PTAB

IPR2017-01599

Nuevolution AS v. Chemgene Holding ApS

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1. Case Identification

2. Patent Overview

  • Title: DNA-Encoded Chemical Library Synthesis
  • Brief Description: The ’381 patent relates to methods for synthesizing and screening large chemical libraries. The invention combines a "split-and-mix" synthesis stage to create diverse "bi-functional carrier molecules" with a subsequent "templated synthesis" stage where these carriers react in a template-directed manner.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1, 3, 5, 6, 10-15, 17, 24, 25, 26, 31, 34, 37, 44 under §102 over [WO ’825](https://ai-lab.exparte.com/case/ptab/IPR2017-01599/doc/1003)

  • Prior Art Relied Upon: Freskgård (WO 2004/039825) ("WO ’825").
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that WO ’825 explicitly teaches combining its "Mode 2" (split-and-mix synthesis) with its "Mode 1" (one-pot templated synthesis). WO ’825’s Mode 2 was asserted to disclose the carrier synthesis steps of the independent claims (claims 1(a)-(g) and 5(a)-(g)), including preparing bi-functional molecules in separate wells, combining them into an admixture, and optionally repeating the synthesis. WO ’825’s Mode 1 was argued to teach the final templated reaction step (claims 1(h) and 5(h)), wherein the admixture of carriers is contacted with templates that facilitate a reaction. Petitioner contended that WO ’825’s disclosure of template "assembly platforms" with "unique anti-codon regions" that are "sequence specific" meets the "region limitation" of claim 1, which requires the identifier region that hybridizes to the template to be the same region that identifies the molecule fragment.
    • Key Aspects: Petitioner asserted that the combination of Mode 2 and Mode 1 in WO ’825's Example 7 directly anticipates claim 5, which lacks the "region limitation" added to claim 1 during prosecution.

Ground 2: Obviousness of Claims 1, 3, 5, 6, 10-15, 17, 24, 25, 26, 31, 34, 37, 44 over WO ’825 in view of [WO ’008](https://ai-lab.exparte.com/case/ptab/IPR2017-01599/doc/1004)

  • Prior Art Relied Upon: WO ’825 and Pedersen (WO 02/103008) ("WO ’008").
  • Core Argument for this Ground:
    • Prior Art Mapping: WO ’825 teaches split-and-mix synthesis (Mode 2) to prepare repertoires of carrier molecules. WO ’008 teaches a one-pot template-encoded synthesis method where bi-functional carriers ("building blocks") hybridize to templates having coding elements, allowing molecule fragments ("functional entities") to react. Petitioner argued that the ’381 patent itself admits that the techniques of WO ’008 can be applied to templated-encoded synthesis.
    • Motivation to Combine: A POSITA would combine these references because WO ’825 explicitly promotes using carriers made via its split-and-mix strategy in a subsequent one-pot synthesis to gain the benefits of both approaches: library diversity from split-and-mix and reaction efficiency from templated synthesis. A POSITA would have been motivated to substitute the known carriers from WO ’825 into the known template-encoded synthesis system of WO ’008.
    • Expectation of Success: Because the carrier molecules disclosed in WO ’825 and WO ’008 are structurally similar and used for the same purpose, a POSITA would have a reasonable expectation of success in using WO ’825 carriers in the WO ’008 system to produce large, predictable libraries of template-encoded products.

Ground 3: Anticipation of Claims 1, 5, 23, 24, 26, 31, 45 under §102 over [WO ’427](https://ai-lab.exparte.com/case/ptab/IPR2017-01599/doc/1016)

  • Prior Art Relied Upon: Franch (WO 2004/083427) ("WO ’427").

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner argued WO ’427, which the ’381 patent specification incorporates for its templated synthesis methods, anticipates the claims. WO ’427 was asserted to teach synthesizing bi-functional carriers ("building blocks") in separate wells, each comprising a molecule fragment and an oligonucleotide identifier ("anti-codon"). These carriers are then combined into "pools" (admixtures) and contacted with templates. In the method of WO '427's Figure 1, carriers are sequentially hybridized to a template and their identifiers are ligated together (e.g., to a hairpin on the template and then to each other) prior to the reaction of the molecule fragments. This process of carrier synthesis, admixing, and subsequent contacting with a template for a codon-specific reaction was argued to meet all limitations of independent claims 1 and 5.
    • Key Aspects: The argument centered on WO ’427's disclosure of ligating carrier identifiers to each other on the template before the chemical reaction, which directly maps to the claimed method.

  • Additional Grounds: Petitioner asserted additional obviousness challenges, including obviousness over WO ’825 alone; a combination of WO ’825 and WO ’929; obviousness over WO ’427 alone; and a combination of WO ’825 and WO ’427. These grounds relied on similar arguments regarding the combination of known split-and-mix carrier synthesis with known templated reaction methods.

4. Key Claim Construction Positions

  • "Template": Petitioner argued that the term "template," while not expressly defined, is used in the specification exclusively in the context of "templated synthesis." Based on the specification and prosecution history admissions, Petitioner proposed that a POSA would understand "template" to mean "an entity capable of binding carrier molecule(s) to bring molecule fragment(s) into reactive proximity with another reactive group." This construction was crucial because it confirmed that entities described in the prior art, such as the "assembly platforms" of WO ’825, qualify as templates under the claims.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1, 3, 5, 6, 10-15, 17, 23-26, 31, 34, 37, 44, and 45 of Patent 8,168,381 as unpatentable.