PTAB

IPR2017-01598

Nuevolution A/S v. Chemgene Holding ApS

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1. Case Identification

2. Patent Overview

  • Title: DNA-encoded synthesis methods for preparing and screening chemical libraries.
  • Brief Description: The ’381 patent relates to methods for synthesizing diverse chemical libraries encoded by DNA tags. The claimed invention combines two known techniques: a "split-and-mix" synthesis (Stage 1) to create bi-functional "carrier" molecules tagged with unique oligonucleotide identifiers, followed by a "templated" synthesis (Stage 2) where the carriers hybridize to a DNA template that facilitates chemical reactions between their molecule fragments.

3. Grounds for Unpatentability

Ground 1: Anticipation over WO ’008 - Claims 1, 2, 4, 5, 7-9, 16, 18-22, 27, 28-30, 32-33, 35-36, 38-39, and 46 are anticipated by WO ’008.

  • Prior Art Relied Upon: WO ’008 (Pedersen et al., WO 02/103008).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued WO ’008 discloses all elements for synthesizing DNA-encoded libraries of templated molecules. The reference’s "building blocks" were asserted to be identical to the ’381 patent’s "carrier molecules," comprising functional entities linked via a cleavable linker to "complementing elements" (oligonucleotide identifiers). Petitioner pointed to Example 108 of WO ’008, which describes preparing twelve different bi-functional carriers in separate reaction wells (meeting the split-and-mix steps of claim 1) and then admixing them. These carriers are then contacted with templates having specific coding regions, which directs codon-specific hybridization and subsequent reaction, meeting the limitations of independent claims 1 and 5, including the "region limitation" of claim 1. Dependent claims related to library size, cleavable linkers, and specific reaction types were also argued to be disclosed.

Ground 2: Anticipation over WO ’994 - Claims 1, 2, 4, 5, 7-9, 16, 18-23, 27, 28-30, 32-33, 35-36, 38-39, 45, and 46 are anticipated by WO ’994.

  • Prior Art Relied Upon: WO ’994 (Gouliaev et al., WO 2004/056994).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that WO ’994, which describes library synthesis using multiple templates, anticipates the challenged claims. The reference’s "Complementary Connector Polynucleotides" (CCPNs) were equated to the claimed bi-functional molecules, as they consist of molecule fragments attached to oligonucleotide identifiers via a linker. Petitioner argued that WO ’994 explicitly discloses preparing different CCPN carriers, admixing them into a pool, and then contacting this admixture with a pool of "Connector Polynucleotides" (CPNs) that act as templates. This process, exemplified by the synthesis of an encoded tripeptide in Example 1, was argued to meet every step of independent claims 1 and 5, including carrier synthesis, admixing, and contacting with a template that hybridizes to the identifier region.

Ground 3: Obviousness over WO ’825 and WO ’008 - Claims 1, 2, 4, 5, 7-9, 16, 18-22, 27, 28-30, 32-33, 35-36, 38-41, and 46 are obvious over WO ’825 in view of WO ’008.

  • Prior Art Relied Upon: WO ’825 (Freskgård et al., WO 2004/039825) and WO ’008 (Pedersen et al., WO 02/103008).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner argued that WO ’825 teaches methods for preparing bi-functional carrier molecules using a "Mode 2" split-and-mix synthesis, while WO ’008 teaches methods for template-encoded synthesis using such carriers. A person of ordinary skill in the art (POSA) would have found it obvious to prepare a library of carriers using the well-known split-and-mix techniques of WO ’825 and then use that library in the template-encoded reaction system disclosed in WO ’008.
    • Motivation to Combine: A POSA would combine these references because they address complementary aspects of the same process and were designed for such integration. Petitioner noted that WO ’825 explicitly states its "Mode 2" split-and-mix synthesis can be used to create intermediate libraries for a "Mode 1" one-pot templated synthesis. The motivation was to use the versatile carrier synthesis of WO ’825 to create large, diverse libraries for use in the efficient, high-yield templated reaction environment of WO ’008.
    • Expectation of Success: A POSA would have a high expectation of success, as the combination represents a simple substitution of one known type of DNA-encoded carrier (from WO ’825) for another (from WO ’008) in a known process. The structural and functional similarities of the carriers and templates would have made the outcome predictable.

  • Additional Grounds: Petitioner asserted additional anticipation and obviousness challenges against various claims based on WO ’627, WO ’929, and alternative obviousness theories over WO ’008 and WO ’994. An obviousness combination of WO ’929 and WO ’767 was also asserted against claims 42 and 43. These grounds relied on analogous arguments mapping disclosed carrier molecules, linkers, and synthesis steps to the claim limitations.

4. Key Claim Construction Positions

  • Petitioner argued for a specific construction of the term "template" based on the patent specification and prosecution history.
  • The proposed construction requires a "template" to be an entity that not only binds to carrier molecules but also actively promotes a chemical reaction between their molecule fragments, for instance by bringing them into reactive proximity. This construction was central to Petitioner's argument that the prior art references, which disclose entities that facilitate reactions via hybridization, indeed teach the claimed "templated synthesis."

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that its multiple grounds are not redundant and should not be denied under §325(d). It reasoned that each primary reference (WO ’627, WO ’008, WO ’994, and WO ’929) was not cited during prosecution and discloses distinct methods and species relevant to the ’381 patent claims.
  • For example, it was argued that WO ’994 is distinct because it teaches using multiple carriers with multiple templates, whereas WO ’008 focuses on hybridization to a single template. It was also argued that WO ’825 is distinct for its disclosure of specific carrier synthesis methods involving ligation and polymerase extension.

6. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1, 2, 4, 5, 7-9, 16, 18-23, 27-30, 32, 33, 35, 36, 38-43, 45, and 46 as unpatentable.