DCT

2:17-cv-00630

Aptalis Pharma US Inc v. Zydus Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:17-cv-00630, D.N.J., 01/30/2017
  • Venue Allegations: Venue is asserted based on two of the Defendant entities being organized and having their principal places of business in New Jersey, and on the basis that New Jersey is a likely destination for the accused generic products upon FDA approval.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic mesalamine suppository constitutes an act of infringement of three patents covering specific pharmaceutical formulations for such suppositories.
  • Technical Context: The technology concerns pharmaceutical formulations for rectal suppositories containing the active ingredient mesalamine, which is used to treat ulcerative proctitis, a form of inflammatory bowel disease.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendants’ submission of ANDA No. 208953 to the FDA. As part of the ANDA process, Defendants filed a "Paragraph IV certification," asserting that Plaintiff's Orange Book-listed patents are invalid, unenforceable, or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2007-06-08 Earliest Priority Date for '384, '083, and '051 Patents
2009-06-02 U.S. Patent No. 7,541,384 Issued
2012-07-10 U.S. Patent No. 8,217,083 Issued
2013-05-07 U.S. Patent No. 8,436,051 Issued
2016-12-16 Date on or before which Defendants submitted ANDA No. 208953
2017-01-30 Complaint Filing Date

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

U.S. Patent No. 7,541,384 - Mesalamine Suppository

Issued June 2, 2009

The Invention Explained

  • Problem Addressed: The patent describes a need to improve patient comfort for users of mesalamine suppositories. It notes that a currently marketed 1-gram mesalamine suppository is of a "substantial size (3 g)," which can be uncomfortable for patients requiring treatment for conditions like active ulcerative proctitis (’384 Patent, col. 2:8-14).
  • The Patented Solution: The invention is a smaller, more comfortable suppository that maintains the required therapeutic dose. The inventors discovered that by using mesalamine powder with a higher "tap density," the viscosity of the molten suppository base during manufacturing could be decreased. This allows for a higher concentration of the drug to be loaded into a smaller total volume, resulting in a physically smaller suppository without compromising the dosage (’384 Patent, col. 2:25-33).
  • Technical Importance: This formulation technology enabled the development of a suppository that could be therapeutically equivalent to existing products but significantly smaller and potentially more comfortable, a key consideration for improving patient adherence to treatment regimens.

Key Claims at a Glance

The complaint asserts infringement of one or more claims without specification (Compl. ¶ 23). Independent claim 1 is representative and includes the following key elements:

  • A mesalamine rectal suppository comprising from about 850 to about 1150 mg of mesalamine and a fatty base;
  • Wherein the mesalamine has a tap density ranging from about 600 to about 800 g/L;
  • The drug load of the suppository ranges from 35% to 46%; and
  • The suppository releases at least 75% by weight of the mesalamine within 2 hours of dissolution under specific test conditions (USP Apparatus #2 at 40° C., 125 rpm paddle speed, in a specific phosphate buffer).

U.S. Patent No. 8,217,083 - Mesalamine Suppository

Issued July 10, 2012

The Invention Explained

  • Problem Addressed: As with the '384 patent, this patent addresses the need for mesalamine suppositories that provide "increased comfort of use" compared to existing larger formulations (’083 Patent, col. 2:8-11).
  • The Patented Solution: The patent, which is a continuation-in-part of the application leading to the '384 Patent, similarly discloses using mesalamine with a high tap density to reduce the viscosity of the molten base during manufacturing. This enables the creation of a smaller suppository for a given dose by allowing a higher drug concentration. The specification also explicitly describes embodiments for different dosage strengths, including a 500 mg version (’083 Patent, col. 2:15-32, col. 2:40-45).
  • Technical Importance: The invention provided a formulation platform that could be adapted for various dosage strengths of mesalamine, expanding the applicability of the comfort-enhancing technology.

