Wuhan Healthgen Biotechnology Corp v. Ventria Bioscience Inc

1. Case Identification

• Case #: IPR2023-00684
• Patent #: 11,492,389
• Filed: March 31, 2023
• Petitioner(s): Wuhan Healthgen Biotechnology Corp.
• Patent Owner(s): Ventria Bioscience Inc.
• Challenged Claims: 1-29

2. Patent Overview

• Title: Cell Culture Media Compositions Comprising Plant-Derived Recombinant Albumin
• Brief Description: The ’389 patent relates to cell culture media compositions that include recombinant human serum albumin (rHSA) produced in a transgenic plant, such as rice. The compositions are characterized by high purity, specifically requiring low levels of endotoxin (< 1 EU/mg) and, for certain claims, low levels of residual detergent (< 10 ppm).

3. Grounds for Unpatentability

Ground 1: Obviousness over Hatsuyama, Deeter, and General Knowledge

• Claims 1-29 are obvious over Hatsuyama in view of Deeter and a POSA’s general knowledge.
  • Prior Art Relied Upon: Hatsuyama (Application # 2007/0166825), Deeter (WO 2007/002762), and a Person of Ordinary Skill in the Art’s (POSA) General Knowledge regarding acceptable detergent levels in purified proteins, as exemplified by references including Van Holten (Application # 2006/0110399) and Bonomo (Patent 5,094,960).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued the claimed invention is an obvious combination of known elements. Hatsuyama taught a serum-free cell culture medium containing highly purified rHSA suitable for pharmaceutical use, with an endotoxin level far below the claimed limit (0.002 EU/mg). While Hatsuyama exemplified rHSA from yeast, it expressly taught that the rHSA could be obtained from any recombinant host, including transgenic plants. Deeter taught a high-yield, cost-effective method for producing rHSA in transgenic rice and demonstrated its successful use in cell culture. Petitioner asserted a POSA would combine these teachings by substituting Deeter's rice-derived rHSA for the yeast-derived rHSA in Hatsuyama's cell culture medium.
    • To meet the purity limitations of the independent claims, Petitioner argued a POSA would have employed routine and well-known purification techniques.
      • Endotoxin Limitation (< 1 EU/mg): A POSA would be motivated to purify the plant-derived rHSA to the high standard taught by Hatsuyama. Petitioner contended that known techniques, such as two-phase separation using the detergent Triton X-114, were proven effective for removing endotoxins from similar proteins (e.g., bovine serum albumin, or BSA) and would have been expected to work for Deeter's rHSA.
      • Detergent Limitation (< 10 ppm): If a detergent-based method was used for endotoxin removal, a POSA would have known it was imperative to remove the detergent for cell culture applications. Petitioner cited general knowledge in the art that detergents are cytotoxic and must be reduced to levels below 10 ppm, with well-known techniques like hydrophobic interaction chromatography (HIC) available and effective for this purpose.
      • Plant Component Limitation (Claim 24): This claim requires a plant carbohydrate or lipid. Petitioner argued a POSA would have reasonably expected Deeter's rice-derived rHSA to retain bound plant lipids, as lipids are known to stabilize albumin and enhance its function in cell culture.
    • Motivation to Combine (for §103 grounds): Petitioner asserted several motivations. First, both Hatsuyama and Deeter sought to solve the same problem: avoiding the risk of contamination from animal-associated pathogens by using recombinant proteins in cell culture media. Second, Hatsuyama explicitly suggested using plant-derived rHSA, providing a direct suggestion to look for such a source. Third, Deeter's high-yield transgenic rice system represented a predictable and economically advantageous alternative to the yeast system exemplified in Hatsuyama, providing a strong motivation for its adoption.
    • Expectation of Success (for §103 grounds): A POSA would have a reasonable expectation of success in making the substitution and subsequent purification. Hatsuyama’s teaching that rHSA from any host was suitable, combined with Deeter’s successful use of rice-derived rHSA in culture, rendered the combination predictable. Furthermore, the purification techniques for removing endotoxins and detergents were standard procedures known to be effective for albumins, which share highly similar physicochemical properties regardless of their source.

4. Key Claim Construction Positions

• Petitioner argued that the preamble phrases in the independent claims, such as "improving the growth, viability, and/or productivity of cultured cells," are not limiting. It contended these phrases do not provide antecedent basis for any claim terms and were not relied upon to establish patentability during prosecution.
• Petitioner proposed that the term "recombinant human albumin" should be construed to include not only the native sequence but also variants, derivatives, and fragments that retain the biological or therapeutic activity of native albumin. This construction was argued to be consistent with the patent's specification and necessary to encompass preferred embodiments.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. § 325(d) would be inappropriate because the prior art and arguments presented in the petition were not cumulatively considered during prosecution. Specifically, Petitioner asserted that the primary reference, Hatsuyama, which teaches cell culture media with highly purified rHSA, was never cited or considered by the Examiner.
• Additionally, Petitioner argued that the Examiner made material errors when previously evaluating Deeter. These alleged errors included erroneously concluding that (1) the need to control endotoxin levels was not appreciated at the time of Deeter's invention, and (2) Deeter's rHSA was "incapable" of being purified to the claimed endotoxin levels, contrary to what a POSA would have understood from well-known purification techniques.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-29 of Patent 11,492,389 as unpatentable.