Nuevolution AS v. Chemgene Holding ApS

1. Case Identification

• Case #: IPR2017-01603
• Patent #: 8,951,728
• Filed: June 14, 2017
• Petitioner(s): Nuevolution A/S
• Patent Owner(s): Chemgene Holding APS
• Challenged Claims: 1

2. Patent Overview

• Title: DNA-Encoded Synthesis Methods
• Brief Description: The ’728 patent relates to methods for preparing and screening DNA-encoded chemical libraries. The invention purports to be an advantageous combination of two established techniques: "split-and-mix" synthesis (Stage 1) to create diverse "carrier" molecules and "templated" synthesis (Stage 2) to generate encoded chemical libraries for biological screening.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claim 1 over WO '008

• Prior Art Relied Upon: Pedersen et al. (WO 02/103008) ("WO '008'").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that WO '008, which discloses methods for synthesizing DNA-encoded libraries from "building blocks," anticipates every limitation of claim 1. WO '008 allegedly teaches preparing bi-functional carrier molecules (its "building blocks") in separate reaction wells, where molecule fragments ("functional entities") are attached to oligonucleotide identifiers ("complementing elements") via a linker. The petition asserted that WO '008's Example 108 details preparing twelve different carriers in different wells, satisfying the carrier synthesis steps. These carriers are then combined into an admixture and contacted with templates that have specific coding regions, causing the carriers to hybridize in a codon-specific manner. This hybridization, which brings the molecule fragments into reactive proximity, allegedly meets the final "template hybridization" and "region limitation" clauses of claim 1.

Ground 2: Anticipation of Claim 1 over WO '825

• Prior Art Relied Upon: Freskgård et al. (WO 2004/039825) ("WO '825'").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that WO '825 discloses library synthesis using two distinct modes that can be combined: Mode 2 (split-and-mix synthesis) and Mode 1 (one-pot templated synthesis). The petition asserted that WO '825's Mode 2, detailed in its Examples 7 and 9, teaches preparing different carrier molecules in separate wells by attaching molecule fragments and oligonucleotide identifiers to a linker molecule. These carriers are then combined to form "repertoires" (admixtures), satisfying the initial steps of claim 1. This repertoire is then used as an intermediate library for a Mode 1 templated synthesis. Petitioner contended that WO '825's "assembly platform" method employs templates with unique anti-codon regions that specifically hybridize to the unique codon regions of the carriers, bringing the molecule fragments into close proximity for reaction. This process was argued to meet the template hybridization and region identification limitations of claim 1, thereby anticipating the entire claim.

Ground 3: Obviousness of Claim 1 over WO '008 in view of WO '825

• Prior Art Relied Upon: WO '008 (WO 02/103008) and WO '825 (WO 2004/039825).

• Core Argument for this Ground:

  • Prior Art Mapping: Petitioner argued that even if not anticipated, claim 1 is obvious over the combination of WO '008 and WO '825. WO '008 discloses a complete system for template-encoded synthesis, while WO '825 teaches various methods for preparing repertoires of bi-functional carriers using split-and-mix techniques (Mode 2). The core argument was that it would have been obvious to a person of ordinary skill in the art (POSITA) to substitute the carriers prepared by the split-and-mix methods of WO '825 into the template-encoded synthesis system of WO '008.
  • Motivation to Combine: A POSITA would combine the references to leverage the benefits of each known technique. WO '825's split-and-mix carrier synthesis offered improved reaction versatility and the ability to create large, diverse intermediate libraries. Applying these carrier libraries to WO '008's one-pot, template-encoded synthesis would be a predictable and advantageous strategy to generate even larger and more diverse final libraries of templated products.
  • Expectation of Success: A POSITA would have had a high expectation of success because the combination involved substituting one known type of DNA-tagged carrier (from WO '825) for another (from WO '008) within a well-understood template hybridization system. Both references taught using such carriers for the same purpose—to bring molecule fragments into reactive proximity via template hybridization.

• Additional Grounds: Petitioner asserted numerous additional anticipation and obviousness challenges against claim 1 based on WO ’627, WO ’994, WO ’929, and WO ’427, as well as further combinations thereof, relying on similar arguments that these references taught all required steps of carrier synthesis, combining, and template-encoded hybridization.

4. Key Claim Construction Positions

• "Template": Petitioner argued that while not expressly defined, the term "template" as used in the ’728 patent requires a specific function beyond simple binding. Based on the specification and prosecution history, Petitioner contended a POSITA would understand a "template" to be "an entity capable of binding carrier molecule(s) to bring molecule fragment(s) into reactive proximity with another reactive group." This construction was central to arguing that prior art references disclosing nucleic acid strands that direct chemical reactions met this limitation.

5. Relief Requested

• Petitioner requests the institution of an inter partes review and the cancellation of claim 1 of Patent 8,951,728 as unpatentable.