Actavis LLC v. Abraxis Bioscience LLC

1. Case Identification

• Case #: IPR2017-01103
• Patent #: 7,923,536
• Filed: April 4, 2017
• Petitioner(s): Actavis LLC
• Patent Owner(s): Abraxsis Bioscience, LLC
• Challenged Claims: 1-16

2. Patent Overview

• Title: Compositions and Methods of Delivery of Pharmacological Agents
• Brief Description: The ’536 patent is directed to methods of treating cancer in a human by injecting a pharmaceutical composition of nanoparticles. The nanoparticles comprise the anticancer drug paclitaxel and a carrier comprising albumin, wherein the weight ratio of albumin to paclitaxel in the composition is about 1:1 to about 9:1.

3. Grounds for Unpatentability

Ground 1: Anticipation over Desai - Claims 1-16 are anticipated by Desai under 35 U.S.C. §102(b).

• Prior Art Relied Upon: Desai (International Publication No. WO 1999/000113).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Desai, a publication by the inventors of the ’536 patent, discloses every limitation of the challenged claims. Specifically, Example 1 of Desai describes a process for making albumin-paclitaxel nanoparticles by combining 30 mg of paclitaxel with 270 mg of human serum albumin, which Petitioner asserted is an explicit disclosure of the claimed 9:1 weight ratio. Desai further teaches that these particles have a typical diameter of 160-220 nm (meeting the "less than about 200 nm" limitation) and are intended for intravenous injection to treat cancers, including breast cancer. Petitioner contended this single reference therefore teaches a method of treating cancer with a composition meeting all structural and ratio limitations of independent claim 1 and the additional limitations of all dependent claims.
  • Key Aspects: The core of the anticipation argument relies on interpreting the claim term "weight ratio" to include the ratio of starting ingredients, which Petitioner argued is explicitly provided in Desai's "recipe."

Ground 2: Obviousness over Desai - Claims 1-16 are obvious over Desai under 35 U.S.C. §103.

• Prior Art Relied Upon: Desai (International Publication No. WO 1999/000113).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that even if Desai does not anticipate the claims, it renders them obvious. Desai discloses a preferred embodiment, Capxol™, with an albumin-paclitaxel ratio of 13.3:1, as well as other examples with ratios like 9.8:1 and 12.9:1. This established a known range of effective ratios close to the claimed 9:1. Petitioner asserted that the claimed ratio of about 9:1 falls within a range disclosed and suggested by Desai, establishing a prima facie case of obviousness.
  • Motivation to Combine: A POSITA would be motivated to modify Desai's 13.3:1 Capxol™ formulation to arrive at the claimed ratio of about 9:1. Desai explicitly teaches that it is desirable to develop formulations with higher concentrations of paclitaxel (i.e., a lower albumin-to-paclitaxel ratio) to reduce administration time, decrease infusion volume, and minimize patient discomfort. This provides a clear reason to reduce the amount of albumin relative to paclitaxel.
  • Expectation of Success: A POSITA would have reasonably expected success in creating a stable formulation with a 9:1 ratio. Desai describes its albumin-based formulations as having "inherent stability" and provides no indication that the 13.3:1 ratio is critical for stability. Given that Desai also discloses a working 9:1 example, a POSITA would expect that a modest reduction from 13.3:1 to 9:1 would maintain sufficient stability for therapeutic use.

Ground 3: Obviousness over Desai, Kadima, and Liversidge - Claims 1-16 are obvious over Desai in view of Kadima and Liversidge under §103.

• 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: This combination reinforces the obviousness of selecting a 9:1 ratio. Petitioner asserted that both Kadima and Liversidge teach ranges of albumin-to-paclitaxel ratios that encompass the claimed range. Kadima discloses ratios from about 0.5:1 to 10:1, and Liversidge discloses ratios from 0.01:9.99 to 9:1. Both of these prior art ranges entirely encompass the ’536 patent’s claimed range of about 1:1 to 9:1, which Petitioner argued makes a "compelling" prima facie case of obviousness.
  • Motivation to Combine: Kadima provides a strong, independent motivation to lower the albumin-paclitaxel ratio: cost reduction. Kadima explicitly identifies albumin as an "expensive ingredient" and a "cost-limiting component," teaching that reducing its use can make formulations more commercially feasible. A POSITA would combine this cost-saving motivation from Kadima with Desai's nanoparticle formulation to optimize the composition for both clinical efficacy and economic viability.
  • Expectation of Success: All three references operate in the same technical field of nanoparticle drug delivery. A POSITA would have been able to apply the ratio optimization principles taught by Kadima and Liversidge to the stable nanoparticle platform of Desai with a reasonable expectation of success.

4. Key Claim Construction Positions

• "the weight ratio of albumin to paclitaxel in the composition": Petitioner proposed that the broadest reasonable interpretation of this term includes the ratio of the starting ingredients used to make the composition, not only the ratio in the final, manufactured product. This construction is based on examples in the ’536 patent that calculate the ratio from the initial amounts of ingredients.
• "a particle size of less than about 200 nm": Petitioner proposed this term includes particle sizes of 220 nm or less. This construction is based on a generally understood 10% tolerance for the word "about" in the context of particle size measurements and is consistent with examples in the ’536 patent that report particle sizes up to 220 nm.

5. Key Technical Contentions (Beyond Claim Construction)

• Rebuttal of Secondary Considerations: Petitioner preemptively addressed the "unexpected results" that the Patent Owner relied upon during prosecution to overcome obviousness rejections. Petitioner contended these results were flawed and lacked a nexus to the claims for two primary reasons:
  • The "cell-binding" data was generated using a fluorescein-paclitaxel conjugate ("Flutax"), not paclitaxel, and the data points tested were outside the claimed "about 9:1" ratio.
  • The clinical data compared the 9:1 formulation to an "old" 19:1 formulation, which is not the closest prior art. The closest prior art disclosed in Desai includes formulations with ratios of 13.3:1 and 9.8:1, which were not used for comparison.

6. Relief Requested

• Petitioner requests institution of inter partes review and cancellation of claims 1-16 of the ’536 patent as unpatentable.