PTAB

IPR2017-01648

Aurobindo Pharma USA Inc v. Andrx Labs LLC

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1. Case Identification

2. Patent Overview

  • Title: Controlled Release Metformin Compositions
  • Brief Description: The ’866 patent discloses once-daily, controlled-release oral dosage forms of metformin for treating non-insulin-dependent diabetes. The invention is characterized by specific pharmacokinetic parameters, particularly a mean time to maximum plasma concentration (Tmax) of 5.5 to 7.5 hours following administration with an evening meal.

3. Grounds for Unpatentability

Ground 1: Anticipation over Chen - Claims 1-25 are anticipated by Chen (WO 00/12097).

  • Prior Art Relied Upon: Chen (International Publication No. WO 00/12097).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the metformin tablets disclosed in Chen’s Example 1 are structurally and compositionally identical to those described in the ’866 patent. This identity extends to the core components (metformin, binder, enhancer), the sustained-release membrane coating, and the presence of two laser-drilled passageways for drug release. Although Chen's tablet also contains a minor amount of glipizide, Petitioner asserted this is not excluded by the "comprising" transitional phrase used in claim 1 of the ’866 patent.
    • Key Aspects: Petitioner contended that because Chen’s tablet is physically identical and exhibits the same in vitro dissolution profile as required by the dependent claims of the ’866 patent, the claimed in vivo pharmacokinetic parameters (Tmax, Cmax, AUC) are an inherent property of Chen's disclosed formulation. Therefore, Chen was argued to inherently anticipate all limitations of claims 1-25.

Ground 2: Anticipation over Timmins - Claims 1-3 are anticipated by Timmins (WO 99/47128).

  • Prior Art Relied Upon: Timmins (International Publication No. WO 99/47128).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that Timmins discloses a once-daily, controlled-release metformin formulation for administration after dinner. While Timmins explicitly states a median Tmax of 5 hours within a range of 4-8 hours, Petitioner, citing a prior Federal Circuit analysis of the same reference, argued that the raw data in Timmins teaches a mean Tmax that must fall between 4.67 and 6.33 hours.
    • Key Aspects: This taught mean Tmax range overlaps with and therefore anticipates the specific Tmax ranges recited in claim 1 (5.5-7.5 hours), claim 2 (6.0-7.0 hours), and claim 3 (5.5-7.0 hours) of the ’866 patent. The argument hinges on the assertion that the calculated mean Tmax from Timmins' data falls within the patented ranges.

Ground 3: Obviousness over Cheng and Timmins - Claims 1-25 are obvious over Cheng (WO 99/47125) in view of Timmins (WO 99/47128).

  • Prior Art Relied Upon: Cheng (International Publication No. WO 99/47125) and Timmins (International Publication No. WO 99/47128).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Cheng discloses a controlled-release metformin tablet with a nearly identical physical structure and composition to that claimed in the ’866 patent. However, Cheng’s formulation provides a higher Tmax of 8-12 hours. The secondary reference, Timmins, teaches a similar controlled-release metformin formulation but with a lower, more desirable mean Tmax of 4.67-6.33 hours. The only element missing from Cheng to arrive at the invention is the lower Tmax range taught by Timmins.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine these teachings to lower the Tmax of Cheng's formulation. The motivation, previously articulated by the Federal Circuit, would be to gain the known benefits of an earlier Tmax, such as improved patient compliance through reduced dosing frequency and convenience, and to create a product with a pharmacokinetic profile closer to the industry standard drug.
    • Expectation of Success: A POSA would have a high expectation of success because achieving the lower Tmax would involve only routine and predictable modifications. For example, a POSA would know that increasing the drug's release rate—by drilling an additional hole in Cheng’s tablet to match the two-hole embodiment of the ’866 patent—would lower the Tmax into the range taught by Timmins. Petitioner noted the patent's own prosecution history admitted such formulation adjustments were routine experimentation.

4. Key Technical Contentions (Beyond Claim Construction)

  • Inherency of Pharmacokinetic (PK) Parameters: A central technical contention across all grounds was that the claimed PK parameters are not independently patentable features but are the inherent, empirical result of a tablet's physical composition, structure, and in vitro release rate. Petitioner argued that if a prior art reference discloses a structurally identical formulation, it inherently discloses the resulting PK profile, regardless of whether that profile was explicitly measured or reported.
  • Calculation of Mean from Median Tmax: For the grounds involving Timmins, Petitioner's technical argument relied on the assertion that a POSA would be able and motivated to calculate the range of possible mean Tmax values from the raw data in Timmins, even though the reference itself only expressly disclosed a median Tmax.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-25 of the ’866 patent as unpatentable.