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`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`Paper No. 1
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`______________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________________
`
`EnviroLogix Inc.
`Petitioner
`
`v.
`
`Ionian Technologies, Inc.
`Patent Owner
`
`Patent No. 9,562,263 (Claims 1-8 and 10-35)
`Issued: February 7, 2017
`Filed: October 30, 2013
`Inventors: Maples et al.
`Title: NICKING AND EXTENSION AMPLIFICATION REACTION FOR THE
`EXPONENTIAL AMPLIFICATION OF NUCLEIC ACIDS
`
`______________________
`
`
`
`Inter Partes Review No. 2018-00405
`
`
`
`PETITION FOR INTER PARTES REVIEW
`
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`TABLE OF CONTENTS
`Compliance with Requirements of Inter Partes Review Petition ................... 1 
`
`I. 
`
`A. 
`
`Certification that the Patent May Be Contested via Inter Partes
`Review by the Petitioner (37 CFR §§ 42.101 and 42.104) .................. 1 
`
`B. 
`
`Fee for Inter Partes Review (37 CFR § 42.15(a)) ............................... 1 
`
`C.  Mandatory Notices (37 CFR § 42.8(b)) ............................................... 1 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`Real Party in Interest (37 CFR § 42.8(b)(1)) .............................. 1 
`
`Other Proceedings (37 CFR § 42.8(b)(2)) .................................. 2 
`
`Lead and Backup Lead Counsel (37 CFR § 42.8(b)(3)) ............. 2 
`
`Service Information (37 CFR § 42.8(b)(4)) ................................ 2 
`
`D. 
`
`Proof of Service (37 CFR §§ 42.6(e) and 42.105(a)) ........................... 2 
`
`II. 
`
`Identification of Claims Being Challenged (37 CFR § 42.104(b)) ................. 3 
`
`III.  Relevant Information Concerning the Contested Patent ................................. 5 
`
`A. 
`
`B. 
`
`Person of Ordinary Skill in the Art ...................................................... 5 
`
`Prosecution History of the ‘263 Patent and Explanation under
`Sec. 325(d) ............................................................................................ 5 
`
`C. 
`
`Construction of Terms Used in the Claims .......................................... 7 
`
`1. 
`
`2. 
`
`General Observations .................................................................. 7 
`
`Constructions .............................................................................. 7 
`
`a. 
`
`b. 
`
`c. 
`
`d. 
`
`“a sample comprising a target nucleic acid” .................... 8 
`
`“a thermal denaturation step associated with
`amplification of the target polynucleotide sequence” ...... 8 
`
`“combining, in a single step, …” ...................................... 9 
`
`“bumper primers” ............................................................. 9 
`
`
`
`i
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`“polymerase” .................................................................. 10 
`
`“nicking enzyme” ........................................................... 10 
`
`“oligonucleotide comprising a 5′ portion that comprises a
`nicking enzyme binding site that is non-complementary
`to the target polynucleotide sequence and a 3′ portion that
`hybridizes to the target polynucleotide sequence” ......... 10 
`
`“amplification reagent mixture” ..................................... 11 
`
`“essentially isothermal conditions” ................................ 11 
`
`“real time” ....................................................................... 12 
`
`“duplex” .......................................................................... 12 
`
`“extending” ..................................................................... 13 
`
`e. 
`
`f. 
`
`g. 
`
`h. 
`
`i. 
`
`j. 
`
`k. 
`
`l. 
`
`m. 
`
`“genomic DNA” ............................................................. 13 
`
`D. 
`
`E. 
`
`Effective Filing Date of the ‘263 Patent ............................................ 13 
`
`Claims 1-6, 8, 10-13, 15-16, and 18-35 Are Anticipated by
`Ehses ................................................................................................... 14 
`
`1. 
`
`2. 
`
`The Teachings of Ehses ............................................................ 14 
`
`Ehses Anticipates Claim 1 ........................................................ 15 
`
`a. 
`
`b. 
`
`c. 
`
`d. 
`
`“A method of amplifying a target polynucleotide
`sequence, the method comprising …” ............................ 16 
`
`“…obtaining from an animal, plant or food, a sample
`comprising a target nucleic acid, the target nucleic acid
`comprising the target polynucleotide sequence…” ........ 17 
`
`“…without first subjecting the target nucleic acid to a
`thermal denaturation step associated with amplification
`of the target polynucleotide sequence…” ....................... 17 
`
`“…combining in a single step, the obtained sample
`directly with an amplification reagent mixture or diluting
`the obtained sample and combining, in a single step, the
`ii
`
`
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`diluted sample with an amplification reagent mixture, …
`the amplification reagent mixture being free of bumper
`primers …” ..................................................................... 18 
`
`“…comprising: (i) a polymerase…” ............................. 19 
`
`“… (ii) a nicking enzyme …” ......................................... 19 
`
`“… (iii) a first oligonucleotide comprising a 5′ portion
`that comprises a nicking enzyme binding site that is non-
`complementary to the target polynucleotide sequence and
`a 3′ portion that hybridizes to the target polynucleotide
`sequence, and (iv) a second oligonucleotide comprising a
`5′ portion that comprises a nicking enzyme binding site
`that is non-complementary to the target polynucleotide
`sequence and a 3′ portion that hybridizes to the target
`polynucleotide sequence…” ........................................... 19 
`
`“…subjecting the reaction mixture formed by the step of
`combining to essentially isothermal conditions to amplify
`the target polynucleotide sequence without the assistance
`of bumper primers …” .................................................... 20 
`
`“…detecting the amplified target polynucleotide
`sequence in real time…” ................................................. 21 
`
`“…within 10 minutes of subjecting the reaction mixture
`to essentially isothermal conditions.” ............................. 22 
`
`e. 
