Trials@uspto.gov
`571.272.7822
`
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`
`
`
`
` Paper No. 15
`
` Entered: January 10, 2018
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`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`NUEVOLUTION A/S,
`Petitioner,
`
`v.
`
`CHEMGENE HOLDINGS APS,
`Patent Owner.
`____________
`
`Case IPR2017-01603
`Patent 8,951,728 B2
`____________
`
`
`Before SUSAN L. C. MITCHELL, ROBERT A. POLLOCK, and
`TIMOTHY G. MAJORS, Administrative Patent Judges.
`
`MAJORS, Administrative Patent Judge.
`
`
`
`
`
`
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`571.272.7822
`
`
`
`
`
`
` Paper No. 15
`
` Entered: January 10, 2018
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`NUEVOLUTION A/S,
`Petitioner,
`
`v.
`
`CHEMGENE HOLDINGS APS,
`Patent Owner.
`____________
`
`Case IPR2017-01603
`Patent 8,951,728 B2
`____________
`
`
`Before SUSAN L. C. MITCHELL, ROBERT A. POLLOCK, and
`TIMOTHY G. MAJORS, Administrative Patent Judges.
`
`MAJORS, Administrative Patent Judge.
`
`
`
`
`
`
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`
`IPR2017-01603
`Patent 8,951,728 B2
`
`
` INTRODUCTION
`Nuevolution A/S (“Petitioner”), on June 14, 2017, filed a Petition to
`institute inter partes review of claim 1 of U.S. Patent No. 8,951,728 B2
`(“the ’728 patent”). Paper 1. On September 8, 2017, Petitioner filed a
`corrected Petition. Paper 8 (“Pet.”). Chemgene Holdings APS (“Patent
`Owner”), on October 12, 2017, filed a Preliminary Response to the Petition.
`Paper 9 (“Prelim. Resp.”).
`Under 35 U.S.C. § 314(a), an inter partes review may not be instituted
`unless the Petition “shows that there is a reasonable likelihood that the
`petitioner would prevail with respect to at least 1 of the claims challenged in
`the petition.” For the reasons stated below, we determine that Petitioner has
`established a reasonable likelihood that it would prevail in showing the
`unpatentability of claim 1 of the ’728 patent. Thus, we institute an inter
`partes review of claim 1 of the ’728 patent.
`Related Proceedings
`A.
`Petitioner identifies no prior or pending litigation related to
`infringement or invalidity of the claims of the ’728 patent. Pet. 2.
`Petitioner, however, identifies proceedings in the United States District
`Court for the Eastern District of Virginia (Nuevolution A/S et al. v. Pedersen
`et al., No. 1:14-CV-00357 (E.D. Va)) and the Maritime and Commercial
`High Court in Denmark (Nuevolution A/S et al. v. Pedersen et al., T-16-12)
`related to correction of inventorship of the ’728 patent and/or Petitioner’s
`entitlement to rights in the ’728 patent (or its priority application —
`International Application No. PCT/DK2005/000747). Id. at 2–3. According
`to Petitioner, the district court dismissed the proceedings in the Eastern
`District of Virginia on the basis of forum non conveniens. Id. at 3.
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`Patent Owner provides further information about those proceedings.
`Patent Owner notes that the United States Court of Appeals for the Federal
`Circuit (Nuevolution A/S v. Chemgene Holdings APS, 593 F. App’x 907
`(Fed. Cir. July 19, 2017)) affirmed the district court’s dismissal. Prelim.
`Resp. 9; Ex. 2001 (affirming under Fed. Cir. R. 36). Regarding the
`proceedings in Denmark, Patent Owner asserts that, in February 2016, the
`“Court ruled that a 2007 Settlement Agreement between Nuevolution and
`Chemgene completely and perpetually bars Nuevolution from challenging
`Chemgene’s ownership of the PCT application and all related rights,
`including the ’728 patent.” Prelim. Resp. 9. According to Patent Owner,
`Nuevolution has appealed this ruling to the Danish Court of Appeal. Id.
