sodium, magnesium) of the single enantiomers of omeprazole. These salts can be obtained as stable, crystalline products, which overcomes the stability and handling problems of the prior art's non-crystalline forms and allows for purification through crystallization ('504 Patent, Abstract; col. 2:48-55; col. 3:41-45).
  • Technical Importance: This innovation enabled the development of a single-enantiomer version of omeprazole (esomeprazole) with improved pharmacokinetic properties and a more consistent therapeutic profile compared to the racemic original drug ('504 Patent, col. 2:48-52).

Key Claims at a Glance

The complaint does not specify which claims are asserted, alleging infringement of "the '504 patent claims" generally (Compl. ¶36). Independent claim 1 is representative:

  • A pharmaceutical formulation for oral administration comprising:
  • a pure solid state alkaline salt of the (-)-enantiomer of 5-methoxy-2[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole, and
  • a pharmaceutically acceptable carrier.

U.S. Patent No. 6,369,085 - "Form of S-Omeprazole," Issued April 9, 2002

The Invention Explained

  • Problem Addressed: While the '504 patent disclosed alkaline salts of S-omeprazole (the (-)-enantiomer), there was a need to identify and characterize a specific, stable, and reproducible crystalline form of the magnesium salt suitable for large-scale pharmaceutical manufacturing ('085 Patent, col. 1:11-14, 21-29).
  • The Patented Solution: The invention is directed to a novel, substantially pure crystalline form of the magnesium salt of S-omeprazole trihydrate. This specific form is characterized by a unique X-ray powder diffraction (XRPD) pattern, shown in the patent's FIG. 1. The patent describes this form as more stable and easier to handle and characterize than previously known forms ('085 Patent, Abstract; col. 2:21-29).
  • Technical Importance: The identification of a specific, stable crystalline polymorph is critical in pharmaceutical development for ensuring batch-to-batch consistency, predictable dissolution rates, and long-term product stability.

Key Claims at a Glance

The complaint does not specify which claims are asserted (Compl. ¶50). Independent claim 1 is representative:

  • The magnesium salt of S-omeprazole trihydrate, wherein the compound is characterized by the following major peaks in its X-ray diffractogram:
  • [A list of specific d-values and relative intensities corresponding to the XRPD pattern].

U.S. Patent No. 6,875,872 - "Compounds," Issued April 5, 2005

Technology Synopsis

This patent, related to the '504 patent, claims optically pure alkaline salts of the enantiomers of omeprazole, including the magnesium salt of the (-)-enantiomer (esomeprazole) ('872 Patent, Abstract). The invention provides for stable, crystalline forms of the single-enantiomer drug.

Asserted Claims

The complaint asserts infringement of "the '872 patent claims" (Compl. ¶65).

Accused Features

The complaint alleges that the esomeprazole magnesium salt contained in Defendants' ANDA Products infringes the patent (Compl. ¶62).

U.S. Patent No. 7,411,070 - "Form of S-Omeprazole," Issued August 12, 2008

Technology Synopsis

This patent, related to the '085 patent, is directed to a specific crystalline form of the magnesium salt of S-omeprazole trihydrate, characterized by its X-ray powder diffraction pattern. It also covers processes for its preparation and pharmaceutical compositions containing it ('070 Patent, Abstract).

Asserted Claims

The complaint asserts infringement of "the '070 patent claims" (Compl. ¶79).

Accused Features

The complaint alleges that the compound contained in Defendants' ANDA Products infringes the patent (Compl. ¶77).

U.S. Patent No. 7,745,466 - "Form of S-Omeprazole," Issued June 29, 2010

Technology Synopsis

This patent claims pharmaceutical compositions containing a magnesium salt of S-omeprazole trihydrate as a first active ingredient and a second active ingredient, along with methods of treatment (Compl. ¶81).

Asserted Claims

The complaint asserts infringement of "the '466 patent claims" (Compl. ¶94).

Accused Features

The complaint alleges that the ANDA Products, which contain both esomeprazole magnesium and naproxen, infringe the patent's composition claims (Compl. ¶91).

