DCT

1:24-cv-01356

Aytu Biopharma Inc v. Granules Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01356, D. Del., 12/11/2024
  • Venue Allegations: Venue is asserted in the District of Delaware based on the Defendant being a Delaware corporation.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiffs’ ADZENYS XR-ODT® products constitutes an act of infringement of four U.S. patents related to extended-release amphetamine formulations.
  • Technical Context: The technology involves pharmaceutical compositions for treating Attention Deficit Hyperactivity Disorder (ADHD) using amphetamines complexed with ion-exchange resins to create orally disintegrating tablets that provide both immediate and extended release of the active ingredient.
  • Key Procedural History: The litigation was triggered by Defendant’s filing of ANDA No. 219800 with the U.S. Food and Drug Administration (FDA), which included a Paragraph IV certification alleging that Plaintiffs' patents are invalid and/or will not be infringed by the proposed generic products. The complaint also notes that the USPTO issued a Certificate of Correction for the '924 patent in 2017 to correct a patent term adjustment.

Case Timeline

Date Event
2005-10-21 U.S. Patent No. 8,840,924 Priority Date
2011-06-28 U.S. Patent Nos. 8,709,491, 9,017,731, & 9,265,737 Priority Date
2014-04-29 U.S. Patent No. 8,709,491 Issued
2014-09-23 U.S. Patent No. 8,840,924 Issued
2015-04-28 U.S. Patent No. 9,017,731 Issued
2016-02-23 U.S. Patent No. 9,265,737 Issued
2017-06-06 Certificate of Correction issued for '924 Patent
2024-10-31 Alleged ANDA No. 219800 Submission Date (on or before)
2024-11-01 Plaintiffs allegedly received notification of ANDA filing (no earlier than)
2024-12-11 Complaint Filing Date

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

U.S. Patent No. 8,709,491 - "Composition Comprising A Mixture Of Dextro- and Levo-Amphetamines Complexed With Ion-Exchange Resin Particles To Form Drug Resin Particles"

  • Patent Identification: U.S. Patent No. 8,709,491, "Composition Comprising A Mixture Of Dextro- and Levo-Amphetamines Complexed With Ion-Exchange Resin Particles To Form Drug Resin Particles," issued April 29, 2014. (Compl. ¶9)

The Invention Explained

  • Problem Addressed: The patent addresses the difficulty patients, particularly children, have in complying with ADHD treatment regimens that require multiple daily doses. It also notes that existing once-a-day solid dosage forms can be difficult to swallow, further complicating compliance. (’491 Patent, col. 1:33-61)
  • The Patented Solution: The invention is a pharmaceutical composition that combines two distinct populations of drug-resin particles. A first population is uncoated to provide immediate drug release, while a second population is covered with a delayed-release coating. This combination is designed to create a prolonged therapeutic effect from a single dose, characterized by an "escalating in vivo plasma concentration" of the active agent. (’491 Patent, Abstract; col. 1:28-32)
  • Technical Importance: This approach allows for the creation of a once-daily ADHD treatment in patient-friendly dosage forms, such as orally disintegrating tablets or liquid suspensions, intended to improve patient adherence compared to traditional pills. (’491 Patent, col. 2:51-60)

Key Claims at a Glance

  • The complaint asserts infringement of at least independent Claim 1. (Compl. ¶19)
  • Essential elements of Claim 1 include:
    • A pharmaceutical composition comprising a mixture of dextro- and levo-amphetamines complexed with ion-exchange resin particles to form drug resin particles,
    • wherein the composition comprises 20 to 50% of a first plurality of drug-resin particles that are uncoated,
    • and 50 to 80% of a second plurality of drug-resin particles that are coated with a delayed release coating.
  • The complaint states that Defendant’s actions would infringe "one or more claims of the '491 patent," reserving the right to assert additional claims. (Compl. ¶20)

U.S. Patent No. 8,840,924 - "Compositions And Methods Of Making Rapidly Dissolving Ionically Masked Formulations"