`Petitioner also filed petitions for inter partes review of claims in
`related U.S. Patent No. 8,168,381 B2 (IPR2017-01598 and IPR2017-01599).
`Pet. 3. U.S. Patent No. 8,168,381 B2 (“the ’381 patent”) issued from the
`grandparent application to the ’728 patent. Id.; Exs. 1001, 1002.
`The ’728 Patent
`B.
`The ’728 patent relates generally to a method for synthesizing
`encoded molecules. Ex. 1002, 1:34–35. As background, the Specification
`explains that “[m]ethods are desired for increasing the efficiency of
`production and screening of chemical libraries with the purpose of
`generation and isolation of new compounds that can be used for applications
`in medicine, agriculture and other areas.” Id. at 1:40–43.
`According to the ’728 patent, known methods for production and
`screening of chemical libraries include DNA-encoding of compounds. Id. at
`1:64–17. More specifically, in one approach using “DNA-encoded libraries,
`each compound in the library is attached to a unique identifier that ‘encodes’
`the chemical structure of the molecule to which it is attached.” Id. at 2:1–4.
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`DNA-encoding in this way, the Specification explains, provides for more
`efficient screening and selection of compounds with desired characteristics
`(e.g., binding to a target) because “the isolated compound-DNA complexes
`can be identified at the end by PCR-amplification, cloning, and sequencing
`of the DNA portion.” Id. at 1:65–2:1; see also id. 1:40–63. In other words,
`“the structure of a molecule that is selected in [a] screening assay can easily
`be decoded by [an] attached unique identifier.” Id. at 2:4–6.
`As further background, the Specification discloses that DNA-encoded
`libraries have also been made with a templating approach. Id. at 2:6–7. “In
`this approach, DNA templates direct the synthesis of the encoded
`compounds.” Id. at 2:8–9. Recovered DNA-compound complexes can be
`amplified and used in subsequent rounds of DNA-templated synthesis. Id. at
`13–17.
`According to the Specification, “[t]he present invention combines the
`non-templated technique . . . with the template technique . . . and thereby
`provides an improved method for the generation of oligonucleotide-encoded
`libraries.” Id. at 2:21–24; see also id. Abstract (“The invention combines the
`advantages of split and mix synthesis with the advantages of template
`directed synthesis.”).
`The Specification defines several terms relevant to understanding the
`invention. Id. at 3:15–7:55. These definitions include, inter alia:
`Bi-functional molecule means a bi-functional molecule
`consisting of an encoded molecule (e.g. a low molecular weight
`organic molecule) and an oligonucleotide (e.g. a single- or
`double-stranded DNA molecule), where the oligonucleotide
`uniquely identifies the identity (structure) of the encoded
`molecule. The encoded molecule and the identifier are
`physically connected through a linker moiety.
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`Patent 8,951,728 B2
`Id. 3:17–24. The term “[c]arrier molecule” (used interchangeably with
`carrier and bi-functional carrier molecule) “is a bi-functional molecule that
`is employed in a Stage 2 templated synthesis, and may be generated by e.g.
`stage 1 [split and mix] synthesis.” Id. at 3:32–35. The Specification also
`defines an “[e]ncoded molecule” as “[t]he portion of the bi-functional
`molecule that is encoded by the oligonucleotide identifier of the bi-
`functional molecule.” Id. at 3:45–47. And the term “[i]dentifier” is defined
`as “[a]n oligonucleotide that encodes (specifies) the identity of the molecule
`fragment or encoded molecule to which it is attached.” Id. at 3:54–56.
`The Specification’s drawings are also helpful in understanding the
`invention. Figure 1, reproduced in part below, depicts an initial formation of
`bi-functional molecules as part of a “Stage 1” synthesis. Id. at 9:51–57.
