PETITION FOR INTER PARTES REVIEW
`U.S. PATENT NO. 7,790,869
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In Re: US. Patent of Jingyue Ju. et al.
`Patent No.: 7,790,869
`Appl. No.: 11/810,509
`Issue Date: September 7, 2010
`For:
`MASSIVE PARALLEL METHOD FOR DECODING DNA
`AND RNA
`
`
`MAIL STOP PATENT BOARD
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PAT. No. 7,790,869
`
`Inter partes review of U.S. Patent 7,790,869 ("the '869 patent") pursuant to
`
`35 US.C. § 311 and 37 C.F.R. §§ 42.1 et seq. is respectfully requested by
`
`Petitioner Illumina, Inc. ("Petitioner"). Petitioner submits that the attached prior
`
`art (attached as Exhibits 1002 to 1020) renders claims 12-13, 15-17, 20-26, 28-29,
`
`31, and 33 of the '869 patent invalid under 35 U.S.C. §§ 102(a), 102(b), 102(e),
`
`and 103(a) and raises a reasonable likelihood that Petitioner will prevail with
`
`respect to at least one of claims 12-13, 15-17, 20-26, 28-29, 31, and 33 of the '869
`
`patent. Accordingly, it is requested that inter partes review be instituted and that
`Columbia Ex. 2041
`Illumina, Inc. v. The Trustees
`claims 12-13, 15-17, 20-26, 28-29, 31, and 33 of the '869 patent be found invalid.
`of Columbia University
` York
`in the City of New
`IPR2020­01177
`
`
`
`

`

`
`
`PETITION FOR INTER PARTES REVIEW
`U.S. PATENT NO. 7,790,869
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In Re: US. Patent of Jingyue Ju. et al.
`Patent No.: 7,790,869
`Appl. No.: 11/810,509
`Issue Date: September 7, 2010
`For:
`MASSIVE PARALLEL METHOD FOR DECODING DNA
`AND RNA
`
`
`MAIL STOP PATENT BOARD
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PAT. No. 7,790,869
`
`Inter partes review of U.S. Patent 7,790,869 ("the '869 patent") pursuant to
`
`35 US.C. § 311 and 37 C.F.R. §§ 42.1 et seq. is respectfully requested by
`
`Petitioner Illumina, Inc. ("Petitioner"). Petitioner submits that the attached prior
`
`art (attached as Exhibits 1002 to 1020) renders claims 12-13, 15-17, 20-26, 28-29,
`
`31, and 33 of the '869 patent invalid under 35 U.S.C. §§ 102(a), 102(b), 102(e),
`
`and 103(a) and raises a reasonable likelihood that Petitioner will prevail with
`
`respect to at least one of claims 12-13, 15-17, 20-26, 28-29, 31, and 33 of the '869
`
`patent. Accordingly, it is requested that inter partes review be instituted and that
`
`claims 12-13, 15-17, 20-26, 28-29, 31, and 33 of the '869 patent be found invalid.
`
`
`
`

`

`
`
`TABLE OF CONTENTS
`
`I.
`
`II.
`
`INTRODUCTION ........................................................................................... 2
`
`REQUIREMENTS FOR INTER PARTES REVIEW UNDER
`35 U.S.C. § 312 and 37 C.F.R. §§ 42.1 - 42.123 ............................................. 2
`
`III. OVERVIEW OF THE '869 PATENT AND SUMMARY OF
`INVALIDATING PRIOR ART REFERENCES ............................................ 9
`
`A.
`
`B.
`
`Summary of the '869 Patent and Invalidating Prior Art ........................ 9
`
`Scope and Content of the Prior Art Relating to Nucleotides and
`dNTPs Having Deaza-Substituted Bases ............................................ 14
`
`C.
`
`Summary of the Prosecution History of the '869 Patent ..................... 16
`
`IV. STATEMENT REGARDING CONSTRUCTION OF THE
`CHALLENGED CLAIMS ............................................................................ 17
`
`A.
`
`B.
`
`Claim Construction Standard .............................................................. 17
`
`Discussion of Individual Claim Terms ............................................... 18
`
`V. DETAILED EXPLANATION OF PETITIONER'S BASIS FOR
`CHALLENGING CLAIMS 12-13, 15-17, 20-26, 28-29, 31, and 33
`OF THE '869 PATENT DEMONSTRATING A REASONABLE
`LIKELIHOOD OF PREVAILING AGAINST THE CLAIMS OF
`THE '869 PATENT ....................................................................................... 20
`
`1.
`
`2.
`
`3.
`
`4.
`
`
`
`Ground for Challenge 1 - Claims 12-13, 15-17, 20-26, 28-29,
`31, and 33 of the '869 patent are invalid as anticipated by Tsien ....... 21
`
`Ground for Challenge 2 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Tsien and Prober I .......................... 27
`
`Ground for Challenge 3 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Tsien and Prober II ........................ 29
`
`Ground for Challenge 4 - Claims 12-13, 15-17, 20-26, 28-29,
`31, and 33 of the '869 patent are invalid as anticipated by
`Dower .................................................................................................. 32
`
`ii
`
`

