PTAB

IPR2013-00368

Amneal Pharmaceuticals LLC v. Supernus Pharmaceuticals Inc

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Key Events
Petition

1. Case Identification

2. Patent Overview

  • Title: Once Daily Formulations of Tetracyclines
  • Brief Description: The ’740 patent relates to once-daily oral pharmaceutical compositions of the antibiotic doxycycline. The claimed compositions are formulated to provide specific steady-state blood levels (0.1 µg/ml to 1.0 µg/ml) and consist of a 30 mg immediate-release (IR) portion and a 10 mg delayed-release (DR) portion.

3. Grounds for Unpatentability

Ground 1: Obviousness over Ashley - Claims 1, 2, 5-15, and 19-22 are obvious over the '932 publication.

  • Prior Art Relied Upon: Ashley (International Publication No. WO 02/080932, “the ’932 publication”), which incorporates by reference the ’854 application (U.S. Appl. No. 60/281,854).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the ’932 publication taught all key limitations of independent claims 1 (composition) and 19 (method of treatment). Ashley allegedly disclosed oral, once-daily doxycycline compositions that achieve the claimed steady-state blood levels (0.1 to 1.0 µg/ml) for treating acne rosacea. The reference also taught combining immediate-release (IR) and delayed-release (DR) agents in a 40 mg total doxycycline dosage. Petitioner contended that Ashley’s preference for releasing at least 50% of the drug in the upper GI tract suggests IR:DR ratios of at least 50:50. A POSA would have allegedly arrived at the claimed 75:25 ratio (30mg IR:10mg DR) through routine experimentation and optimization of this known formulation.
    • Expectation of Success: A POSA would have had a high expectation of success because the ’932 publication disclosed all necessary components and parameters, including the drug, dosage form, release profile characteristics, total daily dose, and therapeutic application. Optimizing the specific ratio of IR to DR components was presented as a predictable and routine task in pharmaceutical formulation.
    • Key Aspects: Petitioner’s argument centered on the principle that selecting a specific ratio from a known and suggested range in the prior art constitutes obviousness, especially when achieving that ratio required only routine experimentation without producing unexpected results.

Ground 2: Obviousness over Ashley in view of Sheth - Claims 1, 2, 5-15, and 19-22 are obvious over the '932 publication in view of the '748 patent.

  • Prior Art Relied Upon: Ashley (’932 publication) and Sheth (Patent 5,348,748).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that even if Ashley alone did not render the claims obvious, the combination with Sheth did. The ’932 publication provided the foundational teaching of a 40 mg, once-daily doxycycline composition with IR and DR components for treating rosacea. Sheth, which addresses once-daily delivery systems for minocycline (a closely related tetracycline antibiotic), was cited for its explicit teaching of IR:DR ratios. Sheth disclosed pulsatile release formulations comprising 51 to 80 parts by weight quick-release granules and 20 to 49 parts by weight coated (delayed-release) granules, a range that directly encompasses the claimed 75:25 ratio.
    • Motivation to Combine: A POSA would combine Ashley with Sheth to improve the controlled-release characteristics of the doxycycline formulation. Since minocycline and doxycycline are structurally and functionally similar tetracyclines, a POSA would have been motivated to apply the optimized IR:DR ratio from Sheth to the doxycycline formulation in Ashley to achieve a predictable and desirable delivery profile.
    • Expectation of Success: Success was expected because both references concern oral, once-daily formulations of the same class of drugs, use IR and DR components, and aim to achieve stable therapeutic blood levels. Applying Sheth's established ratio system to doxycycline was argued to be a straightforward substitution with predictable results.

Ground 3: Obviousness over Ashley and Sheth - Claims 1, 2, 5-15, and 22 are obvious over the '106 publication in view of the '748 patent.

  • Prior Art Relied Upon: Ashley (International Publication No. WO 02/083106, “the ’106 publication”) and Sheth (Patent 5,348,748).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground presented an alternative primary reference but relied on the same combination logic as Ground 2. The ’106 publication, another reference to Ashley, also taught once-daily oral doxycycline compositions using IR and DR components to achieve sub-antimicrobial steady-state blood levels. Petitioner argued this reference similarly suggests a higher proportion of IR agent. The Sheth patent was again combined to provide the specific, narrow range of IR:DR ratios (51-80:20-49) that includes the claimed 75:25 ratio, thereby rendering the specific claimed dosage split obvious.
    • Motivation to Combine: The motivation was identical to that in Ground 2. A POSA would seek to enhance the release profile of the doxycycline formulation described in the ’106 publication by incorporating the successful and well-defined IR:DR ratios for a similar tetracycline taught in Sheth.
    • Expectation of Success: The rationale for expecting success was the same as in Ground 2, based on the close technical parallels between the drugs, formulations, and objectives disclosed in the combined references.

  • Additional Grounds: Petitioner asserted an additional obviousness challenge against claims 19-21 based on the combination of the ’106 publication, the ’748 patent, and Webster (a 2001 journal article), where Webster was used to provide further evidence for the known method of treating rosacea with low-dose doxycycline.

4. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1, 2, 5-15, and 19-22 of the ’740 patent as unpatentable.