Intas Pharmaceuticals Ltd v. Atossa Therapeutics Inc

1. Case Identification

• Case #: PGR2023-00043
• Patent #: 11,572,334
• Filed: August 18, 2023
• Petitioner(s): Intas Pharmaceuticals Ltd.
• Patent Owner(s): Atossa Therapeutics, Inc.
• Challenged Claims: 1-22

2. Patent Overview

• Title: Methods for making and using Endoxifen
• Brief Description: The ’334 patent is directed to oral pharmaceutical formulations comprising an endoxifen composition encapsulated in an enteric capsule. The composition must contain at least 90% by weight of the (Z)-isomer of endoxifen, and the patent includes claims for methods of administering these formulations to treat hormone-dependent disorders.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1, 2, 4, 15, and 20-22 by Ahmad

• Prior Art Relied Upon: Ahmad (Patent 9,333,190).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Ahmad anticipates every limitation of the independent claims (1 and 15). Ahmad explicitly teaches oral formulations of endoxifen, including methods to achieve Z-endoxifen purity of at least 90%. Ahmad further discloses that its endoxifen compositions can be encapsulated in enteric-coated capsules to protect the drug from stomach acid and ensure its release in the small intestine. For the method claims, Ahmad teaches oral administration for treating hormone-dependent breast disorders, including for patients who are tamoxifen-resistant.
  • Key Aspects: The core of this ground is that Ahmad, a single prior art patent, discloses all elements of the claimed invention, from the specific chemical isomer and purity to the exact delivery vehicle (enteric capsule) for the same therapeutic purpose.

Ground 2: Obviousness of Claims 5-8, 16, and 17 over Ahmad in view of Cole

• Prior Art Relied Upon: Ahmad (Patent 9,333,190) and Cole (a 2002 journal article titled "Enteric coated HPMC capsules designed to achieve intestinal targeting").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Ahmad teaches the foundational oral formulation of 90% (Z)-endoxifen in an enteric capsule. The challenged dependent claims add specific functional limitations regarding dissolution profiles (e.g., resistance to dissolution in acid for at least 2 hours and release in intestinal fluid). Petitioner argued that Cole, which describes standard enteric coating performance, explicitly teaches these very dissolution characteristics. Cole demonstrates that a standard enteric coating prevents drug release at low pH (pH 1.2) for over two hours but allows for rapid release at a higher pH (pH 6.8) consistent with the small intestine.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA), starting with Ahmad’s acid-sensitive endoxifen formulation, would be motivated to use a standard enteric coating as taught by Cole for its intended and well-known purpose: to protect the drug in the stomach and ensure its release in the intestine. Achieving the claimed dissolution profiles is not an inventive step but the inherent and expected result of using a conventional enteric coating.
  • Expectation of Success: Because Cole documents the well-understood and predictable performance of common enteric coatings on capsules, a POSITA would have had a high expectation of success in achieving the claimed release profiles for Ahmad’s formulation.

Ground 3: Obviousness of Claim 3 over Ahmad in view of Benameur

• Prior Art Relied Upon: Ahmad (Patent 9,333,190) and Benameur (a 2015 article titled "Enteric Capsule Drug Delivery Technology – Achieving Protection Without Coating").

• Core Argument for this Ground:

  • Prior Art Mapping: This ground targets claim 3, which specifies that the enteric capsule is "uncoated." While Ahmad teaches an enteric-coated capsule, Benameur discloses an alternative, commercially available technology: intrinsically enteric capsules that provide acid resistance without requiring an external coating.
  • Motivation to Combine: A POSITA would have been motivated to modify Ahmad's formulation by substituting the coated capsule with the uncoated intrinsic capsule taught by Benameur as a simple design choice. The motivations cited were to simplify the manufacturing process, avoid exposing the drug to heat during the coating process, and achieve the same functional outcome of enteric protection.
  • Expectation of Success: Benameur demonstrates that its uncoated capsules provide effective enteric protection and proper release, giving a POSITA a reasonable expectation of success when combining this capsule technology with Ahmad's endoxifen composition.

• Additional Grounds: Petitioner asserted additional obviousness challenges. Claims 9-13, reciting common excipients like fillers and lubricants, were alleged to be obvious over Ahmad in view of standard pharmaceutical references Stegemann and the Handbook of Pharmaceutical Excipients (HPE). Claims 14, 18, and 19, reciting dosage and pharmacokinetic parameters, were alleged to be obvious over Ahmad in view of clinical data published in Ahmad 2010 and Ahmad 2012.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be inappropriate. It contended that while Ahmad was listed as a reference during prosecution, the Examiner did not issue a single rejection and therefore did not substantively evaluate it. More importantly, Petitioner asserted significant new prior art not considered by the Examiner, including Cole, Benameur, Stegemann, and HPE, which are central to several grounds of unpatentability. Petitioner argued that these new references and the novel arguments presented in the petition raise substantial questions of patentability that were not before the Office during prosecution.

5. Relief Requested

• Petitioner requests institution of Post Grant Review and cancellation of claims 1-22 of the ’334 patent as unpatentable.