`

`
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Ground for Challenge 5 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Dower and Prober I ........................ 39
`
`Ground for Challenge 6 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Dower and Prober II ...................... 40
`
`Ground for Challenge 7 - Claims 12-13, 17, 20-26, 28-29, 31,
`and 33 of the '869 patent are invalid as anticipated by Rabani ........... 42
`
`Ground for Challenge 8 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Rabani and Prober I ....................... 46
`
`Ground for Challenge 9 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Rabani and Prober II ...................... 47
`
`10. Ground for Challenge 10 - Claims 12-13, 15-17, 20-26, 28-29,
`31, and 33 of the '869 patent are invalid as anticipated by
`Stemple II ............................................................................................ 47
`
`11. Ground for Challenge 11 - Claims 12-13, 15-17, 20-26, 28-29,
`31, and 33 of the '869 patent are invalid as anticipated by
`Stemple III ........................................................................................... 54
`
`12. Ground for Challenge 12 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Stemple II and Anazawa ............... 54
`
`13. Ground for Challenge 13 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Stemple III and Anazawa et
`al. ......................................................................................................... 55
`
`14. Ground for Challenge 14 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Stemple II and Prober I ................. 55
`
`15. Ground for Challenge 15 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Stemple III and Prober I ................ 56
`
`16. Ground for Challenge 16 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Tsien and Hobbs ............................ 57
`
`17. Ground for Challenge 17 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Dower and Hobbs et al. .................. 58
`
`
`
`iii
`
`

`

`
`
`18. Ground for Challenge 18 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Stemple II and Hobbs et al.. ........... 59
`
`19. Ground for Challenge 18 - Claims 15 and 16 of the '869 patent
`are invalid as obvious in view of Stemple III and Hobbs et al. .......... 59
`
`VI. CONCLUSION .............................................................................................. 59
`
`
`
`
`
`
`
`
`
`
`
`iv
`
`

`

`
`
`TABLE OF PRIOR ART REFERENCES
`
`Exhibit 1001 - The '869 patent (U.S. Patent 7,790,869 to Jingyue Ju et al.)
`
`Exhibit 1002 - Tsien (PCT Publication WO 91/06678 to Tsien et al.)
`
`Exhibit 1003 - Prober I (Prober et al., Science 238, 336-341 (1987)
`
`Exhibit 1004 - Prober II (U.S. Patent No. 5,242,796 to Prober)
`
`Exhibit 1005 - Dower (U.S. Patent No. 5,547,839 to Dower et al.)
`
`Exhibit 1006 - Rabani (PCT Publication WO 96/27025 to Rabani)
`
`Exhibit 1007 - Stemple II (PCT Publication WO 00/53805 to Stemple et al.)
`
`Exhibit 1008 - Stemple III (U.S. Patent No. 7,270,951 to Stemple et al.)
`
`Exhibit 1009 - Stemple I (U.S. application serial no. 09/266,187 to Stemple et al.)
`
`Exhibit 1010 - PCT Publication WO 98/33939 to Anazawa et al. (Japanese
`language version)
`
`Exhibit 1011 - Anazawa (English translation of WO 98/33939)
`
`Exhibit 1012 - Translation Affidavit for Anazawa
`
`Exhibit 1013 - Hobbs (U.S. Patent No. 5,047,519 to Hobbs et al.)
`
`Exhibit 1014 - Seela I (U.S. Patent No. 4,804,748 to Seela et al.)
`
`Exhibit 1015 - Seela II (U.S. Patent No. 5,844,106 to Seela et al.)
`
`Exhibit 1016 - Saiki (WO 89/11548 to Saiki)
`
`Exhibit 1017 - P. Williams (U.S. Pat. No. 7,037,687 to Williams et al.)
`
`Exhibit 1018 - J. Williams (U.S. Pat. No. 6,255,083 to Williams)
`
`
`
`v
`
`

