DCT

3:17-cv-07453

Duke University v. Alembic Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:17-cv-07453, D.N.J., 09/25/2017
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Alembic Pharmaceuticals Inc. maintains a "regular and established place of business" in Princeton, New Jersey, and committed an act of infringement in the district through its ANDA submission. Venue for the foreign defendants is based on their status as non-U.S. residents.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of LATISSE® brand bimatoprost ophthalmic solution constitutes an act of infringement of a patent covering methods of treating hair loss.
  • Technical Context: The technology involves the use of synthetic prostaglandin F analogs, a class of pharmaceutical compounds, for the topical treatment of hypotrichosis (inadequate hair), particularly of the eyelashes.
  • Key Procedural History: The complaint details prior litigation involving a parent patent (U.S. Patent No. 7,388,029), whose claims were found obvious by the U.S. Court of Appeals for the Federal Circuit. Plaintiffs allege that the claims of the patent-in-suit are narrower and overcome the deficiencies identified in the prior litigation by being specifically limited to prostaglandin compounds with an amide group at the C-1 position.

Case Timeline

Date Event
2000-03-31 U.S. Patent No. 9,579,270 Priority Date
2008-01-01 FDA Approval of LATISSE® (approximate date)
2017-02-28 U.S. Patent No. 9,579,270 Issue Date
2017-08-14 Plaintiffs' Receipt of Alembic's Paragraph IV Letter
2017-09-25 Complaint Filing Date

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

U.S. Patent No. 9,579,270 - "Compositions and Methods for Treating Hair Loss Using Non-Naturally Occurring Prostaglandins"

  • Patent Identification: U.S. Patent No. 9,579,270, "Compositions and Methods for Treating Hair Loss Using Non-Naturally Occurring Prostaglandins," issued February 28, 2017 (the "'270 Patent").

The Invention Explained

  • Problem Addressed: The patent's background section addresses the common problem of hair loss, noting that existing approved treatments have safety concerns and limited efficacy (’270 Patent, col. 1:29-2:22). It also notes that while naturally occurring prostaglandins have been proposed for hair growth, their administration can cause undesirable side effects like inflammation and smooth muscle contraction (’270 Patent, col. 3:9-22).
  • The Patented Solution: The invention claims to solve this problem by using specific, non-naturally occurring prostaglandin F analogs that are designed to selectively activate the FP receptor, which is associated with hair growth, without activating other receptors that could negate the desired effect or cause side effects (’270 Patent, Abstract; col. 3:24-34). This targeted approach is intended to provide the therapeutic benefit of promoting hair growth while minimizing adverse reactions associated with broader-acting prostaglandins (’270 Patent, col. 3:15-22).
  • Technical Importance: This approach was technically significant because it represented a shift from using naturally occurring, multi-receptor prostaglandins to using synthetic analogs engineered for receptor selectivity, aiming for a more favorable therapeutic profile in treating hair loss (Compl. ¶¶32-34, 53).

Key Claims at a Glance

  • The complaint asserts dependent claims 22 and 30, which rely on independent claim 17 (Compl. ¶¶35-36, 43).
  • Independent Claim 17 recites a method of growing hair with the following essential elements:
    • Topically applying to mammalian skin a safe and effective amount of a composition.
    • The composition contains an active ingredient, which is a prostaglandin F analog having a specific core chemical structure.
    • The structure requires a substituent R1 selected from a group including C(O)NHR3 (an amide).
    • The structure requires a substituent R2 to be a hydrogen atom.
    • The structure has a linker X and a terminal group Z, where Z is selected from a list of cyclic chemical groups.

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic bimatoprost ophthalmic solution, 0.03%, submitted for FDA approval under ANDA No. 210515 (Compl. ¶55).

Functionality and Market Context

  • The accused product is a generic version of Plaintiffs' LATISSE® product, which is indicated for the treatment of hypotrichosis of the eyelashes (Compl. ¶¶39, 55). Its active ingredient is bimatoprost, described as a synthetic analog of Prostaglandin F2α (PGF2α) (Compl. ¶31). The complaint highlights two structural differences between bimatoprost and natural PGF2α: bimatoprost contains an ethyl amide at the C-1 position instead of a carboxylic acid, and it has a shortened omega chain with a phenyl group at the C-17 position (Compl. ¶31). The complaint includes a chemical structure diagram illustrating bimatoprost (Compl. ¶30).
  • Plaintiffs allege that LATISSE® has been a commercially successful product, with net sales exceeding $70 million annually since its launch in 2009 (Compl. ¶41).

