Actavis LLC v. Abraxis Bioscience LLC

1. Case Identification

• Case #: IPR2017-01104
• Patent #: Patent 8,138,229
• Filed: April 4, 2017
• Petitioner(s): Actavis LLC
• Patent Owner(s): Abraxis Bioscience, LLC
• Challenged Claims: 1-48

2. Patent Overview

• Title: Compositions and Methods of Delivery of Pharmacological Agents
• Brief Description: The ’229 patent discloses pharmaceutical compositions of nanoparticles comprising the anticancer drug paclitaxel and the protein albumin. The invention is directed to formulations for injection where the weight ratio of albumin to paclitaxel is about 9:1 and the particle size is less than about 200 nm.

3. Grounds for Unpatentability

Ground 1: Anticipation by Inherently Disclosed Ratio - Claims 1-19 and 21-48 are anticipated under 35 U.S.C. §102(b) over Desai.

• Prior Art Relied Upon: Desai (WO 1999/000113).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Desai anticipates every limitation of the challenged claims. Desai's Example 1 describes a process of combining 30 mg of paclitaxel with 270 mg of human serum albumin, which Petitioner asserted is an express or, alternatively, inherent disclosure of the claimed 9:1 weight ratio. Petitioner further argued that Desai teaches the remaining limitations of independent claim 1: the resulting nanoparticles have a typical diameter of 160-220 nm (meeting the "about 200 nm" limitation), the composition can be reconstituted in saline, and this formulation results in an albumin weight concentration of 4.5% (falling within the claimed "about 0.5% to about 5%" range).
  • Key Aspects: The central thrust of this ground was that Desai's disclosure of starting ingredient quantities is sufficient to disclose the final composition's ratio, an interpretation Petitioner supported by pointing to examples in the ’229 patent itself where ratios are calculated from starting materials.

Ground 2: Obviousness by Optimization of a Disclosed Formulation - Claims 1-19 and 21-48 are obvious over Desai.

• Prior Art Relied Upon: Desai (WO 1999/000113).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner contended that even if Desai does not anticipate, it renders the claims obvious. Desai discloses a range of albumin-paclitaxel ratios, including its preferred Capxol™ embodiment with a 13.3:1 ratio and other examples with ratios such as 9.8:1 and 12.9:1. Petitioner argued the claimed 9:1 ratio falls within the predictable range of formulations a person of ordinary skill in the art (POSITA) would explore based on Desai's teachings.
  • Motivation to Modify: Petitioner asserted that Desai provides explicit motivation for a POSITA to lower the albumin-to-paclitaxel ratio from the 13.3:1 disclosed for Capxol™. Desai teaches developing formulations with higher paclitaxel concentrations to "reduce the time of administration," "minimize patient discomfort," and potentially achieve a "higher response rate." Lowering the relative amount of albumin achieves this higher drug concentration.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success in making this modification. Desai described its formulations as having "inherent stability," and its Capxol™ embodiment was shown to have "unusually exceptional stability," suggesting to a POSITA that a modest reduction in the albumin ratio would not lead to a problematic loss of stability.

Ground 3: Obviousness over Combination of Art - Claims 1-19 and 21-48 are obvious over Desai in view of Kadima and Liversidge.

• Prior Art Relied Upon: Desai (WO 1999/000113), Kadima (WO 2000/006152), and Liversidge (Patent 5,399,363).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Kadima and Liversidge independently teach albumin-paclitaxel nanoparticle formulations and disclose weight ratio ranges that explicitly encompass the claimed 9:1 ratio. Liversidge disclosed a range of albumin-to-paclitaxel ratios from 0.01:9.99 to 9:1, and Kadima taught a paclitaxel-to-albumin range corresponding to an albumin-to-paclitaxel range of 0.5:1 to 10:1.
  • Motivation to Combine: A POSITA would combine the teachings of Kadima and Liversidge with Desai's nanoparticle formulations to optimize them. Kadima provides a strong, independent financial motivation to lower the albumin ratio by teaching that albumin is a "cost-limiting component" and an "expensive ingredient." A POSITA would therefore be motivated to reduce the amount of albumin in Desai's formulation to create a more commercially feasible product.
  • Expectation of Success: Because all three references address the same technical problem of stabilized paclitaxel delivery and suggest that optimizing component ratios is a routine matter, a POSITA would have reasonably expected success in applying the specific ratio ranges from Kadima and Liversidge to Desai's formulation.
• Additional Grounds: Petitioner asserted further obviousness challenges for claim 20 (requiring a multi-dose container) based on Desai in view of the Taxol® label, arguing it would have been obvious to package the improved formulation in the same manner as the existing commercial product.

4. Key Claim Construction Positions

• "weight ratio of albumin to paclitaxel in the composition": Petitioner argued this term must be construed to include the ratio of the starting ingredients used to make the composition, not just a ratio measured in the final product. This interpretation was based on examples in the ’229 patent specification where the ratio is explicitly described as "corresponding to" the starting materials.
• "a particle size of less than about 200 nm": Petitioner proposed that "about" includes at least a 10% variance, meaning particle sizes up to 220 nm are covered by the claim language. This construction was argued to be consistent with the patent’s examples and allows Desai's disclosed particle size range of 160-220 nm to meet the limitation.

5. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-48 of Patent 8,138,229 as unpatentable.