Kashiv BioSciences, LLC v. Amgen Inc.

1. Case Identification

• Case #: IPR2019-00797
• Patent #: 9,643,997
• Filed: March 7, 2019
• Petitioner(s): Kashiv BioSciences, LLC
• Patent Owner(s): Amgen Inc.
• Challenged Claims: 9-10, 13-15, 17-21, 23, 26-30

2. Patent Overview

• Title: Capture Purification Processes for Proteins Expressed in a Non-mammalian System
• Brief Description: The ’997 patent relates to methods for purifying proteins that are expressed in non-mammalian systems and exist in a non-native, limited solubility form, such as inclusion bodies. The claimed process involves solubilizing the protein, forming a refold solution, applying that solution to a separation matrix, and then washing the matrix and eluting the purified protein.

3. Grounds for Unpatentability

Ground 1: Anticipation by Ferré - Claims 9-10, 13-14, 17-18, 20-21, 26, 29, and 30 are anticipated under 35 U.S.C. §102 by Ferré.

• Prior Art Relied Upon: Ferré (a 2005 article in Protein Science).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Ferré disclosed every element of the claimed method in a single, integrated process. Ferré described purifying human β2-microglobulin from E. coli inclusion bodies by first solubilizing them in 8M urea (a denaturant). It then formed a refold solution by diluting the solubilized protein with a buffer containing Tris-HCl (an aggregation suppressor and protein stabilizer). Critically, Ferré taught that the nascently folded protein was then “directly captured” by an expanded bed adsorption (EBA) column (a separation matrix), which was subsequently washed and eluted.
  • Key Aspects: Petitioner contended that Ferré's express teaching of "direct capture" after refolding inherently disclosed the step of applying the refold solution to a separation matrix without any intervening dilution, centrifugation, or dialysis steps, thereby anticipating the claims under any reasonable construction.

Ground 2: Obviousness over Komath - Claims 9-10, 13-14, 17-18, 20-21, 26, 29, and 30 are obvious under 35 U.S.C. §103 over Komath.

• Prior Art Relied Upon: Komath (WO 2004/001056).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Komath, which was presented as an anticipatory reference in an alternative ground, disclosed all steps of claim 9 for purifying recombinant G-CSF from E. coli inclusion bodies. The process included solubilizing with urea, refolding in a solution containing polysorbate 20 (a known aggregation suppressor), applying the refolded solution to an ion-exchange chromatography column, washing the column, and eluting the G-CSF.
  • Motivation to Combine: Petitioner argued that a Person of Ordinary Skill in the Art (POSA) would have been motivated to perform the steps disclosed by Komath in the claimed sequence because they represented the well-known, standard workflow for purifying proteins from inclusion bodies. Komath's stated goal of a "simple and cost effective process" with "fewer steps" would have motivated a POSA to use the disclosed steps together to achieve higher throughput and economy.
  • Expectation of Success: A POSA would have had a reasonable expectation of success. Komath used standard components (e.g., urea, non-ionic detergents) and conventional ion-exchange chromatography (IEX) principles that were well-understood in the art. The fact that Komath reported its own process was "optimized for maximum recovery" would have further confirmed to a POSA that the combination would be successful.

Ground 3: Obviousness over Ferré, Komath, or Dietrich in view of Rosendahl - Claims 15, 19, 23, 27, and 28 are obvious.

• Prior Art Relied Upon: Ferré, Komath, or Dietrich in combination with Rosendahl (Application # 2004/0018586).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground targeted dependent claims requiring specific chemical components: a reductant (e.g., DTT, glutathione) in the solubilization solution (claims 15, 23) and a redox component (e.g., a glutathione-reduced/oxidized pair) in the refold buffer (claims 19, 27, 28). Petitioner argued that while the primary references (Ferré, Komath, Dietrich) taught the basic process of claim 9, Rosendahl taught the specific components needed to satisfy these dependent claims.
  • Motivation to Combine: Rosendahl was directed to methods for refolding proteins with disulfide bonds and expressly taught using the claimed reductants and redox components to ensure proper refolding and achieve high yields. Petitioner argued a POSA seeking to purify proteins like those described in the primary references (which have disulfide bonds) would have been motivated to incorporate Rosendahl's "useful" and "preferred" components into the general purification frameworks of Ferré, Komath, or Dietrich to improve efficiency and yield.
  • Expectation of Success: A POSA would reasonably expect success because Rosendahl's components were specifically designed to solve the known problem of ensuring correct disulfide bond formation during refolding, a critical step for achieving a biologically active protein.

• Additional Grounds: Petitioner asserted additional anticipation challenges based on Hahm (a 2001 journal article) and Dietrich (Application # 2008/0260684). These references were alleged to disclose similar multi-step protein purification processes from inclusion bodies using affinity chromatography and ion-exchange chromatography, respectively.

4. Key Claim Construction Positions

• Petitioner dedicated significant argument to the construction of "applying the refold solution to a separation matrix."
• Petitioner argued this term should be given its plain and ordinary meaning, which would encompass both direct application and application with intermediate steps (e.g., filtration, pH adjustment). This position was based on the specification's examples and the prosecution history, where the Patent Owner distinguished prior art but did not amend the claim to the more restrictive "directly applying" language used in a parent patent. Petitioner asserted the claims were unpatentable even under the narrower construction ("without intervening steps of dilution, centrifugation, dialysis, or precipitation") that Patent Owner had advanced in a separate litigation.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be inappropriate. The basis for this argument was that the specific prior art references and the detailed unpatentability arguments presented in the petition were not previously considered by the Examiner during the original prosecution of the ’997 patent.

6. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 9-10, 13-15, 17-21, 23, and 26-30 of the ’997 patent as unpatentable.