`
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`Id. Fig. 1 (partial). Figure 1 shows that a linker molecule “L” is first added
`to wells (1 through m) in a microtiter plate. Id. at 9:63–64. This step is
`followed by addition of different amino acids (R, 1 through m) — “one type
`of amino acid per well (i.e., a specific amino acid to each well) . . . operably
`linked to the linker molecule.” Id. at 9:66–10:1. Then, an oligonucleotide
`identifier (O, 1 through m) is added to each well and operably linked to the
`linker molecule, such that “[e]ach well now contains a bi-functional
`molecule that consists of a linker molecule linked to an amino acid and an
`identifier oligonucleotide.” Id. at 10:3–7. In this way, “[t]he sequence of
`the oligo encodes the type of amino acid added to that well.” Id. at 10:9–10.
`After this initial process, the wells’ contents may be pooled and split
`into wells on a new microtiter plate, and a new round of synthesis applied.
`Id. at 10:14–19. For instance, by adding additional amino acids and
`oligonucleotide identifiers to the new wells, each well will contain a bi-
`functional molecule consisting of a di-peptide (two amino acids bound to
`each other) linked to a nucleotide sequence (two oligonucleotide identifiers
`bound to each other) encoding the di-peptide. Id. at 10:17–33, Fig. 1.
`The Specification also describes and illustrates a “Stage 2” templated
`synthesis. See, e.g., id. at 11:4–32, Fig. 2. This stage “essentially links
`together the bi-functional carrier molecules provided by stage 1 in different
`combinations.” Id. at 11:7–9. For example, as shown in Figure 2, the
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`method uses a DNA template that is complementary to a pair of bi–
`functional molecules.
`
`
`
`
`Id. Fig. 2 (partial). Figure 2 shows that by hybridizing the bi-functional
`molecules’ DNA/oligo portions to a complementary DNA template, the
`encoded molecules (e.g., di-peptide of each carrier) are brought close and
`allowed to react — transferring the encoded molecule of one bi-functional
`molecule to the other. Id. at 11:36–46. The reaction shown forms a
`tetrapeptide that is “linked . . . to a template that encodes the combination of
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`Patent 8,951,728 B2
`the di-peptides and thus, ultimately encodes the tetrapeptide.” Id. at 11:47–
`60.
`
`Illustrative Claim
`C.
`Petitioner challenges claim 1, the only independent claim of the
`’728 patent. Claim 1 reads as follows:
`1. A method for synthesizing an encoded molecule comprising
`the steps of:
`a) Adding a linker molecule L to one or more reaction
`wells;
`b) Adding a molecule fragment to each of said reaction
`wells;
`c) Adding an oligonucleotide identifier to each of said
`reaction wells;
`d) Subjecting said wells to:
`conditions sufficient to allow said molecule fragments and said
`oligonucleotide identifiers to become attached to said linker
`molecule, or
`conditions sufficient for said molecule fragments to bind to other
`molecule fragments and sufficient for said oligonucleotide
`identifiers to bind to other oligonucleotide identifiers;
`e) Combining the contents of said one or more reaction
`wells;
`wherein at least one reactive group of the linker
`molecule L reacts with a reactive group in the molecule
`fragment, or with a reactive group in the oligonucleotide;
`wherein at least one reactive group of the molecule
`fragments reacts with a reactive group in the linker molecule L,
`or with a reactive group in another molecule fragment,
`wherein at least one reactive group of the oligonucleotide
`identifiers reacts with a reactive group in the linker L, or with a
`reactive group in another oligonucleotide identifier; and
`wherein the region of the oligonucleotide identifier added
`to each well in step c), which hybridizes to said template
`identifies the molecule fragment added to the same well in
`step b).
`
`Ex. 1002, 137:1–138:17
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`Patent 8,951,728 B2
`The Asserted Grounds of Unpatentability
`D.
`Petitioner contends claim 1 is unpatentable under 35 U.S.C. §§ 102
`and/or 103 based on the following grounds. Pet. 6–7.