  • Patent Identification: U.S. Patent No. 8,840,924, "Compositions And Methods Of Making Rapidly Dissolving Ionically Masked Formulations," issued September 23, 2014. (Compl. ¶10)

The Invention Explained

  • Problem Addressed: Pharmaceutical compositions designed for rapid absorption in the mouth, such as orally disintegrating or chewable tablets, often present the active ingredient in a way that creates an "unpleasant texture or even an unpalatable taste," which can deter patient compliance. (’924 Patent, col. 2:40-44)
  • The Patented Solution: The invention is a compressed, orally disintegrating tablet that achieves both taste-masking and controlled release. It combines a drug that is ionically bound to a resin and coated with a controlled-release layer, with a "directly compressible, free-flowing pharmaceutical excipient." This excipient is specifically chosen to facilitate the rapid disintegration of the tablet in the mouth, thereby liberating the taste-masked drug-resin complex. (’924 Patent, Abstract; col. 3:13-16)
  • Technical Importance: The technology provides a method to formulate a controlled-release, taste-masked drug in a solid tablet that rapidly dissolves in the mouth, addressing a key challenge for pediatric and geriatric patients who may have difficulty swallowing conventional pills. (’924 Patent, col. 2:36-44)

Key Claims at a Glance

  • The complaint asserts infringement of at least independent Claim 1. (Compl. ¶25)
  • Essential elements of Claim 1 include:
    • A compressed, orally disintegrating, controlled release taste-masked pharmaceutical composition comprising:
    • a coated drug-ion-exchange resin complex and a directly compressible, free-flowing pharmaceutical excipient,
    • wherein the composition effectively masks an unpalatable taste,
    • wherein the coated drug-ion-exchange resin complex is coated with a controlled release coating,
    • and wherein the directly compressible, free-flowing pharmaceutical excipient aids in the liberation of the coated drug-resin complex in the mouth through disintegration.
  • The complaint reserves the right to assert infringement of additional claims. (Compl. ¶26)

U.S. Patent No. 9,017,731 - "Composition Comprising A Mixture Of Dextro- and Levo-Amphetamines Complexed With Ion-Exchange Resin Particles To Form Drug Resin Particles"

  • Patent Identification: U.S. Patent No. 9,017,731, "Composition Comprising A Mixture Of Dextro- and Levo-Amphetamines Complexed With Ion-Exchange Resin Particles To Form Drug Resin Particles," issued April 28, 2015. (Compl. ¶11)
  • Technology Synopsis: This patent, similar to the '491 patent, describes a pharmaceutical composition for once-daily ADHD treatment. The invention aims to solve patient compliance issues by providing a formulation with two populations of drug-resin particles—one uncoated and one coated—to achieve a prolonged release profile. The claims specify the composition by the percentage by weight of the amphetamines present in each of the two particle populations. (’731 Patent, Abstract; col. 1:28-32)
  • Asserted Claims: Independent Claim 1. (Compl. ¶31)
  • Accused Features: The Defendant's proposed generic products are alleged to infringe by containing a composition that meets the claimed weight percentages of amphetamines in uncoated and coated drug-resin particle populations. (Compl. ¶¶16, 32)

U.S. Patent No. 9,265,737 - "Pharmaceutical Composition Comprising Amphetamines Complexed With Ion-Exchange Resin Particles"

  • Patent Identification: U.S. Patent No. 9,265,737, "Pharmaceutical Composition Comprising Amphetamines Complexed With Ion-Exchange Resin Particles," issued February 23, 2016. (Compl. ¶12)
  • Technology Synopsis: This patent also discloses a pharmaceutical composition for ADHD treatment using amphetamines complexed with ion-exchange resins. The invention is directed at achieving a specific therapeutic effect by combining a population of immediate release drug-resin particles with a population of coated, delayed release particles. The claim defines the composition by the weight percentage of the total amphetamines that are present in each of the two populations. (’737 Patent, Abstract; col. 1:28-32)
  • Asserted Claims: Independent Claim 1. (Compl. ¶37)
  • Accused Features: The Defendant's proposed generic products are alleged to infringe by containing a composition with the claimed ratio of amphetamines in immediate-release and delayed-release particle populations. (Compl. ¶¶16, 38)

