PTAB

IPR2018-00152

Apotex Inc v. Abraxis Bioscience LLC

Key Events

Petition

petition

Title: Compositions and Methods of Delivery of Pharmacological Agents
Brief Description: The ’788 patent describes pharmaceutical compositions for injection comprising nanoparticles of paclitaxel (an anticancer drug) and albumin (a carrier protein). The invention is particularly directed to formulations where the weight ratio of albumin to paclitaxel is about 1:1 to about 9:1.

Prior Art Relied Upon: Desai (WO 1999/000113).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner argued that Desai, an international patent application co-authored by inventors of the ’788 patent, discloses every limitation of the challenged claims. Specifically, Example 1 of Desai describes a process of combining 30 mg of paclitaxel with 270 mg of human serum albumin, which necessarily results in a composition with an albumin-to-paclitaxel weight ratio of exactly 9:1. Desai also explicitly teaches that this process produces nanoparticles with a typical diameter of 160-220 nm, which falls within the claimed "less than about 200 nm" limitation. Further, Desai teaches that the resulting lyophilized powder is for intravenous administration to treat diseases including cancer, arthritis, and restenosis, thereby anticipating the method claims (4-9) as well.
- Key Aspects: The core of the anticipation argument rested on the inherent disclosure of the 9:1 ratio from the specific amounts of starting ingredients listed in Desai's Example 1.

Prior Art Relied Upon: Desai (WO 1999/000113).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner asserted that even if Desai did not anticipate the claims, it rendered them obvious. Desai discloses a preferred embodiment, Capxol™, with an albumin-to-paclitaxel ratio of 13.3:1. Desai also discloses a range of other ratios, including the 9:1 ratio in Example 1 and a 9.8:1 ratio in Example 4. This establishes that the claimed 9:1 ratio falls within a range disclosed in the prior art, creating a prima facie case of obviousness.
- Motivation to Combine: A POSITA would be motivated to reduce the 13.3:1 ratio of Capxol™ to achieve the claimed ratio of about 9:1. Desai explicitly teaches developing formulations with higher paclitaxel concentrations to reduce infusion times and patient discomfort. This is achieved by increasing the drug loading relative to the albumin, which means lowering the albumin-to-paclitaxel ratio.
- Expectation of Success: A POSITA would have a reasonable expectation of success. Desai's own examples demonstrate stable formulations with ratios lower than 13.3:1 (e.g., 9:1 and 9.8:1). Furthermore, Desai describes Capxol™ as having exceptional stability, suggesting that a modest reduction in the amount of the albumin stabilizer would not cause problematic instability, especially when the goal is to optimize a known formulation.

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 of references reinforces the obviousness of the claimed 9:1 ratio. Kadima teaches albumin-paclitaxel formulations with ratios from 0.5:1 to 10:1. Liversidge, which relates to surface-modified nanoparticles, discloses and claims weight percentages that correspond to an albumin-paclitaxel ratio range of 0.01:9.99 to 9:1. Both of these prior art ranges entirely encompass the claimed range of about 1:1 to 9:1, making the claimed range prima facie obvious.
- Motivation to Combine: Kadima provides a compelling, independent motivation to lower the albumin-to-paclitaxel ratio: cost reduction. Kadima explicitly identifies albumin as an expensive, "cost-limiting component" and teaches using a lower ratio of albumin to paclitaxel to create more commercially feasible and inexpensive formulations. A POSITA would apply this clear cost-saving rationale to optimize Desai's nanoparticle formulation.
- Expectation of Success: The overlapping ranges taught by all three references, combined with Liversidge's teaching that such nanoparticle formulations can be optimized via routine screening, provided a strong expectation of success.

"the weight ratio of albumin to paclitaxel...": Petitioner argued this term should be interpreted to include the ratio of the starting ingredients used to create the composition, not just the ratio in the final, finished product. This construction is supported by examples in the ’788 patent itself, where the ratio is calculated from the initial amounts of albumin and paclitaxel mixed together. This interpretation is critical to the anticipation argument, as Desai's Example 1 describes the starting ingredients.
"a particle size of less than about 200 nm": Petitioner contended that the term "about" in the context of particle size allows for a variation of approximately 10%. This means the claim covers particle sizes up to 220 nm. This construction allows Desai's disclosed particle size range of 160-220 nm to meet the claim limitation.

Nexus for Secondary Considerations: Petitioner argued that the Patent Owner’s evidence of "unexpected results" from prosecution lacks the required nexus to the claimed invention. The crucial "cell-binding" experiments submitted by the inventor did not test the claimed combination of albumin and paclitaxel. Instead, they tested albumin with a fluorescein-paclitaxel conjugate (Flutax®), a different molecule with different binding properties. Petitioner contended that any results would be attributable to the fluorescein component, not the specific 9:1 ratio of albumin to paclitaxel, thus failing to support non-obviousness of the actual claims.

Petitioner requests institution of an inter partes review (IPR) and cancellation of claims 1-12 of the ’788 patent as unpatentable under 35 U.S.C. §102 and §103.