`Ground
`Reference(s)
`1
`Gouliaev ’6271
`
`2
`
`Pedersen2
`
`Basis
`§ 102
`
`§ 102
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`3
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`4
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`5
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`6
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`7
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`8
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`9
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`10
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`11
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`12
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`13
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`14
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`Pedersen
`
`Freskgård3
`
`Freskgård
`
`Freskgård and Pedersen
`
`Gouliaev ’9944
`
`Gouliaev ’994
`
`Franch ’9295
`
`Franch ’929
`
`Freskgård and Franch ’929
`
`Franch ’4276
`
`Franch ’427
`
`Freskgård and Franch ’427
`
`§ 103
`
`§ 102
`
`§ 103
`
`§ 103
`
`§ 102
`
`§ 103
`
`§ 102
`
`§ 103
`
`§ 103
`
`§ 102
`
`§ 103
`
`§ 103
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`
`1 Gouliaev et al., WO 03/078627 A2, publ. Sept. 25, 2003 (Ex. 1007).
`2 Pedersen et al., WO 02/103008 A2, publ. Dec. 27, 2002 (Ex. 1004).
`3 Freskgård et al., WO 2004/039825 A2, publ. May 13, 2004 (Ex. 1003).
`4 Gouliaev et al., WO 2004/056994 A2, publ. July 8, 2004 (Ex. 1006).
`5 Franch et al., WO 2004/024929 A2, publ. Mar. 25, 2004 (Ex. 1005).
`6 Franch et al., WO 2004/083427 A2, publ. Sept. 30, 2004 (Ex. 1016).
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`Petitioner also relies on the Declaration of Nicolas Winssinger, Ph.D.
`Ex. 1015.
`
`E. Overview of the Asserted References
`Gouliaev ’627
`
`i.
`
`Gouliaev ’627 relates to “[a] building block having the dual
`capabilities of transferring genetic information e.g. by recognising an
`encoding element and transferring a functional entity to a recipient reactive
`group.” Ex. 1007, Abstract. “The building block may be used in the
`generation of a single complex or libraries of different complexes, wherein
`the complex comprises an encoded molecule linked to an encoding
`element.” Id.; see also id. at 2:7–9 (“in an aspect of the present invention, an
`oligonucleotide conjugated to a transferable chemical moiety via a linker is
`provided, which has increased ability to transfer a functional entity.”).
`Gouliaev ’627 describes a building block having the general formula
`shown below.
`
`
`Id. at 2:10–19. As depicted, “FE” is a “functional entity,” “the lower
`horizontal line is a Complementing Element identifying the functional
`entity and the vertical line between the complementing element and the
`S atom is a Spacer.” Id. The spacer in combination with the depicted ring
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`Patent 8,951,728 B2
`member/moiety makes up a “cleavable linker.” Id. at 9:8–10, 9:26–27.
`Example 3 describes preparation of a building block like shown above. Id.
`at 32:15–33:29.
`Gouliaev ’627 also discloses a reaction between a building block and
`a receiving entity, so that the building block’s functional entity may be
`transferred to the receiving entity. Id. at 17:5–12. One example for such
`transfer is shown in Figure 1 below.
`
`
`
`Id. Fig. 1 (partial). As depicted in Fig. 1, “one complementing element of a
`building block recognizes a template carrying another functional entity,
`hence bringing the functional entities in close proximity” for functional-
`entity transfer. Id. at 17:12–14; see also id. at 34:19–35:5 (Example 5
`(describing transfer of a functional entity from a building block to a
`receiving template and disclosing the respective nucleotide sequences of the
`complementing element and the template’s complementary coding
`element)). According to Gouliaev ’627, “[p]referably, the complementing
`element is a sequence of nucleotides and the coding element is a sequence of
`nucleotides capable of hybridising to the complementing element.” Id. at
`10:20–24; see also id. 11:25–26 (“The coding element may comprise one,
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`Patent 8,951,728 B2
`two, three or more codons, i.e. sequences that may be specifically
`recognized by a complementing element.”).
` Pedersen
`ii.
`
`Pedersen relates to “a method for synthesizing template molecules”
`that “allows the generation of libraries which can be screened for e.g.
`therapeutic activity.” Ex. 1004, Abstract. More specifically, Pedersen
`discloses:
`The templated molecules are preferably synthesized from
`building blocks comprising a functional entity comprising a
`functional group and reactive group capable of covalently linking
`functional groups and forming a templated molecule. The
`functional entity of a building block is separated from a
`complementing element by a cleavable linker, or a selectively
`cleavable linker. The complementing element is capable of
`complementing a predetermined coding element of the template,
`thus ensuring a one-to-one relationship between a coding
`element - or a complementing element - and a functional entity,
`or a functional group.