`
`f. 
`
`g. 
`
`h. 
`
`i. 
`
`j. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
`
`Ehses Anticipates Claims 2-4 ................................................... 22 
`
`Ehses Anticipates Claims 5-6, 8, 10, and 11 ............................ 25 
`
`Ehses Anticipates Claims 12-13 ............................................... 25 
`
`Ehses Anticipates Claims 15-16 ............................................... 26 
`
`Ehses Anticipates Claim 18 ...................................................... 26 
`
`Ehses Anticipates Claim 19 ...................................................... 27 
`
`Ehses Anticipates Claim 20 ...................................................... 27 
`
`
`
`iii
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`10.  Ehses Anticipates Claim 21 ...................................................... 27 
`
`11.  Ehses Anticipates Claim 22 ...................................................... 28 
`
`12.  Ehses Anticipates Claim 23 ...................................................... 28 
`
`13.  Ehses Anticipates Claims 24-34 ............................................... 29 
`
`14.  Ehses Anticipates Claim 35 ...................................................... 29 
`
`F. 
`
`Claims 1-6, 8, 10-13, 15-16, and 18-35 Are Anticipated by
`Ehses-Dissertation .............................................................................. 30 
`
`1. 
`
`2. 
`
`The Teachings of Ehses-Dissertation ....................................... 30 
`
`Ehses-Dissertation Anticipates Claim 1 ................................... 31 
`
`a. 
`
`b. 
`
`c. 
`
`d. 
`
`e. 
`
`f. 
`
`g. 
`
`“A method of amplifying a target polynucleotide
`sequence, the method comprising …” ............................ 31 
`
`“…obtaining from an animal, plant or food, a sample
`comprising a target nucleic acid, the target nucleic acid
`comprising the target polynucleotide sequence…” ........ 31 
`
`“…without first subjecting the target nucleic acid to a
`thermal denaturation step associated with amplification
`of the target polynucleotide sequence…” ....................... 32 
`
`“…combining in a single step, the obtained sample
`directly with an amplification reagent mixture…or
`diluting the obtained sample and combining, in a single
`step, the diluted sample with an amplification reagent
`mixture, …the amplification reagent mixture being free
`of bumper primers…” ..................................................... 32 
`
`“…and comprising: (i) a polymerase…” ....................... 33 
`
`“…(ii) a nicking enzyme…” ........................................... 33 
`
`“… (iii) a first oligonucleotide comprising a 5′ portion
`that comprises a nicking enzyme binding site that is non-
`complementary to the target polynucleotide sequence and
`a 3′ portion that hybridizes to the target polynucleotide
`
`
`
`iv
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`sequence, and (iv) a secon oligonucleotide comprising a
`5′ portion that comprises a nicking enzyme binding site
`that is non-complementary to the target polynucleotide
`sequence and a 3′ portion that hybridizes to the target
`polynucleotide sequence …” .......................................... 33 
`
`h. 
`
`i. 
`
`j. 
`
`“…subjecting the reaction mixture formed by the step of
`combining to essentially isothermal conditions to amplify
`the target polynucleotide sequence without the assistance
`of bumper primers…” ..................................................... 34 
`
`“…detecting the amplified target polynucleotide
`sequence in real time…” ................................................. 35 
`
`“…within 10 minutes of subjecting the reaction mixture
`to essentially isothermal conditions.” ............................. 35 
`
`Ehses-Dissertation Anticipates Claims 2-4 ............................... 36 
`
`Ehses-Dissertation Anticipates Claims 5-6, 8, and 10-11 ........ 36 
`
`Ehses-Dissertation Anticipates Claims 12-13 .......................... 37 
`
`Ehses-Dissertation Anticipates Claims 15-16 .......................... 38 
`
`Ehses-Dissertation Anticipates Claim 18 ................................. 38 
`
`Ehses-Dissertation Anticipates Claim 19 ................................. 38 
`
`Ehses-Dissertation Anticipates Claim 20 ................................. 39 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
`
`10.  Ehses-Dissertation Anticipates Claim 21 ................................. 39 
`
`11.  Ehses-Dissertation Anticipates Claim 22 ................................. 39 
`
`12.  Ehses-Dissertation Anticipates Claim 23 ................................. 40 
`
`13.  Ehses-Dissertation Anticipates Claims 24-34 .......................... 41 
`
`14.  Ehses-Dissertation Anticipates Claim 35 ................................. 42 
`
`G. 