`

`
`
`Exhibit 1019 - Canard (U.S. Pat. No. 6,001,566 to Canard)
`
`Exhibit 1020 - Rosenthal (PCT Publication WO 93/21340 to Rosenthal et al.)
`
`Exhibit 1021 - Declaration of George Weinstock, Ph.D.
`
`Exhibit 1022 - Excerpts from the '869 Patent File History
`
`
`
`
`
`
`
`
`
`
`
`
`
`vi
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`

`

`PETITION FOR INTER PARTES REVIEW
`U.S. PATENT NO. 7,790,869
`
`I.
`
`INTRODUCTION
`Inter partes review of U.S. Patent No. 7,790,869 ("the '869 patent") and
`
`cancellation of at least claims 12-13, 15-17, 20-26, 28-29, 31, and 33 ("the
`
`challenged claims") under 35 U.S.C. §§ 102 and 103 is respectfully requested. A
`
`copy of the '869 patent is attached as Exhibit 1001. Petitioner respectfully urges
`
`that this Petition be granted and examination conducted not only with "special
`
`dispatch," but also with "priority over all other cases" in accordance with MPEP
`
`§ 2661, due to the ongoing nature of the underlying litigation, discussed below.
`
`II. REQUIREMENTS FOR INTER PARTES REVIEW UNDER
`35 U.S.C. § 312 and 37 C.F.R. §§ 42.1 - 42.123
`Showing of a Reasonable Likelihood of Prevailing - the Petitioner
`
`A)
`
`submits that for the reasons discussed in detail below, there is a reasonable
`
`likelihood that the Petitioner will prevail with respect to the invalidity of at least
`
`one of the challenged claims as required under 35 U.S.C. § 314(a) and 37 C.F.R.
`
`§ 42.108. In particular, the prior art references accompanying this Petition show
`
`that the subject matter of the challenged claims was identically disclosed in the
`
`prior art and also that each of the challenged claims would have been obvious to a
`
`person of ordinary skill in the art. Further, none of the references accompanying
`
`this petition were substantively considered by the Examiner (although several of
`
`the references, including Dower, Tsien, Rabani, and Stemple II, were only
`
`Reinhart\8995609
`
`
`
`2
`
`

`

`
`
`provided as part of a 11 page information disclosure statement listing 161
`
`references). Accordingly, Petitioner respectfully requests that the inter partes
`
`review of the '869 patent be granted.
`
`B)
`
`Format Requirements - This Petition meets the paper, font, line
`
`spacing and margin requirements set forth 37 C.F.R. § 42.6(a).
`
`C) Certificate of Service - Pursuant to 37 C.F.R. § 42.6(e), a certificate
`
`of service in compliance with 37 C.F.R. § 42.6(e)(iii) is located at the end of this
`
`document showing that pursuant to 35 U.S.C. § 312(a)(5) and 37 C.F.R. §
`
`42.105(a), a copy of this petition, including all supporting documents, have been
`
`served in its entirety on the patent owner at the correspondence address of record:
`
`COOPER & DUNHAM, LLP, 30 Rockefeller Plaza, 20th Floor, New York, NY
`
`10112. Pursuant to 37 C.F.R. § 42.105(a), additional copies have been served on
`
`the patent owner at the following additional addresses: SHAW KELLER LLP, 300
`
`Delaware Avenue, Suite 1120, Wilmington, DE 19801, and MEDLEN &
`
`CARROLL, LLP, 100 Grandview Road, Suite 403, Braintree, MA 02184.
`
`D) Mandatory Notices - As required by 37 C.F.R. § 42.8, Petitioner
`
`hereby files the following notices:
`
`i) Real party-in-interest under 37 C.F.R. § 42.8(b)(1) - The real party in
`
`interest is Petitioner, Illumina, Inc. ("Illumina").
`
`ii) Related matters under 37 C.F.R. § 42.8(b)(2) - The '869 patent is the
`
`
`
`3
`
`