`
`
`Id. at 13:18–26.
`
`Representative building blocks are shown in Pedersen’s drawings.
`Figure 3, for example, is reproduced below.
`
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`
`
`Id. Fig. 3. This figure shows a building block containing a functional entity,
`a cleavable linker, and a complementing element. Id.; see also id. at 27:15–
`25, Fig. 6. Pedersen discloses that “[t]he complementing element contains a
`recognition group that interacts with a complementary coding element
`(coding element not shown [in Fig. 3]).” Id. at 27:19–21. An exemplary
`method of synthesizing building blocks is disclosed in Examples 107 and
`108 of Pedersen. Id. at 298:13–303:32.
`
`Pedersen also discloses using building blocks in a templated synthesis.
`See, e.g., id. at 298:13–299:11, 301:1–303:32, Fig. 5A, Fig. 31. Figure 5A,
`for example, shows a templated synthesis and is reproduced below.
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`
`Id. Fig. 5A. According to Pedersen, this figure shows “[t]hree different
`complementing elements . . ., each linked to a specific functional entity
`[such as shown in the building blocks of Fig. 3]” and “[t]he right half of the
`figure includes the template which directs the incorporation of the building
`blocks by complementary base pairing [i.e., hybridization].” Id. at 28:4–9;
`see also id. at 47:23–48:2, Fig. 31, 301:29–303:17.
`iii. Freskgård
`
`Freskgård “relates to a method for obtaining a bifunctional complex
`comprising [a] display molecule part and a coding part,” as well as “a
`method for generation of a library of bifunctional complexes.” Ex. 1003,
`1:10–13. Freskgård teaches these libraries may be formed by so-called
`“Mode 1” (one-pot synthesis) and “Mode 2” (split-and-mix synthesis)
`methods, or “advantageous[ly] through combinations of these methods.” Id.
`at 11:18–12:16, 27:12–29, 35:30–36:34.
`Freskgård teaches the synthesis of various types of building blocks
`and bi-functional molecules in the formation of a library of complexes. See,
`e.g., id. at 5:29–6:17, 95:5–13, Figs. 1–2, 11–13. According to Freskgård,
`“[a] functional entity attached to a nucleic acid may be referred to [] as a
`building block and specifies a chemical entity in which the functional entity
`is capable of being reacted at the chemical reaction site.” Id. at 5:32–34.
`Freskgård discloses “[t]he oligonucleotide of the building block may or may
`not hold information as to the identity of the functional entity.” Id. at 6:1–2.
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`Further, in embodiments, the building block comprises an “anti-codon
`identifying the functional entity.” Id. at 6:5.
`Embodiments for synthesizing bi-functional molecules and libraries of
`molecules are illustrated in, for example, Figures 11–13 of Freskgård (e.g.,
`mode 2 or split-and-mix synthesis). Figure 13 is reproduced below.
`
`
`
`Id. Fig. 13. Figure 13 shows a 96-well microtiter plate to the left and, to the
`right, a process for forming bi-functional molecules/complexes. Id. at 95:5–
`32. More specifically, Freskgård teaches a reactive group (Rx) attached to
`an oligonucleotide (horizontal line) is dispensed into the variety of the wells.
`Id. at 95:25–27. Then, “[i]n a first step, the reactive group in each
`compartment is reacted with a reactant, in a second step a codon
`oligonucleotide and a splint is added together with a ligase to ligate
`covalently the codon oligonucleotide to the reacted nascent bifunctional
`complex, and in a third step the ligation product is recovered.” Id. at 27–30.
`According to Freskgård, “[t]he content of the wells may subsequently be
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`Patent 8,951,728 B2
`combined and used as a library of bifunctional complexes or recycled for
`another round of reaction and addition of tag.” Id. at 95:30–32; see also id.