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are Defendant Granules' proposed generic versions of ADZENYS XR-ODT®, as described in ANDA No. 219800 submitted to the FDA. (Compl. ¶16)

Functionality and Market Context

  • The complaint identifies the accused products as "amphetamine extended-release orally disintegrating tablets" that would be available in multiple dosages. (Compl. ¶16). By seeking approval as generic versions of ADZENYS XR-ODT®, the complaint alleges that the products are intended to be therapeutic equivalents that replicate the functionality of Plaintiffs' patented drug, which was the first FDA-approved product of its kind for treating ADHD. (Compl. ¶¶13-14, 16). The filing of the ANDA is an alleged attempt to enter the market with a generic competitor prior to the expiration of the patents-in-suit, which are listed in the FDA's "Orange Book" in connection with the branded product. (Compl. ¶15)

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for analysis of infringement on an element-by-element basis. The infringement theory is based on the statutory act of filing an ANDA under 35 U.S.C. § 271(e)(2)(A), which seeks approval for a drug claimed in a patent before that patent’s expiration. (Compl. ¶20). The complaint alleges that the product described in the ANDA, if approved and marketed, will meet all limitations of the asserted claims.

No probative visual evidence provided in complaint.

'491 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition comprising a mixture of dextro- and levo-amphetamines complexed with ion-exchange resin particles to form drug resin particles... The ANDA product is alleged to be a pharmaceutical composition containing dextro- and levo-amphetamines bound to ion-exchange resin. ¶¶16, 19 col. 2:46-49
...wherein said composition comprises 20 to 50% of a first plurality of drug-resin particles that are uncoated... The ANDA product is alleged to contain a population of uncoated drug-resin particles that constitutes 20% to 50% of the total drug-resin particles. ¶¶16, 19 col. 4:54-55
...and 50 to 80% of a second plurality of drug-resin particles that are coated with a delayed release coating. The ANDA product is alleged to contain a second population of coated drug-resin particles that constitutes 50% to 80% of the total drug-resin particles. ¶¶16, 19 col. 4:56-57
  • Identified Points of Contention:
    • Scope Questions: A potential dispute may arise over the definition of "drug-resin particles." Further, the precise percentages of uncoated and coated particles will be a central factual question. A primary issue for the court will be whether the formulation described in Granules' confidential ANDA submission literally falls within the claimed 20-50% and 50-80% ranges.
    • Technical Questions: The nature of the "delayed release coating" on the second plurality of particles in the ANDA product may be scrutinized to determine if it meets the meaning of that term as understood in the patent.

'924 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compressed, orally disintegrating, controlled release taste-masked pharmaceutical composition comprising... The ANDA product is alleged to be a compressed tablet that disintegrates orally and provides taste-masking and controlled release of amphetamine. ¶¶16, 25 col. 2:45-54
...a coated drug-ion-exchange resin complex and a directly compressible, free-flowing pharmaceutical excipient... The ANDA product is alleged to contain both a coated drug-ion-exchange resin complex and a free-flowing, directly compressible excipient. ¶¶16, 25 col. 3:1-4
...wherein the composition effectively masks an unpalatable taste... The ANDA product's formulation is alleged to mask the taste of the amphetamine active ingredient. ¶¶16, 25 col. 2:40-44
...wherein the coated drug-ion-exchange resin complex is coated with a controlled release coating... The ANDA product's drug-resin complex is alleged to be coated with a material that controls the drug's release rate. ¶¶16, 25 col. 3:11-12
...and wherein the directly compressible, free-flowing pharmaceutical excipient aids in the liberation of the coated drug-resin complex in the mouth through disintegration. The excipient in the ANDA product is alleged to perform the function of facilitating the breakup of the tablet in the mouth to release the drug-resin complex. ¶¶16, 25 col. 3:13-16
  • Identified Points of Contention:
    • Scope Questions: A central question may be the construction of the functional limitation "aids in the liberation of the coated drug-resin complex in the mouth." The parties may dispute the mechanism and degree of "aid" required to meet this element.
    • Technical Questions: The court may need to determine whether the defendant's formulation "effectively masks an unpalatable taste" to a degree consistent with the patent's teachings. Additionally, evidence will be required to show that the excipient in the ANDA product actually performs the claimed function of aiding liberation through disintegration in the mouth.