Key Claims at a Glance

The complaint asserts infringement of one or more claims without specification (Compl. ¶ 42). Independent claim 1 is representative and includes the following key elements:

  • A mesalamine rectal suppository comprising mesalamine and an oily or fatty base;
  • Wherein the mesalamine has a tap density ranging from about 600 to about 800 g/L;
  • The suppository has a drug load ranging from 35% to 50%; and
  • The suppository releases at least about 75% by weight of the mesalamine within 2 hours of dissolution under specific test conditions.

U.S. Patent No. 8,436,051 - Mesalamine Suppository

Issued May 7, 2013

  • Technology Synopsis: This patent, also in the same family, introduces an additional physical parameter for optimizing the suppository: the surface area of the mesalamine particles. The inventors disclose the counterintuitive finding that for these formulations, a lower particle surface area can lead to a faster rate of drug dissolution (’051 Patent, col. 2:32-39). This provides an additional formulation strategy to control the drug release profile while still enabling a smaller, more comfortable suppository.
  • Asserted Claims: The complaint asserts infringement of one or more claims (Compl. ¶ 61). Independent claims include 1, 15, 18, 19, 33, 36, 42, and 43.
  • Accused Features: The complaint alleges that the formulation of Defendants' proposed generic 1000 mg mesalamine suppository, including its physical properties like particle surface area and dissolution profile, infringes the patent (Compl. ¶¶ 59-63).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Zydus's Proposed Product," a generic 1000 mg mesalamine rectal suppository for which Defendants submitted ANDA No. 208953 to the FDA for marketing approval (Compl. ¶ 11).

Functionality and Market Context

  • The product is a generic drug intended to be therapeutically equivalent to the brand-name CANASA® 1000 mg suppository, which is approved for the treatment of active ulcerative proctitis (Compl. ¶¶ 11-12). As an ANDA product, it is designed to serve as a lower-cost alternative to the branded version upon receiving FDA approval. The technical functionality relevant to the dispute lies in its composition and physical characteristics, such as the mesalamine dosage, the properties of the excipients, the tap density and surface area of the active ingredient, the total product weight, and its resulting dissolution profile (Compl. ¶¶ 22-25, 42-44, 61-63). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that the submission of the ANDA is an act of infringement under 35 U.S.C. § 271(e)(2) and that the future manufacture and sale of the product would constitute direct and indirect infringement. The allegations are made on information and belief pending discovery of the specifics of the ANDA filing.

U.S. Patent No. 7,541,384 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A mesalamine rectal suppository comprising from about 850 to about 1150 mg of mesalamine and a fatty base The complaint alleges Zydus's Proposed Product is a 1000 mg mesalamine suppository, which falls within the claimed dosage range, and that it is formulated with a base. ¶¶ 11, 23-24 col. 14:9-11
wherein the mesalamine has a tap density ranging from about 600 to about 800 g/L On information and belief, the complaint alleges the mesalamine used in the Proposed Product has a tap density meeting this limitation. ¶¶ 23-24 col. 14:12-14
the drug load of the suppository ranges from 35% to 46% On information and belief, the complaint alleges the formulation of the Proposed Product results in a drug load percentage that falls within the claimed range. ¶¶ 23-24 col. 14:14-16
and the suppository releases at least 75% by weight of the mesalamine within 2 hours of dissolution as measured with USP Apparatus #2 at 40° C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5 As a proposed generic equivalent, the complaint alleges on information and belief that the Proposed Product's dissolution profile meets the requirements of this limitation. ¶¶ 23-24 col. 14:16-22

U.S. Patent No. 8,217,083 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A mesalamine rectal suppository comprising mesalamine and an oily or fatty base The complaint alleges Zydus's Proposed Product is a mesalamine suppository formulated with a base. ¶¶ 11, 42-43 col. 14:10-11
wherein the mesalamine has a tap density ranging from about 600 to about 800 g/L On information and belief, the complaint alleges the mesalamine used in the Proposed Product has a tap density meeting this limitation. ¶¶ 42-43 col. 14:12-14
the suppository has a drug load ranging from 35% to 50% On information and belief, the complaint alleges the formulation of the Proposed Product results in a drug load percentage that falls within this broader claimed range. ¶¶ 42-43 col. 14:15-16
and the suppository releases at least about 75% by weight of the mesalamine within 2 hours of dissolution as measured with USP Apparatus #2 at 40° C... As a proposed generic equivalent, the complaint alleges on information and belief that the Proposed Product's dissolution profile meets the requirements of this limitation. ¶¶ 42-43 col. 14:17-23