`

`
`
`subject of the litigation styled The Trustees of Columbia University in the City of
`
`NewYork v. Illumina, Inc., 1:12-cv-00376-UNA, currently pending in the United
`
`States District Court for the District of Delaware. The Patent Owner alleges that
`
`Illumina has and continues to infringe the '869 patent.
`
`Further, a petition for inter partes review of legally related U.S. Patent No.
`
`7,713,698 has been contemporaneously filed with the present petition.
`
`iii) Lead and backup counsel under 37 C.F.R. § 42.8(b)(3) - Pursuant to 37
`
`C.F.R. § 42.10, Petitioner designates Robert Lawler, Registration No. 62,075, as
`
`lead counsel, and James Morrow, Registration No. 32,505, as back-up counsel.
`
`The requisite power of attorney accompanies this petition.
`
`iv) Service Address under 37 C.F.R. § 42.8(b)(4) - Petitioner may be served
`
`electronically at ipadmin@reinhartlaw.com, and by postal mail and by hand
`
`delivery at Reinhart, Boerner, Van Deuren s.c., 1000 North Water St., Suite 1700,
`
`Milwaukee, WI 53202. The attorneys of record may be contacted by phone at
`
`414-298-1000.
`
`E) Required Fee - Pursuant to 35 U.S.C. § 312(a)(1) and 37 C.F.R.
`
`§ 42.103, the required petition fee has been paid from deposit account no. 18-0882.
`
`If additional fees are due or if an overpayment has been made, the Commissioner is
`
`authorized to deduct or credit the proper amount to deposit account no. 18-0882.
`
`F) Grounds for Standing - Pursuant to 37 C.F.R. § 42.104(a), Petitioner
`
`
`
`4
`
`

`

`
`
`certifies that the '869 patent is eligible for inter partes review, and that Petitioner is
`
`not barred or estopped from requesting inter partes review of the '869 patent.
`
`G)
`
`Identification of Challenges -Pursuant to 35 U.S.C. § 312(a)(3) and
`
`37 C.F.R. § 42.104(b)(1) and (2), the Petitioner requests review of claims 12-13,
`
`15-17, 20-26, 28-29, 31, and 33 of the '869 patent. The grounds on which the
`
`challenges to each claim are based are identified below:
`
`1.
`
`Claims 12-13, 15-17, 20-26, 28-29, 31, and 33 are anticipated under
`
`35 U.S.C. § 102(b) by PCT Publication WO 91/06678 to Tsien et al. published
`
`May 16, 1991 entitled DNA Sequencing ("Tsien," Exhibit 1002).
`
`2.
`
`Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over Tsien in
`
`view of A System for Rapid DNA Sequencing with Fluorescent Chain-
`
`Terminating Dideoxynucleotides, by Prober et al., Science 238, 336-341 (1987)
`
`published in 1987 ("Prober I"; Exhibit 1003).
`
`3.
`
`Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over Tsien in
`
`view of U.S. Patent No. 5,242,796 issued September 7, 1993 to Prober entitled
`
`Method, System and Reagents for DNA Sequencing ("Prober II"; Exhibit 1004).
`
`4.
`
`Claims 12-13, 17, 20-26, 28-29, 31, and 33 are anticipated under
`
`35 U.S.C. § 102(b) by U.S. Patent No. 5,547,839 issued August 20, 1996 to Dower
`
`et al. entitled Sequencing of Surface Immobilized Polymers Utilizing
`
`Microfluorescence Detection ("Dower," Exhibit 1005).
`
`
`
`5
`
`

`

`
`
`5.
`
`Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over Dower in
`
`view of Prober I.
`
`6.
`
`Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over Dower in
`
`view of Prober II.
`
`7.
`
`Claims 12-13, 17, 20-26, 28-29, 31, and 33 are anticipated under
`
`35 U.S.C. § 102(b) by PCT Publication WO 96/27025 to Rabani published
`
`September 6, 1996 entitled Device, Compounds, Algorithms, and Methods of
`
`Molecular Characterization and Manipulation with Molecular Parallelism
`
`("Rabani," Exhibit 1006).
`
`8.
`
`Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over Rabani
`
`in view of Prober I.
`
`9.
`
`Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over Rabani
`
`in view of Prober II.
`
`10. Claims 12-13, 15-17, 20-26, 28-29, 31, and 33 are anticipated under
`
`35 U.S.C. § 102(a) by International Application Publication WO 00/53805 to
`
`Stemple et al. published September 14, 2000 entitled A Method for Direct
`
`Nucleic Acid Sequencing ("Stemple II," Exhibit 1007).
`
`11. Claims 12-13, 15-17, 20-26, 28-29, 31, and 33 are anticipated under
`
`35 U.S.C. § 102(e) by U.S. Patent No. 7,270,951 issued September 18, 2007 to
`
`Stemple et al. entitled Method for Direct Nucleic Acid Sequencing, ("Stemple
`
`
`
`6
`
`