V. Key Claim Terms for Construction

  • The Term: "delayed release coating" (’491 Patent, Claim 1)
  • Context and Importance: This term defines the essential characteristic of the second, larger population of drug-resin particles responsible for the extended-release profile. The infringement analysis will depend on whether the coating used in Granules' ANDA product qualifies as a "delayed release coating" under the patent's definition.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes the delayed release as potentially comprising a "triggered-release coating," which itself is defined broadly to include coatings that respond to pH changes or enzymes in the GI tract. (’491 Patent, col. 4:56-64; col. 9:14-25)
    • Evidence for a Narrower Interpretation: A defendant may argue the term should be limited by the specific examples provided, such as pH-triggered coatings like EUDRAGIT® L100 or diffusion barrier coatings like ethylcellulose, potentially narrowing the scope to exclude other types of controlled-release mechanisms. (’491 Patent, col. 4:59-64)
  • The Term: "directly compressible, free-flowing pharmaceutical excipient" (’924 Patent, Claim 1)
  • Context and Importance: This term is critical because it describes a key ingredient that enables the tablet to be manufactured via direct compression and to disintegrate rapidly. Practitioners may focus on this term because the defendant could argue its chosen excipient lacks one of these specific physical properties or does not perform the claimed function.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent does not define the term with particularity, suggesting it should be given its plain and ordinary meaning in the field of pharmaceutical formulation.
    • Evidence for a Narrower Interpretation: A party might argue that the term is implicitly limited by the functional requirement that the excipient "aids in the liberation of the coated drug-resin complex in the mouth through disintegration." This could narrow the term to only those excipients capable of achieving this specific result in the claimed context. (’924 Patent, col. 3:13-16)

VI. Other Allegations

  • Indirect Infringement: The complaint includes allegations that if Granules commercially makes, uses, or sells the generic products, it will induce and contribute to infringement by third parties, such as patients and doctors. (Compl. ¶20, ¶26, ¶32, ¶38) These allegations are predicated on the future commercialization of the product with accompanying labels and instructions for use.
  • Willful Infringement: The complaint alleges that Granules was aware of each patent-in-suit prior to filing its ANDA, as evidenced by its Paragraph IV certification regarding those patents. (Compl. ¶21, ¶27, ¶33, ¶39). Based on this alleged pre-suit knowledge, the complaint asserts that the infringement is willful and seeks a finding that the case is "exceptional" under 35 U.S.C. § 285, which would permit an award of attorney fees. (Compl. ¶22, ¶28, ¶34, ¶40)

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

  • A core issue will be one of compositional identity: does the formulation detailed in Granules’ confidential ANDA literally contain the specific ratios of coated versus uncoated (or immediate-release) drug-resin particles required by the asserted claims of the '491, '731, and '737 patents? The resolution of this issue will likely depend on expert analysis of the ANDA's chemistry, manufacturing, and controls (CMC) section.
  • A key evidentiary question will be one of functional performance: concerning the '924 patent, does the excipient used in Granules' proposed generic tablet perform the specific claimed function of "aid[ing] in the liberation of the coated drug-resin complex in the mouth through disintegration," or does its mechanism of action differ in a way that places it outside the scope of the claim?