DCT

3:20-cv-00678

Amgen Inc v. Zydus Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:20-cv-00678, D.N.J., 01/21/2020
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Zydus is a New Jersey corporation and Defendant Cadila is subject to personal jurisdiction in the district through its business activities and its actions in concert with Zydus.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the heart failure drug Corlanor® constitutes an act of infringement of four patents directed to specific crystalline forms of the active ingredient, ivabradine hydrochloride.
  • Technical Context: The technology concerns pharmaceutical polymorphs—distinct crystalline structures of the same chemical compound—which can possess different physical properties critical for drug manufacturing, stability, and bioavailability.
  • Key Procedural History: This action was filed under the Hatch-Waxman Act, triggered by a "Paragraph IV Certification" letter dated December 5, 2019, in which Defendants asserted that the patents-in-suit are invalid, unenforceable, or will not be infringed by their proposed generic product. The complaint also discloses a co-pending action in the U.S. District Court for the District of Delaware involving the same patents and defendants.

Case Timeline

Date Event
2005-02-28 Earliest Priority Date for '649', '650', '996', and '842' Patents
2008-04-22 Issue Date for U.S. Patent No. 7,361,649
2008-04-22 Issue Date for U.S. Patent No. 7,361,650
2011-01-11 Issue Date for U.S. Patent No. 7,867,996
2011-02-01 Issue Date for U.S. Patent No. 7,879,842
2019-12-05 Date of Defendants' Paragraph IV Notice Letter
2020-01-21 Complaint Filing Date

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

U.S. Patent No. 7,361,649 - "β-Crystalline Form of Ivabradine Hydrochloride, a Process for Its Preparation and Pharmaceutical Compositions Containing It," Issued April 22, 2008

The Invention Explained

  • Problem Addressed: The patent's background section notes that while the synthesis of ivabradine hydrochloride was previously known, the prior art "does not specify the conditions for obtaining ivabradine in a form that exhibits [stable and reproducible] characteristics" (’649 Patent, col. 2:47-52). This lack of a well-defined, stable form presents challenges for consistent pharmaceutical manufacturing and storage.
  • The Patented Solution: The invention is a specific crystalline form of ivabradine hydrochloride, designated the "β-form," which is characterized by a unique powder X-ray diffraction (PXRD) pattern (’649 Patent, Abstract). The patent provides a detailed table of diffraction data that serves as a fingerprint to identify this specific polymorph (’649 Patent, col. 2:57-65, Table at col. 3:45-55).
  • Technical Importance: Obtaining an active pharmaceutical ingredient in a specific, stable, and reproducible crystalline form is crucial for ensuring consistent product quality, shelf-life, and bioavailability in a formulated drug product (’649 Patent, col. 2:38-46).

Key Claims at a Glance

  • The complaint does not specify which claims it asserts, stating infringement of "one or more claims" (Compl. ¶41). U.S. Patent No. 7,361,649 contains one independent claim.
  • Independent Claim 1:
    • A β-Crystalline form of ivabradine hydrochloride of formula (I)
    • exhibiting essentially the powder X-ray diffraction data specified in a table of 34 peaks defined by angle (2 theta), height, area, width, and interplanar distance.

U.S. Patent No. 7,361,650 - "γ-Crystalline Form of Ivabradine Hydrochloride, a Process for Its Preparation and Pharmaceutical Compositions Containing It," Issued April 22, 2008

The Invention Explained

  • Problem Addressed: Similar to the ’649 Patent, this patent addresses the need for a well-defined, stable, and processable crystalline form of ivabradine hydrochloride suitable for large-scale pharmaceutical production (’650 Patent, col. 2:40-53).
  • The Patented Solution: The invention is a different crystalline form of the same compound, designated the "γ-form." This form is distinguished from others by its own unique powder X-ray diffraction (PXRD) pattern, which is detailed in the specification (’650 Patent, Abstract; Table at col. 3:45-52).
  • Technical Importance: The discovery of a new, stable polymorph provides an alternative solid form of the drug, which may have different properties and offer advantages or flexibility in formulation and manufacturing (’650 Patent, col. 2:54-56).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" (Compl. ¶50). U.S. Patent No. 7,361,650 contains one independent claim.
  • Independent Claim 1:
    • A γ-Crystalline form of ivabradine hydrochloride of formula (I)
    • exhibiting essentially the powder X-ray diffraction data specified in a table of 33 peaks.

U.S. Patent No. 7,867,996 - "γ-Crystalline Form of Ivabradine Hydrochloride, a Process for Its Preparation and Pharmaceutical Compositions Containing It," Issued January 11, 2011

  • Technology Synopsis: This patent, which is subject to a terminal disclaimer over the ’650 Patent, also claims the γ-crystalline form of ivabradine hydrochloride. It defines the polymorph using a smaller subset of its characteristic PXRD peaks, potentially creating a different scope of protection (’996 Patent, Claims 1-2).
  • Asserted Claims: The complaint does not specify; independent claims are 1 and 2.
  • Accused Features: The presence of the γ-crystalline form of ivabradine hydrochloride in the Defendants' proposed generic product (Compl. ¶59).

U.S. Patent No. 7,879,842 - "Beta-Crystalline Form of Ivabradine Hydrochloride, a Process for Its Preparation and Pharmaceutical Compositions Containing It," Issued February 1, 2011

  • Technology Synopsis: This patent, subject to a terminal disclaimer over the ’649 Patent, also claims the β-crystalline form of ivabradine hydrochloride. It defines the polymorph using smaller subsets of its characteristic PXRD peaks (’842 Patent, Claims 1-2).
  • Asserted Claims: The complaint does not specify; independent claims are 1 and 2.
  • Accused Features: The presence of the β-crystalline form of ivabradine hydrochloride in the Defendants' proposed generic product (Compl. ¶68).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendants' "Proposed ANDA Product," which is a generic version of Corlanor® (ivabradine) 5 mg and 7.5 mg tablets, for which Defendants seek FDA approval via ANDA No. 213442 (Compl. ¶1).