`Fig. 11–12,7 93:11–95:22.) Freskgård discloses further methods for forming
`bi-functional carrier molecules according to a Mode 2 synthesis. See, e.g.,
`id. 133:15–140:4 (Example 7), 151:10–154:6 (Example 9).
`Freskgård also discloses examples of Mode 1 synthesis including a
`“three-strand” procedure that employs an “assembly platform” to which
`specific carrier molecules hybridize. Id. Fig. 7, 26:4–16, 92:18–26. This
`procedure is illustrated in Freskgård’s Figure 7, which is reproduced below.
`
`
`
`
`
`
`7 Freskgård teaches that “Fig. 13 outlines an embodiment with the encoding
`and reaction step reversed compared to the embodiment shown in Fig. 12.”
`Ex. 1003, 95:24–25. In other words, in Figure 12, the reactant (e.g., codon-
`specific drug fragment) is added and attached to the reactive group/linker
`after attachment of a codon-oligonucleotide. Id. Fig. 12, 95:5–22.
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`Id. Fig. 7. Figure 7 shows “[t]he identifier and building block can be
`assembled on an assembly platform,” to allow for functional entity transfer
`from the carrier molecule to the attachment entity of the identifier. Id.; see
`also id. 26:4–16, 92:18–26. Freskgård teaches “[t]he assembly platform []
`contains a unique anticodon region with a specific sequence . . . [that] will
`anneal [i.e., hybridize] to the unique codon region in the carrier.” Id. at
`26:10–13;8 see also id. at 127:23–129:11, 133:16–140:18, 143:4–144:16.
`iv. Gouliaev ’994
`
`Gouliaev ’994 relates to “synthesis of molecules guided b[y]
`connector polynucleotides” (CPNs) “capable of hybridizing to
`complementary connector ploynucleotides [sic]” (CCPNs) having “at least
`one functional entity comprising at least one reactive group.” Ex. 1006,
`Abstract.
`CCPNs (i.e., bi-functional carrier molecules) are shown in Figure 1 of
`Gouliaev ’994:
`
`
`
`
`8 Freskgård further teaches “[t]he unique anticodon [on the platform] can
`either be identical to the unique anticodon region or a shorter or longer
`sequence . . . [and] [t]he sequence of the unique anticodon can be used to
`decode the unique anticodon region . . . [that] codes for the functional
`entity.” Id. at 26:18–24.
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`For example, Fig. 1C (reproduced above) depicts a CCPN comprising a
`linker attached to a polynucleotide and a functional entity with multiple
`reactive groups. Id. Fig. 1C. Gouliaev ’994 teaches “a CCPN may specify
`for the annealing of a specific type of CPN.” Id. at 57:32–33; see also id.
`62:25–36 (“CCPNs, in their hybridizing domains specify/signal the need for
`specific reaction partners.”) Example 1 of Gouliaev ’994 discloses a method
`for synthesizing CCPNs. Id. at 76:1–77:4.
`
`By pooling CCPNs with CPNs, a library of hybridization complexes
`are formed. Id. Fig. 10. More specifically, CPNs act as a template having
`descriptor/polynucleotide regions that hybridize to complementary
`descriptor regions on CCPNs, such as shown in the illustration from
`Gouliaev ’929 below. Id. at 61:7–62:23.
`
`
`
`Id. at 62:1–11. This illustration discloses a CPN with distinct hybridizing
`regions for two CCPN carrier molecules. In embodiments, Gouliaev ’994
`teaches, “a CPN sequence is designed so as to anneal to one specific CCPN-
`sequence . . . giv[ing] a one-to-one relationship between the functional entity
`descriptor (e.g., a polynucleotide based codon) and encoded functional
`entity.” Id. at 58:34–59:2.
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`Franch ’929
`v.