Identified Points of Contention

  • Evidentiary Questions: The dispute will likely center on factual evidence obtained during discovery. A primary question is whether testing of Defendants' product will confirm that it actually meets the specific numerical limitations recited in the claims, including the mesalamine tap density, the final drug load percentage, and the dissolution rate under the precise conditions specified in the patents.
  • Scope Questions: The claims in the asserted patents rely on specific numerical ranges. The interpretation of the word "about" preceding these ranges may become a point of contention, raising the question of how much deviation from the stated values is permissible while still falling within the scope of the claims.

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 technology, certain terms are likely to be central.

The Term: "tap density ranging from about 600 to about 800 g/L"

’384 Patent, Claim 1

  • Context and Importance: This term is a cornerstone of the asserted patents, as the specific tap density is disclosed as the key to achieving the desired reduction in viscosity and suppository size. Infringement will depend entirely on whether the accused product's mesalamine falls within this range. Practitioners may focus on this term because the scope of "about" could be dispositive.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of the word "about" itself suggests the patentee did not intend the range to be strictly limited to 600-800 g/L. An argument could be made that it covers values that are technically equivalent or reflect standard measurement variability.
    • Evidence for a Narrower Interpretation: The specification provides specific examples of mesalamine lots with measured tap densities of 0.68 g/L and 0.72 g/L (’384 Patent, Table 8). A party could argue these examples anchor the meaning of the range, and "about" should not extend far beyond these demonstrated values.

The Term: "suppository releases at least about 75% by weight of the mesalamine within 2 hours of dissolution as measured with USP Apparatus #2..."

’384 Patent, Claim 1

  • Context and Importance: This functional limitation defines the required performance of the suppository. As a proposed bioequivalent product, the accused suppository is expected to have a similar dissolution profile, but proof of infringement requires meeting the exact test conditions and results of the claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The term "at least about 75%" could be argued to encompass results that are slightly below 75% but still functionally equivalent and within the margin of experimental error for the specified test method.
    • Evidence for a Narrower Interpretation: The patent provides a detailed, multi-part test for measuring dissolution (’384 Patent, col. 4:26-45). A party could argue that this high level of specificity implies the numerical result of "75%" should be interpreted with precision, limiting the scope of "about."

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement on the basis that Defendants, by seeking approval for the indication claimed in the patents, know and intend that physicians and patients will use the generic product in an infringing manner upon its launch. This intent is allegedly evidenced by the proposed product label (Compl. ¶¶ 26, 45, 64).
  • Willful Infringement: Willfulness is alleged based on Defendants' pre-suit knowledge of the patents. The complaint states that Defendants were aware of the patents prior to filing the ANDA, as evidenced by their submission of Paragraph IV certifications for those patents to the FDA (Compl. ¶¶ 27, 46, 65).

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

  • A primary issue will be one of evidentiary proof: Will discovery and expert testing demonstrate that the physical properties of Zydus's proposed generic suppository—specifically its mesalamine tap density, final drug load percentage, and dissolution rate under the patents' specified conditions—fall squarely within the numerical ranges required by the asserted claims?
  • A second key issue will be one of claim construction: How will the court interpret the scope of the term "about" as it applies to the quantitative limitations for tap density and drug load? The court's definition will set the boundaries for the factual infringement analysis.
  • A third central question will concern validity: As indicated by their Paragraph IV certifications, Defendants will likely challenge the validity of the patents. The case may therefore turn on whether Defendants can prove by clear and convincing evidence that the claimed formulation properties were anticipated or rendered obvious by pharmaceutical science prior to the patents' priority date.