Functionality and Market Context

The Proposed ANDA Product contains the active pharmaceutical ingredient ivabradine, a drug used to treat certain cases of chronic heart failure (Compl. ¶26, ¶31). The complaint alleges that the ANDA submission contains data intended to demonstrate the bioequivalence of the proposed generic product to Plaintiffs' approved Corlanor® product (Compl. ¶32). The central infringing functionality alleged is the presence of ivabradine in one of the patented crystalline forms (Compl. ¶33). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or sufficient detail to construct one. The infringement allegations are pleaded generally on "information and belief" and state that Plaintiffs have not yet received sufficient information from Defendants to meaningfully evaluate the basis for non-infringement (Compl. ¶46, ¶55, ¶64, ¶73).

The narrative theory of infringement is consistent for all four patents-in-suit. Plaintiffs allege that Defendants' submission of ANDA No. 213442, seeking approval to market a product containing a specific patented crystalline form of ivabradine hydrochloride before the patents expire, is a statutory act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶42, ¶51, ¶60, ¶69). The infringement is based on the alleged "presence in the Proposed ANDA Product of an ivabradine crystalline form as covered by one or more of the claims" of each respective patent (Compl. ¶41, ¶50, ¶59, ¶68). The factual basis for this allegation will depend on the analysis of the drug substance used in Defendants' Proposed ANDA Product.

  • Identified Points of Contention:
    • Scope Questions: A central issue for claim construction may be the interpretation of the term "essentially" as it modifies the list of PXRD peaks in the claims of the ’649 and ’650 Patents. The court may need to determine how much deviation from the recited diffraction data is permissible before a crystalline form is considered non-infringing. The narrower claims of the ’996 and ’842 Patents, which rely on fewer peaks, raise questions about whether those subsets of peaks are sufficient to uniquely identify the patented polymorphs.
    • Technical Questions: The primary factual dispute will be whether the crystalline form of ivabradine hydrochloride in the Defendants' Proposed ANDA Product actually exhibits the specific PXRD pattern(s) required by the asserted claims. This question will likely be resolved through discovery and competing analyses of the accused product by technical experts.

V. Key Claim Terms for Construction

  • The Term: "β-Crystalline form . . . exhibiting essentially the following powder X-ray diffraction data" (from ’649 Patent, Claim 1)

  • Context and Importance: This term defines the patented invention. The outcome of the infringement analysis for the ’649 and ’842 Patents hinges on whether the crystalline form in the accused product matches this definition. Practitioners may focus on this term because the word "essentially" introduces ambiguity into what would otherwise be a precise, data-driven limitation, creating a clear point of dispute over the claim's breadth.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Plaintiffs may argue that the term "essentially" is intended to cover minor, instrument-related, or otherwise immaterial variations in the measured PXRD data, and that infringement occurs so long as the accused product's diffraction pattern corresponds in all material respects to the claimed pattern.
    • Evidence for a Narrower Interpretation: Defendants may argue that the patent provides an exhaustive and highly precise 34-peak data table, and that "essentially" cannot be used to read the claim on a product that is missing characteristic peaks or shows significant, non-trivial shifts in peak positions, thereby representing a different, non-infringing polymorph.

  • The Term: "γ-Crystalline form . . . exhibiting essentially the following powder X-ray diffraction data" (from ’650 Patent, Claim 1)

  • Context and Importance: As with the β-form, this term is the definition of the invention claimed in the ’650 and ’996 Patents. Its construction will be dispositive for infringement of those patents.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Arguments similar to those for the β-form would apply, focusing on the intent to cover immaterial variations from the recited PXRD data.
    • Evidence for a Narrower Interpretation: Arguments similar to those for the β-form would apply, emphasizing the detailed 33-peak data table as the specific fingerprint of the invention, which cannot be ignored or significantly broadened by the word "essentially."

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement, stating that Defendants intend to "instruct healthcare providers to use the Proposed ANDA Product in accordance with the proposed product labeling" upon FDA approval (Compl. ¶43, ¶52, ¶61, ¶70). This instruction to administer the allegedly infringing tablets would form the basis for an inducement claim.
  • Willful Infringement: The complaint does not use the word "willful" but alleges that Defendants had knowledge of the patents-in-suit when they submitted the ANDA, as evidenced by their Paragraph IV certification (Compl. ¶45, ¶54, ¶63, ¶72). In the prayer for relief, Plaintiffs request a declaration that the case is "exceptional" under 35 U.S.C. § 285, which is the statutory basis for awarding attorneys' fees and is often predicated on findings of willful infringement or other litigation misconduct (Compl., Prayer for Relief ¶e).

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

  • A central issue will be one of claim construction: How will the court define the scope of the claims, particularly the meaning of the word "essentially" when applied to the extensive X-ray diffraction data that defines the patented polymorphs? The breadth of this term will be critical in determining the boundary between infringing and non-infringing crystalline forms.
  • The primary evidentiary question will be one of factual identity: Does the specific crystalline structure of ivabradine hydrochloride in Defendants' proposed generic product, as will be revealed through scientific testing during discovery, actually match the fingerprint defined by the asserted claims? The case will likely evolve into a technical dispute between experts analyzing competing crystallographic data.
  • A key procedural question is the impact of parallel litigation: How will the co-pending case in the District of Delaware, involving the same parties and patents, affect the proceedings in this New Jersey action? This raises potential issues of judicial economy and case management strategy for both parties and the courts.