`

`
`
`III," Exhibit 1008), which claims priority under 35 U.S.C. § 120 as a continuation-
`
`in-part application of U.S. application serial no. 09/266,187 ("Stemple I," Exhibit
`
`1009), filed March 10, 1999.
`
`12. Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over
`
`Stemple II in view of PCT Publication WO 98/33939 to Anazawa et al., published
`
`August 6, 1998, entitled Method for Determining Nucleic Acids Base Sequence
`
`and Apparatus Therefor (Exhibit 1010). An English translation of WO 98/33939
`
`("Anazawa") is attached as Exhibit 1011, and an affidavit under 37 C.F.R.
`
`§ 42.63(b) is attached as Exhibit 1012.
`
`13. Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over
`
`Stemple III in view of Anazawa.
`
`14. Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over
`
`Stemple II in view of Prober I.
`
`15. Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over
`
`Stemple III in view of Prober I.
`
`16. Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over Tsien in
`
`view of U.S. Patent No. 5,047,519 issued September 10, 1991 to Hobbs et al.
`
`entitled Alkynylamino-Nucleotides ("Hobbs," Exhibit 1013).
`
`17. Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over Dower in
`
`view of Hobbs.
`
`
`
`7
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`

`

`
`
`18. Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over
`
`Stemple II in view of Hobbs.
`
`19. Claims 15 and 16 are obvious under 35 U.S.C. § 103(a) over
`
`Stemple III in view of Hobbs.
`
`Pursuant to 37 C.F.R. §§ 42.104(b)(4) and 42.104(b)(5), the details of how
`
`each challenged claim is unpatentable in view of each prior art reference, at least
`
`one instance of where each claim element can be found in the prior art and the
`
`supporting evidence relied upon are set forth in Section V below.
`
`H) Claim Construction - For purposes of this inter partes review
`
`Petition, the Patent Office will give the claim terms the "broadest reasonable
`
`construction in light of the specification of the patent in which it appears" (e.g., the
`
`ordinary and customary meaning) as required by 37 C.F.R. § 42.100(b) which
`
`states "A claim in an unexpired patent shall be given its broadest reasonable
`
`construction in light of the specification of the patent in which it appears."
`
`37 C.F.R. § 42.100. The interpretation and/or construction of the claims in the
`
`'869patent relevant to this inter partes review should not be viewed as constituting,
`
`in whole or in part, Petitioner's own interpretation and/or construction of such
`
`claims. Furthermore, Petitioner expressly reserves the right to present its own
`
`interpretation of such claims at a later time, which interpretation may differ, in
`
`whole or in part, from that presented herein.
`
`
`
`8
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`

`

`
`
`I)
`
`Copies of Submitted Prior Art - Pursuant to 35 U.S.C. § 312(a)(3), a
`
`copy of every patent and printed publication relied upon in this petition is
`
`submitted herewith.
`
`III. OVERVIEW OF THE '869 PATENT AND SUMMARY OF
`INVALIDATING PRIOR ART REFERENCES
`A.
`The '869 patent issued on September 7, 2010 from U.S. Application No.
`
`Summary of the '869 Patent and Invalidating Prior Art
`
`11/810,509 filed June 5, 2007. The '869 patent was filed as a continuation of
`
`application No. 10/702,203, filed on Nov. 4, 2003, now Pat. No. 7,345,159, which
`
`is a division of application No. 09/972,364, filed on Oct. 5, 2001, now Pat. No.
`
`6,664,079, claiming the benefit of provisional application No. 60/300,894, filed
`
`June 26, 2001, and is a continuation-in-part of application No. 09/684,670, filed on
`
`Oct. 6, 2000, now abandoned.
`
`The '869 patent is generally directed to a "sequencing by synthesis" method
`
`of determining the sequence of a polynucleic acid, such as DNA or RNA. See '869
`
`Abstract. In the sequencing by synthesis method of the '869 patent, 1) a nucleic
`
`acid template is attached to a solid support, 2) a primer hybridizes to the template,
`
`3) a polymerase adds a 3'-OH blocked and labeled nucleotide (i.e., a nucleotide
`
`including a capping group at the 3 position on the ribose of the nucleotide and a
`
`label that identifies the nucleotide base) to form a primer extension strand, 4) the
`
`unique label on the nucleotide is detected to determine the type of nucleotide that
`
`
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`9
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`

