InnoPharma Licensing LLC v. AstraZeneca Ab

1. Case Identification

• Case #: IPR2017-00905
• Patent #: 8,466,139
• Filed: February 17, 2017
• Petitioner(s): InnoPharma Licensing, LLC
• Patent Owner(s): AstraZeneca Ab
• Challenged Claims: 1, 3, 10, 11, 13, and 20

2. Patent Overview

• Title: Method of Treating Breast Cancer
• Brief Description: The ’139 patent relates to a method of treating hormone-dependent breast cancer using a specific sustained-release formulation of fulvestrant. The claims are directed to a method of treatment involving intramuscular (IM) injection of a formulation containing fulvestrant and a specific combination of four excipients (castor oil, ethanol, benzyl alcohol, and benzyl benzoate) that achieves a specified minimum blood plasma concentration for at least two or four weeks.

3. Grounds for Unpatentability

Ground 1: Claims 1, 3, 10, 11, 13, and 20 are obvious over Howell.

• Prior Art Relied Upon: Howell (a 1996 journal article on the pharmacokinetics and anti-tumor effects of fulvestrant).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Howell taught the core elements of the claimed method, including treating breast cancer with a 50 mg/ml fulvestrant formulation in a castor oil-based vehicle via monthly IM injections, which resulted in the claimed sustained blood plasma concentrations (≥2.5 ng/ml for at least four weeks). While Howell did not disclose the exact four-excipient combination, Petitioner argued that arriving at the claimed formulation was a matter of routine optimization for a person of ordinary skill in the art (POSA).
  • Motivation to Combine: Not a combination ground, but Petitioner argued a POSA would be motivated to develop the specific claimed formulation to replicate the "excellent" and "promising" clinical results reported in Howell, which showed a 69% response rate in tamoxifen-resistant patients.
  • Expectation of Success: A POSA would have a reasonable expectation of success in developing the claimed formulation. This would involve routine solubility screening and the selection of well-known, FDA-approved co-solvents (ethanol, benzyl alcohol, and benzyl benzoate) known to enhance steroid solubility in castor oil, all used within previously established safe concentration ranges for IM injections.

Ground 2: Claims 1, 3, 10, 11, 13, and 20 are obvious over Howell in view of McLeskey.

• Prior Art Relied Upon: Howell (a 1996 journal article) and McLeskey (a 1998 journal article on tamoxifen-resistant cancer cells).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner contended this combination disclosed every limitation of the challenged claims. Howell provided the method of treatment, the promising clinical endpoint, the target drug concentration (50 mg/ml), the castor oil vehicle, and the IM route of administration. McLeskey supplied the missing element: the exact formulation recited in the claims, including 50 mg/ml fulvestrant with 10% ethanol, 10% benzyl alcohol, 15% benzyl benzoate, and a sufficient amount of castor oil.
  • Motivation to Combine: A POSA, motivated by the successful clinical outcomes in Howell, would seek a suitable castor oil-based formulation capable of solubilizing fulvestrant at the required 50 mg/ml concentration. A literature search would have identified McLeskey as one of only two known formulations meeting this requirement and the only one using pharmaceutically acceptable excipient levels. Therefore, a POSA would have selected the McLeskey formulation to practice the method taught by Howell.
  • Expectation of Success: A POSA would have a high expectation of success. The combination did not require modification, but rather the direct application of McLeskey's pre-existing, complete formulation to Howell's successful clinical method. Since castor oil is the rate-limiting excipient for drug release in both Howell's and McLeskey's formulations, a POSA would expect that administering the McLeskey formulation via IM injection would achieve the sustained therapeutic blood levels reported in Howell.

Ground 3: Claims 1, 3, 10, 11, 13, and 20 are obvious over Howell, McLeskey, and O'Regan.

• Prior Art Relied Upon: Howell (a 1996 journal article), McLeskey (a 1998 journal article), and O'Regan (a 1998 journal article on antiestrogens).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground reinforced the rationale for using an IM route of administration. While Howell already used IM injections in humans successfully, O'Regan provided an explicit, unequivocal statement that "clinically, [fulvestrant] must be given by depot intramuscular injection because of low oral potency." This teaching further solidified the combination of Howell's method with McLeskey's formulation.
  • Motivation to Combine: O'Regan, which cited Howell's promising results, would confirm to a POSA that IM administration is the necessary and mandatory clinical route for fulvestrant. This would eliminate any consideration of other administration routes (like the subcutaneous route used in McLeskey's mice studies) and motivate a POSA to administer the McLeskey formulation intramuscularly as taught by Howell and mandated by O'Regan.
  • Expectation of Success: O'Regan's explicit teaching strengthened the expectation that IM administration of the McLeskey formulation in humans was the correct and only viable clinical approach, thereby increasing the overall expectation of success.

4. Key Claim Construction Positions

• Petitioner adopted the broadest reasonable interpretation for claim terms, consistent with constructions from a related IPR on the parent ’680 patent.
• "achieves" / "attained": Petitioner proposed construing these terms to mean "the concentration of fulvestrant in a patient's blood plasma is at or above the specified minimum concentration for the specified time period." This construction frames the pharmacokinetic limitations as minimum performance thresholds.

5. Key Technical Contentions (Beyond Claim Construction)

• McLeskey Was Not a "Treatment Failure": Petitioner refuted the Patent Owner's characterization of McLeskey as a failure. It argued that fulvestrant performed exactly as intended in the study—to block estrogen receptors as a control—allowing researchers to confirm that tumor growth was stimulated by a different pathway (FGF), which was the study's primary goal.
• Excipient Combination Was Not Unpredictable: Petitioner contended that the claimed four-excipient combination was conventional, not surprising. It cited evidence that castor oil was a preferred vehicle for steroids and that ethanol, benzyl alcohol, and benzyl benzoate were well-known co-solvents commonly used to enhance steroid solubility in oil-based formulations, all within FDA-approved concentration ranges.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that this petition was substantially different from a previously filed Mylan IPR and should not be denied under §325(d). Key distinctions included: (1) presentation of two entirely new grounds of unpatentability (Grounds 1 and 3); (2) use of a different analytical starting point for the obviousness analysis (Howell as the primary reference, not McLeskey); and (3) introduction of new evidence, including declarations from one of McLeskey’s authors, to cure deficiencies the Board identified in the Mylan petition.

7. Relief Requested

• Petitioner requested institution of inter partes review and cancellation of claims 1, 3, 10, 11, 13, and 20 of the ’139 patent as unpatentable under 35 U.S.C. § 103.