PTAB

IPR2019-00582

Associated British Foods v. Cornell Research Foundation Inc

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petition

1. Case Identification

2. Patent Overview

  • Title: Overexpression of Phytase Genes in Yeast Systems
  • Brief Description: The ’572 patent describes methods for producing the enzyme phytase, which is used as an animal feed additive. The method involves providing an appA polynucleotide (gene) from Escherichia coli, expressing this gene in a Pichia yeast strain, and then isolating the resulting protein. A key feature of the claimed invention is that the phytase produced in yeast has increased thermostability compared to phytase expressed in a non-yeast host cell.

3. Grounds for Unpatentability

Ground 1: Claims 1-5, 9, and 10 are obvious over [Kretz](https://ai-lab.exparte.com/case/ptab/IPR2019-00582/doc/1003) in view of [Cheng](https://ai-lab.exparte.com/case/ptab/IPR2019-00582/doc/1004).

  • Prior Art Relied Upon: Kretz (Patent 5,876,997) and Cheng (Patent 5,985,605).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that Kretz taught all essential steps of the claimed method: providing a polynucleotide for an E. coli phytase, expressing it in yeast host cells, and isolating the resulting protein. Petitioner argued that the E. coli phytase disclosed in Kretz is an obvious variant of the claimed appA phytase. While Kretz taught using yeast generally, Cheng specifically disclosed expressing bacterial phytases in the yeast Pichia to achieve high yields and efficiency. Petitioner contended that the claimed "increased thermostability" is not an unexpected result but an inherent property that results from expressing a bacterial enzyme in a yeast host, which is capable of glycosylation.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine these references to improve an existing process. Kretz disclosed a desirable, heat-stable E. coli phytase suitable for animal feed. A POSITA seeking to produce this enzyme economically would have looked to Cheng, which taught that using Pichia yeast was a "well characterized" method for increasing the production efficiency and yield of bacterial phytases.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success because Kretz already established the feasibility of expressing E. coli phytase in yeast, and Cheng provided detailed methods for expressing other bacterial phytases in the specific Pichia host. The combination represented the application of a known, efficient production platform to a known, desirable enzyme.

Ground 2: Claims 1-5, 9, and 10 are obvious over [Greiner](https://ai-lab.exparte.com/case/ptab/IPR2019-00582/doc/1007), [Dassa](https://ai-lab.exparte.com/case/ptab/IPR2019-00582/doc/1006), and Cheng.

  • Prior Art Relied Upon: Greiner (a 1993 journal article), Dassa (a 1990 journal article), and Cheng (Patent 5,985,605).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground provided a more direct mapping to the claimed appA polynucleotide. Dassa disclosed the exact nucleotide sequence for the appA gene from E. coli. Greiner subsequently confirmed that the enzyme produced from Dassa's gene sequence functions as a phytase with high specificity and stability. As in Ground 1, Cheng supplied the missing element by teaching a method of expressing bacterial phytases in Pichia yeast. This combination disclosed all elements of the independent claims.
    • Motivation to Combine: A POSITA would combine these references to produce a known, valuable enzyme using an improved manufacturing process. Greiner identified the appA phytase as an attractive candidate for animal feed due to its stability. To produce this enzyme economically, a POSITA would have turned to Cheng's methods for expressing bacterial phytases in high-yield hosts like Pichia to increase efficiency and reduce costs.
    • Expectation of Success: Success would be reasonably expected because the combination involved expressing a specific, well-characterized phytase gene (from Dassa and Greiner) using a proven method for expressing similar bacterial enzymes (from Cheng) in an industrially recognized yeast host.

Ground 3: Claims 1-5, 9, and 10 are obvious over Greiner, Dassa, [Romanos](https://ai-lab.exparte.com/case/ptab/IPR2019-00582/doc/1017), and [Van Gorcom](https://ai-lab.exparte.com/case/ptab/IPR2019-00582/doc/1008).

  • Prior Art Relied Upon: Greiner, Dassa, Romanos (a 1995 journal article), and Van Gorcom (Patent 5,436,156).
  • Core Argument for this Ground:
    • Prior Art Mapping: Greiner and Dassa again provided the specific appA phytase and its encoding gene. This ground replaced Cheng with Romanos and Van Gorcom to teach the expression in yeast. Romanos identified Pichia as a "mainstream expression host" known for producing "extremely high yields" of proteins, including bacterial enzymes. Van Gorcom taught general, industrially viable methods for producing high levels of recombinant phytase in yeast hosts on an economical scale.
    • Motivation to Combine: The motivation was to leverage the superior properties of the appA phytase (from Greiner) by producing it in the most efficient host available. Romanos explicitly taught that Pichia achieved much higher yields than other yeasts, providing a clear motivation to select it as the host. Van Gorcom provided the established industrial context and methods for producing phytases in yeast economically.
    • Expectation of Success: A POSITA would have expected success because Romanos taught that Pichia was a suitable host for bacterial enzymes, and Van Gorcom taught that phytase genes exhibit a high degree of homology across different microbial species, making the substitution of one phytase for another in a yeast expression system predictable.
  • Additional Grounds: Petitioner asserted additional obviousness challenges for claims 1-5 (Grounds IV-VI) by adding the teachings of Olsen (a 1991 journal article) to each of the combinations in Grounds I-III. Olsen was cited for its explicit teaching that expressing bacterial enzymes in yeast (which glycosylates the protein) results in substantially higher thermostability compared to expression in bacterial cells, further supporting the obviousness of the thermostability limitation.

4. Key Claim Construction Positions

  • "appA polynucleotide": Petitioner argued that this term should be construed narrowly as "the gene originally defined as E. coli periplasmic phosphohydrolase gene... identified by GenBank accession number M58708," as explicitly referenced in the ’572 patent. Petitioner contended that its invalidity arguments prevail even under this narrower construction, which would necessarily prove unpatentability under any broader construction proposed by the Patent Owner.

5. Key Technical Contentions (Beyond Claim Construction)

  • Inherent Thermostability: A central technical argument repeated across multiple grounds was that the claimed "increased thermostability" is an inherent and expected result of post-translational modification (glycosylation) that occurs when expressing a bacterial protein in a eukaryotic host like yeast. Petitioner argued this was a known phenomenon in the art, not an inventive discovery, and therefore the limitation adds no patentable weight to the claims.

6. Arguments Regarding Discretionary Denial

  • Petitioner argued that the grounds presented are not cumulative of issues previously considered by the USPTO during prosecution. It asserted that the specific prior art combinations, particularly the combination of Kretz and Cheng, were never considered by the Examiner. Furthermore, Petitioner argued that the Examiner was never presented with key teachings, such as Olsen’s disclosure on the expected increase in thermostability or Greiner’s confirmation of the phytase activity of the appA enzyme, which directly address arguments made by the applicant to overcome prior rejections.

7. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-5, 9, and 10 of the ’572 patent as unpatentable.