`

`
`
`was added by the polymerase, 5) removing the group capping the 3'-OH of the
`
`nucleotide that was incorporated into the primer extension strand, thereby
`
`permitting addition of further nucleotides, and 6) repeating the process to add and
`
`detect additional nucleotides added to the primer extension strand to determine the
`
`sequence of the nucleic acid template. See '869 patent, col. 8, lines 8-52. But see
`
`also Dower, Tsien, Rabani, and Stemple II and III. The 3'-OH capping group acts
`
`to ensure that only one base is incorporated into the growing primer extension
`
`strand at a time, and removal of the 3'-OH capping group then allows the next the
`
`nucleotide to be added by the polymerase. See '869 patent, col. 19, lines 52-65.
`
`A "nucleotide analogue" is defined in the '869 specification as "…a chemical
`
`compound that is structurally and functionally similar to the nucleotide, i.e. the
`
`nucleotide analogue can be recognized by polymerase as a substrate." '869 patent,
`
`col. 7, ll. 48-51. Specific examples provided in the '869 patent of "nucleotide
`
`analogues" are nucleotides having 7-deaza-adenine and 7-deaza-guanine as the
`
`nucleobase. See '869 patent, col. 7, ll. 58-63. The cleavable chemical group that
`
`"caps" or "blocks" the -OH group at the 3'-position of the sugar of the nucleotide
`
`analogue (i.e., prevents polymerase extension beyond a single base) can be any
`
`group that "1) is stable during the polymerase reaction, 2) does not interfere with
`
`the recognition of the nucleotide analogue by polymerase as a substrate, and 3) is
`
`cleavable." See '869 patent, col. 9, ll. 52-58. The only examples of 3'-OH
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`10
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`cleavable groups are -CH2OCH3 and -CH2CH=CH2. Id. The disclosed labels that
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`may be attached to the nucleotide analogues include a fluorescent moiety. Id. at
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`col. 9, l. 59 to col. 10, l. 35. The linker attaching the label to the nucleotide
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`analogue is a cleavable linker that can be cleaved by "…one or more of a physical
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`means, a chemical means, a physical chemical means, heat, and light." Id. at col.
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`10, ll. 45-48. The only specific example of a cleavable linker in the ‘869 patent is
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`a photocleavable 2-nitrobenzyl linker. See, e.g., id. at col. 23, ll. 29-35. The label
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`can be attached to the base of the nucleotide via a linker. The specific example
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`given in the '869 patent specification is "…a label is attached through a cleavable
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`linker to the 5-position of cytosine or thymine or to the 7-position of deaza-adenine
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`or deaza-guanine." Id. at col. 7, ll. 63-66. But see also Dower, Tsien, Rabani, and
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`Stemple II and III.
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`The ‘869 patent claims priority to Pat. No. 6,664,079. However, the ‘869
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`patent was not filed until well after Illumina announced and launched the first
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`commercial sequencing by synthesis system. While both the ‘869 patent and its
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`parent ‘079 patent are directed to sequencing by synthesis methods, the ‘869 patent
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`removed many of the original limitations of the ‘079 patent that the patentee
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`argued were important to their invention when prosecuting the ‘079 patent.
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`Independent claim 12, the only independent claim of the '869 patent
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`challenged in this petition for inter partes review, relates to nucleotide analog
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`11
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`usable in sequencing by synthesis methods and is reproduced in Claim Chart 1
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`below. Challenged claims 13, 15-17, 20-26, 28-29, 31, and 33 add additional
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`limitations to the nucleotide of claim 12.
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`However, the prior art submitted with this Petition shows that all of the
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`elements of the unjustifiably broadened claims of the '869 patent were both
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`identically disclosed and well known in the prior art. For example, Dower, Tsien,
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`Rabani and Stemple II and III all disclose nucleotides for use in sequencing by
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`synthesis methods identical to at least independent claim 12 of the '869 patent in
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`which 3'-OH capped (e.g., chain terminating) and labeled nucleotide analogs are
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`mixed with a primed nucleic acid template attached to a solid surface.
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`In fact, the Background of the Invention section of the '869 patent itself
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`confirms the teachings of the prior art submitted herewith. The '869 patent
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`Background section demonstrates that sequencing by synthesis was known at least
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`by 1988, stating: "The concept of sequencing DNA by synthesis without using
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`electrophoresis was first revealed in 1988 (Hyman, 1988)." See '869 patent, col. 2,
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`lines 9-10 (emphasis added). The '869 Applicant further admits that it was known