IV. Analysis of Infringement Allegations

’270 Patent Infringement Allegations

Claim Element (from Independent Claim 17) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of growing hair, wherein the method comprises topically applying to mammalian skin a safe and effective amount of a composition comprising: The accused product is a 0.03% bimatoprost ophthalmic solution intended for application to the eyelid margin for the treatment of hypotrichosis of the eyelashes. ¶¶39, 81 col. 1:1-2:2
A) an active ingredient selected from the group consisting of a prostaglandin F analog of the following structure: [chemical structure] The active ingredient is bimatoprost, which the complaint alleges is a synthetic PGF2α analog and provides a corresponding chemical structure. A visual in the complaint depicts this structure. ¶¶30, 31, 37 col. 7:35-64
wherein R1 is selected from the group consisting of C(O)NHOH, C(O)NHR3, and C(O)NHS(O)2R4 Bimatoprost is alleged to have an R1 substituent of C(O)NHR3, specifically an ethyl amide where R3 is CH2CH3. ¶¶31, 37 col. 8:15-18
R2 is a hydrogen atom The structure of bimatoprost contains a hydrogen atom at the R2 position. ¶30 col. 8:21-22
Z is selected from the group consisting of a...aromatic group... Bimatoprost is alleged to have a phenyl group at the C-17 position, which corresponds to the claimed Z group. ¶¶31, 37 col. 8:48-53
  • Identified Points of Contention:
    • Scope Questions: The primary infringement dispute may center on claim construction. A potential question is whether bimatoprost, which the complaint notes binds to a "prostamide receptor" rather than the "FP receptor" targeted by natural PGF2α (Compl. ¶32), can be properly classified as a "prostaglandin F analog" as that term is used and defined in the patent.
    • Technical Questions: The complaint alleges that in bimatoprost, "X is CH2CH2; and Z is phenyl" (Compl. ¶37). A central evidentiary question will be whether the complete chemical structure of bimatoprost, including the linker between the core and the terminal phenyl group, corresponds to one of the specific options required by the claim's definition of X (’270 Patent, col. 8:41-46). The complaint makes a conclusory allegation on this point without providing a detailed structural comparison.

V. Key Claim Terms for Construction

  • The Term: "prostaglandin F analog"

  • Context and Importance: This term defines the class of compounds covered by the patent method. The infringement analysis depends entirely on whether bimatoprost, the active ingredient in the accused product, falls within the scope of this term. Practitioners may focus on this term because the complaint itself distinguishes the pharmacological activity of bimatoprost (binding to a "prostamide receptor") from that of natural PGF2α (binding to the "FP receptor"), raising the question of whether they belong to the same patent-defined class (Compl. ¶¶32-34).

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent provides a broad structural definition for suitable "prostaglandin F analogs" via a Markush group structure, which appears intended to encompass a wide range of synthetic variations (’270 Patent, col. 7:35-8:66).
    • Evidence for a Narrower Interpretation: The patent repeatedly refers to the invention in the context of activating the "FP receptor" (’270 Patent, col. 3:24-34). A defendant may argue that since bimatoprost allegedly does not bind to the FP receptor (Compl. ¶32), it cannot be a "prostaglandin F analog" within the meaning of the patent, regardless of structural similarity.

  • The Term: "growing hair"

  • Context and Importance: This term defines the result of the claimed method. Its definition is critical because it must map to the indication for which the accused product will be marketed and used. The complaint notes that in prior litigation on a related patent, the term "treating hair loss" was construed broadly (Compl. ¶46). The parties will likely dispute whether "growing hair" carries the same broad meaning or a more specific, limited one.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent abstract states the compositions can "arrest hair loss, reverse hair loss, and promote hair growth," suggesting a broad scope that could encompass increasing the length, thickness, or darkness of existing hair, consistent with the LATISSE® indication (Compl. ¶39; ’270 Patent, Abstract).
    • Evidence for a Narrower Interpretation: A defendant might argue that "growing hair" requires the initiation of new hair follicles or conversion from telogen to anagen phase, a potentially higher standard than merely enhancing the characteristics of existing hair.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement.
    • Inducement is alleged based on Defendants' future actions of providing a product label and instructions that will direct patients and healthcare providers to perform the patented method of topically applying bimatoprost to treat eyelash hypotrichosis. Knowledge is alleged based on the patent's listing in the FDA's Orange Book and the ANDA filing itself (Compl. ¶¶77, 80, 82).
    • Contributory infringement is alleged on the basis that bimatoprost is a material part of the invention, is not a staple article of commerce, and is especially made for the infringing use of growing eyelashes (Compl. ¶¶95, 98).
  • Willful Infringement: While not using the term "willful infringement" in a count heading, the complaint alleges that upon awareness of the patent, Defendants "either actually knew of the potential for infringement... or were willfully blind" (Compl. ¶83). It further seeks treble damages for any post-approval infringement (Compl. ¶101(d)), creating a basis for a willfulness claim predicated on pre-suit knowledge from the Orange Book listing and the ANDA filing process (Compl. ¶¶68, 77).

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

  • A core issue will be one of validity over the prior art: can the ’270 Patent's claims, which are narrowed to prostaglandin analogs with a C-1 amide group, successfully distinguish themselves from the prior art that led the Federal Circuit to invalidate the broader claims of the parent ’029 patent? The case may depend on whether this narrower scope is commensurate with the alleged "unexpected results" for C-1 amides.
  • A second central issue will be one of claim scope and pharmacological identity: does the term "prostaglandin F analog," as defined and used in the patent, encompass bimatoprost? This will require the court to decide if the patent's structural definition controls, or if the alleged functional difference in receptor binding (FP receptor vs. prostamide receptor) places bimatoprost outside the claimed class of compounds.