`
`Franch ’929 relates to “a method for synthesizing a bifunctional
`complex . . . [that] comprises a template as well as a molecule, the synthesis
`of which is being directed by the template,” and the formation of a library of
`such complexes. Ex. 1005, Abstract. Franch ’929 discloses “a template
`comprising two or more codons in sequence, a first pair of a molecular
`affinity pair, and a reactive group.” Id. Further, the method of Franch ’929
`uses “two or more building blocks, each of which comprises i) an anti-codon
`capable of recognising a codon of the template, ii) a functional entity
`comprising at least one reactive group, and iii) a linker connecting the anti-
`codon and the functional entity.” Id; see also id. 4:2–26. Franch ’929
`teaches “contacting the template with a building block under conditions
`which allow specific hybridisation of the anti-codon of the building block to
`the codon of the template.” Id. at 4:16–18.
`Figure 1 of Franch ’929, reproduced below, is a schematic
`representation of this hybridization between building blocks and a template.
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`Id. Fig. 1. Figure 1 shows, inter alia, the step-wise hybridization of building
`blocks (oligos O1, O2, O3) to a template having a scaffold with reactive
`groups (Y) for accepting for transfer of molecule fragments (R1, R2, R3)
`from the respective building blocks. Id.; see also id. 52:18–55:2. After the
`template, which contains three codons, is coupled to a scaffold, “building
`block O1 is annealed to the template. The building block comprises the
`anticodon (A-cdn 1) which complements codon 1 of the template.” Id. at
`52:22–27. Then, “the functional entity [R1] of the first building block is
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`transferred to the scaffold by a direct reaction involving the reactive
`groups X and Y.” Id. at 52:30–32. The process continues similarly for
`building blocks O2 and O3 as shown. Id. Fig. 1; see also Fig. 6.
`Examples 1 and 2 of Franch ’929 describe the preparation of building
`blocks, such as used in the process shown above. Id. at 72:1–75:32.
`Franch ’427
`vi.
`
`Franch ’427 “relates to a method for synthesizing a bifunctional
`complex comprising an encoded molecule and an identifier polynucleotide
`identifying the chemical entities having participated in the synthesis of the
`encoded molecule.” Ex. 1016, Abstract; see also id. at 5:8–10.
`Franch ’427 discloses, inter alia, providing “at least one template
`comprising one or more codons capable of hybridising to an anti-codon,
`wherein said template is optionally associated with one or more chemical
`entities,” and providing “a plurality of building blocks each comprising an
`anti-codon associated with one or more chemical entities.” Id. at 5:14–20.
`After “hybridising the anti-codon of one or more of the provided building
`blocks to the template,” the anti-codons may be linked and/or the template is
`linked with the anti-codon of at least one building block, thereby “generating
`an identifier polynucleotide capable of identifying chemical entities having
`participated in the synthesis of the encoded molecule.” Id. at 5:22–28.
`An example of this synthesis is shown in Figure 2 of Franch ’427, in
`which multiple building blocks are combined on a template. Id. at 67:7–26.
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`Id. Fig. 2. As shown in Figure 2, “a template comprising a hairpin loop is
`provided” and “[v]arious building blocks are added subsequently.” Id. at
`67:13–18. According to Franch ’427, “[t]he anticodons [of the building
`blocks] are designed such that they align[] on the template under
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`hybridisation conditions,” which “is directed by the sequence of the
`template.” Id. at 67:18–20. The “anticodons are ligated together,” and “the
`ligation product is made single stranded by inducing denaturing conditions,”
`which then allows the chemical entities to react together and form the
`reaction product. Id. at 67:20–26; see also id. Fig. 2.
`
`Franch ’427 provides a more detailed description of the chemical
`structure of building blocks capable of transferring a chemical entity. See,
`e.g., id. at 49:9–50:16. One example is essentially a building block with the
`same structure as in Gouliaev ’627. Compare id. 49:12–50:1 with Ex. 1007,
`2:10–19; see supra Section I(E)(i). Franch ’427 discloses that this “building
`block is the subject of Danish patent application No. PA 2002 01946 and the
`US provisional patent application No. 60/434,439 [(Ex. 1017) “the ’439
`Application”], the content of which are incorporated herein in their entirety.”
`Ex. 1016, 50:1–4. The ’439 Application discloses a method for synthesis of
`this building block. Ex. 1017, 2:10–19, 16:16–17:28 (Example 3).9
` ANALYSIS
`Person of Ordinary Skill in the Art
`A.