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`to couple the DNA template to a chip and to use labeled nucleotides, stating "Such
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`a scheme coupled with the chip format and laser-induced fluorescent detection has
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`the potential to markedly increase the throughput of DNA sequencing projects.
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`Consequently, several groups have investigated such a system with an aim to
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`12
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`construct an ultra high-throughput DNA sequencing procedure (Cheeseman 1994,
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`Metzker et al. 1994)." See '869 patent, col. 2, lines 13-19 (emphasis added).
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`Further, the '869 patent Background section demonstrates that it was known
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`to attach label groups to the nucleotide base, stating "it is known that modified
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`DNA polymerases (Thermo Sequenase and Taq FS polymerase) are able to
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`recognize nucleotides with extensive modifications with bulky groups such as
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`energy transfer dyes at the 5-position of the pyrimidines (T and C) and at the 7-
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`position of purines (G and A) (Rosenblum et al. 1997, Zhu et al. 1994)." See '869
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`patent, col. 2, lines 45-51 (emphasis added). The '869 Applicant admits that it was
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`known to use small chemical groups as 3'-OH blocking groups on nucleotides
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`during sequencing reactions stating "It is known that MOM (--CH 2OCH3) and allyl
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`(--CH 2CH=CH 2) groups can be used to cap an --OH group, and can be cleaved
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`chemically with high yield (Ireland et al. 1986; Kamal et al. 1999)." See '869
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`patent, col. 3, lines 26-29 (emphasis added). In fact, the MOM and allyl groups
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`identified as prior art in the background section of the '869 patent are the very
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`3'-OH capping groups that the '869 patent identifies as "embodiments of the
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`invention." See '869 patent, col. 12, lines 50-53, and FIG. 7.
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`Given the Applicant's understanding of the prior art as set forth in the
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`Applicant's own Background section and art of which they were aware, it is
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`unclear how the broadened claims of the '869 patent could be patentable.
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`B.
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`Scoppe and Conntent of thhe Prior A
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`dNTPPs Havingg Deaza-Suubstitutedd Bases
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`rt Relatinng to Nucleeotides an
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`Claims 15 aand 16 of tthe '869 pattent speciffy that the nnucleotidee "base is aa
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`B C
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`deazapuurine" (claiim 15) andd that the ddeazapurinne is one off "deaza-addenine andd
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`deaza-gguanine, eaach comprising a uniqque label aattached thrrough a cleeavable linnker
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`to a 7-position of deaza-adennine or deaaza-guaninne." (claim
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`16). In a
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`"7-
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`carbon atoom.
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`osition
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`deazapuurine," the natural 7-pposition nitrogen atomm is replacced with a
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`standard p
`For refeerence, the nucleobasse adenine is show beelow with s
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`numberrs shown inn red:
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`HHowever, reecitation oof a nucleottide or dNTTP having
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`a "deazap
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`urine" bas
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`and labeeling at thee 7-positionn of the deeazapurine,, as recitedd in claims
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`does noot render thhe claims patentable: use of nuccleotide annalogs incl
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`deazapuurine, and aa label attaached at thee 7-positioon thereof,
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`was well kknown in tthe
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`15 and 166,
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`nucleic acid sequeencing fieldd at least aas early as tthe late 19980s as shoown in a wiide
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`variety
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`of prior artt documennts. See WWeinstock DDecl. ¶ 37.
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`have beeen obviouss to substittute deaza bases for tthe regularr bases of thhe SBS
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`patents in view off the expresss motivatiion provideed by U.S.. Pat. No. 44,804,748 tto
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`14
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`Seela ("Seela I," Exhibit 1014). Seela I states that deaza bases can advantageously
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`be used in place of regular bases in polymerase-based sequencing methods. See,
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`e.g., id. at col. 4, lines 4-6; see also col. 2, lines 6-11 and 23-29. While much of