U.S. Patent No. 6,926,907 - "Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs," Issued August 9, 2005

Technology Synopsis

This patent addresses the problem of gastrointestinal damage caused by NSAIDs. The invention is a pharmaceutical dosage form that provides for the coordinated release of an acid inhibitor (like a PPI) and an NSAID, such that the NSAID is not released until the gastric pH has been raised to a safer level ('907 Patent, Abstract).

Asserted Claims

The complaint does not specify claims but alleges infringement of "the '907 patent claims" (Compl. ¶111).

Accused Features

The complaint alleges that the ANDA Products, which are delayed-release tablets containing both an acid inhibitor (esomeprazole) and an NSAID (naproxen), infringe the patent (Compl. ¶96, ¶107).

U.S. Patent No. 5,948,789 - "Process For Synthesis Of Substituted Sulphoxides," Issued September 7, 1999

Technology Synopsis

This patent describes an enantioselective process for synthesizing sulfoxide compounds, such as omeprazole and its enantiomers. The process involves an asymmetric oxidation of a pro-chiral sulfide using a specific chiral titanium complex as a catalyst ('789 Patent, Abstract).

Asserted Claims

The complaint asserts infringement of "the claims of the '789 patent" (Compl. ¶118, ¶119).

Accused Features

The complaint alleges on information and belief that the esomeprazole magnesium in Defendants' proposed products was produced by a method patented in the '789 patent, thereby infringing under 35 U.S.C. § 271(g) (Compl. ¶116).

III. The Accused Instrumentality

Product Identification

Defendants' proposed naproxen/esomeprazole magnesium delayed-release tablets in 375 mg/20 mg and 500 mg/20 mg dosages, referred to as the "ANDA Products" (Compl. ¶14).

Functionality and Market Context

The ANDA Products are identified as generic versions of the branded VIMOVO® product (Compl. ¶14). They are combination drugs containing naproxen, an NSAID for treating pain and inflammation, and esomeprazole magnesium, a PPI used to reduce the risk of gastric ulcers associated with NSAID use (Compl. ¶14, ¶33). The filing of ANDA No. 204920 seeks FDA approval to manufacture and sell these products in the United States prior to the expiration of Plaintiffs' patents (Compl. ¶14).

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed, element-by-element analysis of infringement for any specific patent claim. Instead, it makes general allegations that the proposed ANDA Products, by virtue of containing esomeprazole magnesium and naproxen in a delayed-release formulation, will infringe the asserted patents (Compl. ¶¶ 36, 50). The act of infringement cited is the filing of the ANDA itself under 35 U.S.C. § 271(e)(2) (Compl. ¶32). As such, a claim chart summary cannot be constructed from the complaint's allegations.

  • Narrative Infringement Theory:

    • For '504, '872, '085, '070, and '466 Patents: The core theory is one of direct infringement. The complaint alleges that Defendants' proposed products contain esomeprazole magnesium, including a specific crystalline trihydrate form, which is the subject matter of these patents' claims. The combination of esomeprazole and naproxen in the ANDA product is alleged to infringe the composition claims of the '466 patent (Compl. ¶91).
    • For '907 Patent: The theory is that the administration of Defendants' delayed-release combination tablet for treating pain will directly infringe the method claims directed to the coordinated delivery of an acid inhibitor and an NSAID (Compl. ¶96, ¶106).
    • For '789 Patent: The theory is that the esomeprazole magnesium active ingredient in the ANDA products is or will be manufactured using the patented process, and therefore the importation, sale, or use of the final drug product constitutes infringement under 35 U.S.C. § 271(g) (Compl. ¶116-119).

  • Identified Points of Contention:

    • Technical Questions: A primary technical question for the '085, '070, and '466 patents will be whether the specific crystalline form of esomeprazole magnesium trihydrate in Defendants' ANDA Products exhibits the X-ray powder diffraction pattern claimed in those patents. The complaint provides no evidentiary basis for this, making it a central issue for discovery. For the '789 process patent, the key factual question is what manufacturing process is actually used by Defendants or their supplier to synthesize the esomeprazole.
    • Scope Questions: For the '907 patent, a potential dispute may arise over the meaning of "coordinated delivery." The analysis will question whether the specific release profile of Defendants' product (e.g., the timing and pH-trigger for the release of naproxen relative to esomeprazole) falls within the scope of the claims as construed by the court.

