PTAB

IPR2017-00028

Laboratoire FrancAIS Du FractIONneMent Et des BIoTechnologies SA v. Novo Nordisk Healthcare AG

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Key Events
Petition

1. Case Identification

2. Patent Overview

  • Title: Virus Filtration of Liquid Factor VII Compositions
  • Brief Description: The ’762 patent discloses methods for removing viruses from liquid compositions of recombinant Factor VII (rFVII). The methods involve subjecting a solution containing a specific concentration of mostly activated Factor VII (FVIIa) to nanofiltration using a filter with a defined pore size.

3. Grounds for Unpatentability

Ground 1: Obviousness over Tomokiyo, Hill, and Burnouf - Claims 1-2, 4-6, and 10-15 are obvious over Tomokiyo, Hill, and Burnouf.

  • Prior Art Relied Upon: Tomokiyo (a 2003 journal article), Hill (a 2003 journal article), and Burnouf (a 2003 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Tomokiyo disclosed a method of removing viruses from a plasma-derived FVII composition having a concentration of 0.2 mg/mL and using a nanofilter with a 15 nm pore size, meeting several key claim limitations. However, Tomokiyo activated the FVII after filtration and used plasma-derived FVII, not recombinant FVII as claimed.
    • Motivation to Combine: A POSITA would combine the references for two main reasons. First, Hill taught that recombinant products present a solution to the serious risk of viral infections from plasma-derived products, motivating a POSITA to substitute Tomokiyo’s plasma-derived FVII with recombinant FVII. Second, Burnouf taught that nanofiltration "can essentially be used at various steps" but is typically "carried out at the end of the production process" to minimize recontamination. This would motivate a POSITA to reverse the order of Tomokiyo’s process by activating the FVII before the final nanofiltration step.
    • Expectation of Success: A POSITA would have a reasonable expectation of success in using rFVII instead of plasma FVII, as the physical properties relevant to nanofiltration were known to be substantially the same.

Ground 2: Obviousness over Tolo - Claims 1-2, 4-7, and 12-15 are obvious over Tolo.

  • Prior Art Relied Upon: Tolo (WO 1999/064441).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner contended that Tolo disclosed a method for removing viruses from various therapeutic proteins, explicitly including activated Factor VII (FVIIa), using nanofiltration. Tolo taught using a nanofilter with a pore size of 10-40 nm and compositions where 100% of the FVII polypeptides are in the activated form. Although Tolo’s specific example used IFN-α at a lower concentration (0.04 mg/mL), Petitioner argued that Tolo’s broader disclosure rendered the claims obvious.
    • Motivation to Combine: A POSITA would be motivated to apply Tolo's generally disclosed method to rFVIIa, as Tolo expressly identified it as a suitable protein. Further, a POSITA would have been motivated to increase the protein concentration to achieve commercially viable throughput, a routine optimization in the art.
    • Expectation of Success: Because Tolo’s method was described as applicable to coagulation factors generally, a POSITA would have had a high expectation of success.

Ground 3: Obviousness over Eibl '023 and Mollerup - Claims 1-2, 4, 6, and 11-15 are obvious over Eibl '023 and Mollerup.

  • Prior Art Relied Upon: Eibl '023 (WO 2004/011023) and Mollerup (a 1995 journal article).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground is contingent on the '762 patent losing its 2003 priority date, making Eibl '023 (published Feb. 2004) prior art. Petitioner asserted that Eibl '023 disclosed a method for removing viruses from a recombinant FVIIa composition using a nanofilter with a pore size of 80 nm or less, with 100% of the FVII in activated form. Eibl '023 thus allegedly met all limitations of claim 1 except for the concentration range of 0.01-5 mg/mL, instead disclosing a much lower concentration of 20 ng/mL.
    • Motivation to Combine: Mollerup disclosed purifying rFVIIa solutions at much higher concentrations (0.8 mg/mL and 1.4 mg/mL), which fall within the claimed range, and explicitly advised that concentration must be "carefully control[led]." A POSITA would combine Eibl '023's method with Mollerup's teachings on concentration to increase the rate of purification and improve throughput for commercial production.
    • Expectation of Success: Mollerup provided a clear expectation of success by teaching that even at these higher concentrations, the "autolytic reaction rate of rFVIIa in this system is low."

  • Additional Grounds: Petitioner asserted additional obviousness challenges based on combinations including Pedersen, Hill, and Burnouf to address specific dependent claims related to pH ranges, cell culture conditions, and filter materials.

4. Key Claim Construction Positions

  • Petitioner’s argument for several grounds relied on a loss of priority date, which hinged on the construction of the term "Factor VII polypeptide."
  • Petitioner argued that under the broadest reasonable interpretation, the term must be construed according to the patent’s explicit definition, which includes not only Factor VII and FVIIa but also "derivatives and Factor VII conjugates" (e.g., PEGylated FVII).
  • Petitioner contended this broad definition constituted new matter added in the 2004 PCT application that was not supported by the written description of the 2003 priority documents. Consequently, Petitioner argued claims 1-15 are not entitled to the 2003 priority date, making their effective filing date December 1, 2004, and rendering intervening publications like Eibl '023 available as prior art.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under § 325(d) would be inappropriate because the petition presented prior art and arguments in a new light.
  • It was argued that the asserted combinations were not previously considered by the USPTO. Specifically, Eibl '023 was not cited against the claims during prosecution, and while other references (e.g., Hill, Tomokiyo) were of record, they were either presented only in an Information Disclosure Statement or combined differently by the Examiner, without the benefit of the expert testimony provided in the petition.

6. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-15 of Patent 9,102,762 as unpatentable.