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`Seela I is directed to Sanger sequencing, Seela I states that this teaching about
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`using deaza bases is not limited to Sanger sequencing. See, e.g., id. at col. 4, lines
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`4-10.
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`In addition to the express statement in Seela I, multiple prior art references
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`recognized a number of advantages for using deazapurines as the base in
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`nucleotide analogs for sequencing. For example, the prior art teaches that
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`deazaguanine-based nucleotides allow for effective sequencing of cytosine-guanine
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`rich areas. See e.g., Seela I, col. 2, lines 31-33. Similarly, Prober I shows that
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`labels attached to the 7-position of deaza purines could be successfully
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`incorporated by polymerase. Prober I, page 340, col. 1.
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`Also, Hobbs reflects the synthesis scheme used to make the nucleotides of
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`Prober I. Hobbs teaches that the 7 position of a purine base is a particularly
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`advantageous location to place a label, as that location least interferes with the
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`incorporation of the nucleotide into a DNA strand by a polymerase. Hobbs, col. 8,
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`lines 54-60. Hobbs also teaches that when a label is placed at the advantageous
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`7 position of a purine base, the 7 position needs to be converted from an N to a C
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`(i.e. needs to be “deaza”) in order to form a stable glycosidic linkage between the
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`15
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`base and ribose portions of the nucleotide. See, e.g., Hobbs, col. 10, lines 67 - col.
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`11, line 4. In light of this express motivation in Hobbs, a person of ordinary skill
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`in the art would have been motivated to make the nitrogen to carbon substitution
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`(i.e. make the base a “deaza” base) when attaching a label to the 7 position of a
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`purine base of a nucleotide, as disclosed in the prior art discussed in the '869 patent
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`Background section. See '869 patent, col. 2, lines 45-51.
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`Third, the obvious interchangeability of regular and deaza bases is reflected
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`in the art. For example, Dower teaches that sequencing by synthesis methods
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`employing modified nucleotides having a 3'-OH "blocking agent" are "analogous
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`to the dideoxy nucleotides used in the Sanger and Coulson sequencing procedure,
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`but in certain embodiments here, the blockage is reversible." Dower, col. 14, ll.
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`53-56. Thus, Dower expressly teaches that art related to dideoxy nucleotides (i.e.,
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`Prober I, Prober II, Hobbs) is pertinent to the disclosed methods using nucleotide
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`that is "blocked at the position of '3 elongation." Id., col. 15, lines 33-35.
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`Similarly, Tsien teaches that the synthesis scheme for ddNTPs used in Prober I
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`should be used in Tsien to produce "fluorescent dNTPs." Tsien, p. 29, ll. 10-19.
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`Summary of the Prosecution History of the '869 Patent
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`C.
`The '869 patent issued on Sep. 7, 2010 from an application filed Jun. 5,
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`2007. The '869 patent is a continuation of application No. 10/702,203, filed on
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`Nov. 4, 2003, now Pat. No. 7,345,159, which is a division of application No.
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`09/972,364, filed on Oct. 5, 2001, now Pat. No. 6,664,079, and a continuation-in-
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`part of application No. 09/684,670, filed on Oct. 6, 2000, now abandoned.
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`The prosecution history of the '869 patent is remarkably sparse: the
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`Examiner did not make a single rejection over any prior art reference discussed in
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`this Petition, or any reference submitted during prosecution. In fact, the Examiner
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`entered only a single, non-final office action rejecting all claims for obviousness-
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`type double patenting over claims 1-18 of U.S. Patent No. 7,345,159 ("the '159
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`patent"). (See Exhibit 1022, Office Action dated 2009-07-10.) The Examiner
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`described both the pending '869 claims and those of the '159 patent as "not
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`patentably distinct from each other because they both claim nucleotide having a
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`base linked to a label via a cleavable linker and wherein the deoxyribose comprises
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`a chemical cleavable group capping the 3'OH group. Wherein the linkers can