Wuhan Healthgen Biotechnology Corp Of Wuhan China v. Ventria Bioscience Inc

1. Case Identification

• Case #: IPR2022-00407
• Patent #: 8,609,416
• Filed: January 7, 2022
• Petitioner(s): Wuhan Healthgen Biotechnology Corp.
• Patent Owner(s): Ventria Bioscience Inc.
• Challenged Claims: 1, 2, 11-25

2. Patent Overview

• Title: Methods and Compositions Comprising Heat Shock Proteins
• Brief Description: The ’416 patent discloses cell culture media supplements produced in a plant. The supplement contains a protein cell culture component, such as recombinant human serum albumin (rHSA), which is co-purified with at least 0.01% wt/wt of a heat shock protein and has less than 1 EU/mg of endotoxin.

3. Grounds for Unpatentability

Ground 1: Obviousness over Deeter and Van Urk - Claims 1, 2, 11-19, 21, 23, and 25 are obvious over Deeter in view of Van Urk.

• Prior Art Relied Upon: Deeter (WO 2007/002762A2) and Van Urk (WO 00/44772).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Deeter disclosed all elements of independent claim 1 except for the low endotoxin level. Deeter taught a plant-derived rHSA supplement (marketed as Cellastim) for use in cell culture media that improved cell growth and productivity. Petitioner contended that Deeter’s rHSA product inherently contained at least 0.01% wt/wt of co-purifying heat shock proteins because the disclosed purification process (e.g., using Q-Sepharose chromatography) would not have separated them from rHSA due to their similar biochemical properties. However, Deeter’s product contained disadvantageously high levels of endotoxin. To remedy this deficiency, Petitioner asserted that a person of ordinary skill in the art (POSA) would look to Van Urk, which taught specific processes for purifying rHSA, including plant-derived rHSA, to achieve a product that is essentially free of endotoxin.
  • Motivation to Combine: A POSA would combine Deeter with Van Urk to improve Deeter’s promising cell culture supplement. Endotoxin was a well-known contaminant detrimental to cell culture, and a POSA would be motivated to remove it from Deeter's high-yield, plant-derived rHSA to enhance its performance and safety, using the established purification methods taught by Van Urk.
  • Expectation of Success: A POSA would have a reasonable expectation of success because Van Urk’s endotoxin removal techniques were applicable to albumin from various sources, including plants. Critically, Petitioner argued that while a POSA would expect to successfully remove endotoxin, they would not expect Van Urk's purification process to remove the tightly bound, co-purifying heat shock proteins. This is because the methods in Van Urk (e.g., ion exchange chromatography) were not designed for and were not capable of separating proteins with such similar properties as rHSA and heat shock proteins.

Ground 2: Obviousness over Deeter and Matejtschuk - Claims 1, 2, 11-19, 21, 23, and 25 are obvious over Deeter in view of Matejtschuk.

• Prior Art Relied Upon: Deeter (WO 2007/002762A2) and Matejtschuk (a 2000 journal article).

• Core Argument for this Ground:

  • Prior Art Mapping: The argument mirrored Ground 1, with Matejtschuk substituting for Van Urk as the source for endotoxin removal technology. Petitioner asserted Deeter taught a plant-derived rHSA supplement inherently containing heat shock proteins but with high levels of endotoxin. Matejtschuk, a review article, explicitly taught that an "ideal" albumin product should be free from contaminants like endotoxins. It disclosed that applying an albumin solution to a single anion-exchange chromatography column (DEAE-Sepharose) consistently and significantly lowered endotoxin concentrations to acceptable levels (less than 1 EU/mL).
  • Motivation to Combine: The motivation was identical to that in Ground 1: a POSA would be motivated to purify the high-endotoxin rHSA from Deeter to improve its function as a cell culture supplement. A POSA would naturally look to a reference like Matejtschuk, which directly addressed the known problem of endotoxin contamination in albumin solutions and provided a straightforward, effective solution.
  • Expectation of Success: A POSA would reasonably expect that applying the well-established DEAE-Sepharose chromatography technique from Matejtschuk to Deeter’s rHSA would successfully reduce endotoxin levels. As with the Van Urk combination, Petitioner argued that a POSA would not have expected this standard anion-exchange process to separate the heat shock proteins from the rHSA, thus arriving at the claimed composition.

• Additional Grounds: Petitioner asserted additional obviousness challenges (Grounds 2 and 4) against dependent claims 15, 20, 22, and 24 by adding the InVitria Press Releases to the Deeter/Van Urk and Deeter/Matejtschuk combinations. The press releases were argued to explicitly disclose the use of Deeter’s Cellastim product for enhancing the growth and productivity of the specific cell types recited in the dependent claims (e.g., primary cells, stem cells, CHO cells, and Vero cells).

4. Key Claim Construction Positions

• "cell culture medium supplement composition" (preamble, claim 1): Petitioner argued this preamble term is limiting because it provides antecedent basis for "the composition" in the body of the claim.
• "produced in a plant" (claim 1): Petitioner argued this term should be construed according to its express definition in the ’416 patent’s specification: "been obtained directly or indirectly from a plant cell."
• "heat shock protein" (claim 1): Petitioner asserted this term should be construed according to its definition in the specification as a "naturally occurring or synthetic form of a member of the heat shock protein super family that retains anti-apoptotic activity."

5. Key Technical Contentions (Beyond Claim Construction)

• Inherency of Heat Shock Proteins in Deeter: The central technical pillar of the petition was the argument that Deeter's prior art rHSA product (Cellastim) inherently contained the claimed levels of heat shock protein. Petitioner supported this by comparing the rHSA purification processes described in Deeter and the ’416 patent, arguing their similarity meant Deeter’s process would not have removed the naturally co-purifying heat shock proteins. Petitioner further argued that the ’416 patent itself effectively acknowledges this by framing the invention as a "discovery" that heat shock proteins co-purified with rHSA, rather than an invention of a new composition.

6. Arguments Regarding Discretionary Denial

• Petitioner argued against discretionary denial under 35 U.S.C. §325(d), asserting that the primary prior art combinations were not previously before the USPTO. While Deeter was submitted in an Information Disclosure Statement, it was never discussed on the record or used in any rejection. Furthermore, the key secondary references teaching endotoxin removal (Van Urk and Matejtschuk) and the InVitria Press Releases were never submitted to or considered by the Examiner during prosecution.

7. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1, 2, and 11-25 of the ’416 patent as unpatentable.