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

The Term: "optically pure" ('504 Patent)

Context and Importance

This term is central to the scope of the '504 patent's claims to single-enantiomer salts. The degree of enantiomeric excess required to meet this limitation will be a critical issue. Practitioners may focus on this term because a defendant could argue that its product, if containing more than a de minimis amount of the R-enantiomer, is not "optically pure."

Intrinsic Evidence for Interpretation

  • Evidence for a Narrower Interpretation: The specification explicitly states that through crystallization, the salts can be obtained in "very high optical purity, namely ≥99.8% enantiomeric excess (e.e.)" ('504 Patent, col. 3:45-48). This language may support a construction requiring a very high, numerically-defined level of purity.
  • Evidence for a Broader Interpretation: The patent also uses less restrictive phrases like "single enantiomers" and describes the invention as providing salts of "optically pure omeprazole" generally ('504 Patent, col. 2:42-44). This could support a construction that is less stringent than 99.8% e.e. and means essentially free of the other enantiomer.

The Term: A compound characterized by the X-ray diffractogram "substantially in accordance with FIG. 1" ('085 Patent, Claim 1)

Context and Importance

Claims defined by instrumental data like an XRPD pattern often lead to disputes over how closely an accused product's data must match the patent's reference data. The term "substantially" introduces flexibility, the scope of which will be contested. The case may turn on whether minor shifts in peak positions or variations in relative intensities, potentially due to different testing conditions, fall within the claim.

Intrinsic Evidence for Interpretation

  • Evidence for a Narrower Interpretation: The patent provides a table with specific d-values and relative intensity categories (e.g., "vs", "s", "m") corresponding to FIG. 1 ('085 Patent, Table 1, col. 5). A party could argue that "substantially" means encompassing only minor, expected experimental variations from this specific data set.
  • Evidence for a Broader Interpretation: The patent does not explicitly define "substantially" or provide a range of acceptable variation for the XRPD peaks. This lack of an explicit definition may support a broader interpretation that captures any crystalline form that is recognizably the same polymorph, even with some differences in the measured pattern.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will induce infringement by encouraging, aiding, and abetting the administration of the ANDA Products to patients for the treatment of gastrointestinal inflammatory diseases and other conditions, with knowledge that such use is in contravention of Plaintiffs' patent rights (Compl. ¶33, ¶47, ¶61). This is premised on the proposed product label, which will instruct physicians and patients to use the drug in an infringing manner.
  • Willful Infringement: The prayer for relief seeks a judgment that infringement is willful (Prayer for Relief (e)). This allegation is predicated on Defendants' pre-suit knowledge of the patents-in-suit, as evidenced by their filing of a Paragraph IV certification and serving the May 16, 2013 Notice Letter, which explicitly addresses the patents (Compl. ¶15, ¶18).

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

  • A core issue will be one of evidentiary proof: Can Plaintiffs, through discovery, obtain evidence demonstrating that Defendants' proposed generic product meets the specific technical limitations of the asserted patents? This includes proving that the esomeprazole magnesium has the specific crystalline structure claimed in the '085 patent family and, for the '789 patent, that it was manufactured using the claimed process.
  • A second key question will be one of validity: Defendants have asserted that the patents-in-suit are invalid. The case will likely involve significant disputes over whether the claimed inventions—ranging from the basic optically pure salt to a specific crystalline form and a method of coordinated delivery—were obvious to a person of ordinary skill in the art at the time of the inventions.
  • A final question will be one of claim scope: The interpretation of terms like "optically pure" ('504 patent) and what it means for an XRPD pattern to be "substantially in accordance with" a reference figure ('085 patent) will be critical. The court’s construction of these terms may determine the outcome of the infringement analysis.