`Petitioner asserts that, as of November 22, 2004, a person of ordinary
`skill in the art would have been one “with a Ph.D. in organic chemistry,
`molecular biology or a closely related field [, and] with a minimum of 3-5
`years of additional experience in medicinal chemistry with an emphasis on
`drug discovery.” Pet. 21; Ex. 1015, ¶¶ 30–32. For its part, Patent Owner
`asserts the ordinarily skilled person “would have held a doctoral degree in
`
`
`9 Gouliaev ’627 also claims priority to the ’439 Application. Ex. 1007. The
`method of synthesis of this building block also appears to be substantially
`the same in Gouliaev ’627 and the ’439 Application. Compare Ex. 1007,
`32:15–33:28 with Ex. 1017, 16:16–17:28.
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`chemistry, molecular biology, or a closely related discipline, and had at least
`three years of practical academic or industrial laboratory experience.”
`Prelim. Resp. 10.
`Although not identical, Petitioner and Patent Owner propose similar
`qualifications of the skilled artisan. We do not, for purposes of this
`Decision, discern a material difference between the parties’ proposals. As
`the parties’ proposals are not inconsistent with the prior art of record, and as
`Petitioner bears the burden, we rely on Petitioner’s proposal for the purposes
`of this Decision, but our analysis would be the same under either proposal.
`See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (explaining
`that specific findings regarding ordinary skill level are not required “where
`the prior art itself reflects an appropriate level and a need for testimony is
`not shown”) (quoting Litton Indus. Prods., Inc. v. Solid State Sys. Corp., 755
`F.2d 158, 163 (Fed. Cir. 1985)).
`Claim Construction
`B.
`In an inter partes review, we interpret claim terms in an unexpired
`patent based on the broadest reasonable construction in light of the
`specification of the patent in which they appear. 37 C.F.R. § 42.100(b);
`Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2142 (2016) (affirming
`the broadest reasonable construction standard in inter partes review
`proceedings). Under that standard, and absent any special definitions, we
`presume a claim term carries its “ordinary and customary meaning,” which
`“is the meaning the term would have to a person of ordinary skill in the art
`in question” at the time of the invention. In re Translogic Tech., Inc., 504
`F.3d 1249, 1257 (Fed. Cir. 2007). Any special definitions must be set forth
`with reasonable clarity, deliberateness, and precision. In re Paulsen, 30 F.3d
`1475, 1480 (Fed. Cir. 1994). We need only construe terms in controversy,
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`and only to the extent necessary to resolve that controversy. Vivid Techs.,
`Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999).
`Petitioner notes that several of the claim terms are defined in the
`Specification, including “encoded molecule,” “identifier,” and “well.”
`Pet. 21–22. Although not expressly stated in the Petition, we understand
`Petitioner to contend that the broadest reasonable interpretation of these
`terms is controlled by the ’728 patent’s definitions.
`Petitioner also proposes an interpretation for the term “template.”
`Pet. 22–23. That term appears only in the following phrase of claim 1: “the
`region of the oligonucleotide identifier added to each well in step c), which
`hybridizes to said template identifies the molecule fragment added to the
`same well in step b).” Ex. 1002, 138:13–17 (emphasis added).10 Petitioner
`asserts that, under the broadest reasonable interpretation consistent with the
`Specification, “a POSA would understand the term ‘template’ to be ‘an
`entity capable of binding carrier molecule(s) to bring molecule fragment(s)
`into reactive proximity with another reactive group.’” Pet. 23 (quoting
`Ex. 1015, ¶¶ 93–95).
`In response, Patent Owner asserts that “no claim term requires express
`construction.” Prelim. Resp. 10.
`After receiving Patent Owner’s Preliminary Response, Petitioner
`sought the Board’s leave for further briefing on the limitation of “each of
`
`
`10 Although the phrase “said template” appears in this portion of claim 1, the
`term “template” does not appear elsewhere in the claim, thus a specific
`antecedent basis for the term is lacking. Compare Ex. 1002, 138:13–17 with
`Ex. 1001, 135:57–60 (reciting a
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