`
`Claims 1-6, 8, 10-13, 15-16, and 18-35 Are Rendered Obvious
`by Ehses and Ehses-Dissertation ........................................................ 42 
`
`
`
`v
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`H. 
`
`Claims 1-8, 10-17, 19, and 22-35 Are Anticipated by
`Piepenburg .......................................................................................... 44 
`
`1. 
`
`2. 
`
`The Teachings of Piepenburg ................................................... 44 
`
`Piepenburg Anticipates Claim 1 ............................................... 46 
`
`a. 
`
`b. 
`
`c. 
`
`d. 
`
`e. 
`
`f. 
`
`g. 
`
`“A method of amplifying a target polynucleotide
`sequence, the method comprising…” ............................. 46 
`
`“…obtaining from an animal, plant or food, a sample
`comprising a target nucleic acid, the target nucleic acid
`comprising the target polynucleotide sequence…” ........ 46 
`
`“…without first subjecting the target nucleic acid to a
`thermal denaturation step associated with amplification
`of the target polynucleotide sequence…” ....................... 47 
`
`“…combining in a single step, the obtained sample
`directly with an amplification reagent mixture or diluting
`the obtained sample and combining, in a single step, the
`diluted sample with an amplification reagent mixture, …
`the amplification reagent mixture being free of bumper
`primers…”” ..................................................................... 48 
`
`“…and comprising: (i) a polymerase…” ........................ 48 
`
`“… (ii) a nicking enzyme…” .......................................... 49 
`
`“… (iii) a first oligonucleotide comprising a 5′ portion
`that comprises a nicking enzyme binding site that is non-
`complementary to the target polynucleotide sequence and
`a 3′ portion that hybridizes to the target polynucleotide
`sequence, and (iv) a secon oligonucleotide comprising a
`5′ portion that comprises a nicking enzyme binding site
`that is non-complementary to the target polynucleotide
`sequence and a 3′ portion that hybridizes to the target
`polynucleotide sequence……” ....................................... 49 
`
`h. 
`
`“…subjecting the reaction mixture formed by the step of
`combining to essentially isothermal conditions to amplify
`
`
`
`vi
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`the target polynucleotide sequence without the assistance
`of bumper primers …” .................................................... 51 
`
`i. 
`
`j. 
`
`“…detecting the amplified target polynucleotide
`sequence in real time…” ................................................. 51 
`
`“…within 10 minutes of subjecting the reaction mixture
`to essentially isothermal conditions.” ............................. 52 
`
`Piepenburg Anticipates Claims 2-4 .......................................... 52 
`
`Piepenburg Anticipates Claims 5-8 and 10-11 ......................... 53 
`
`Piepenburg Anticipates Claims 12-17 ...................................... 55 
`
`Piepenburg Anticipates Claim 19 ............................................. 55 
`
`Piepenburg Anticipates Claim 22 ............................................. 56 
`
`Piepenburg Anticipates Claim 23 ............................................. 56 
`
`Piepenburg Anticipates Claims 24-35 ...................................... 56 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
`
`I. 
`
`Claim 18 Is Rendered Obvious by Piepenburg in view of Kong ....... 57 
`
`1. 
`
`2. 
`
`The Teachings of Kong ............................................................. 57 
`
`Piepenburg in view of Kong renders obvious Claim 18 ........... 57 
`
`J. 
`
`Claim 20 Is Rendered Obvious by Piepenburg in view of Kato ........ 58 
`
`1. 
`
`2. 
`
`The Teachings of Kato .............................................................. 58 
`
`Piepenburg in view of Kato renders obvious Claim 20 ............ 59 
`
`Claims 1-8 and 10-35 Are Rendered Obvious by Piepenburg in
`view of Ehses and Ehses-Dissertation ................................................ 59 
`
`Claims 1-8 and 10-35 Are Rendered Obvious by Ehses and
`Ehses-Dissertation in view of Piepenburg ......................................... 60 
`
`K. 
`
`L. 
`
`IV.  CONCLUSION .............................................................................................. 61 
`
`
`
`
`
`vii
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`Attachment A. Proof of Service of the Petition
`
`Attachment B. List of Evidence and Exhibits Relied Upon in Petition
`
`
`
`
`
`
`
`viii
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`In re Montgomery,
`
`677 F.3d 1375, 1379 (Fed. Cir. 2012) ................................................................ 22
`
`In re Slayter,
`
`276 F.2d 408, 411, 125 USPQ 345, 347 (CCPA 1960) ................................ 26, 38
`
`In re Gosteli,
`
`872 F.2d 1008, 10 USPQ2d 1614 (Fed. Cir. 1989) ...................................... 26, 38
`
`Titanium Metals Corp. v. Banner,
`
`778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) .................................................. 27
`
`Eli Lilly & Co. v. Zenith Goldline Pharm., Inc.,
`
`471 F.3d 1369, 1376 (Fed. Cir. 2006) ................................................................ 37
`
`In re Petering,
`
`301 F.2d 676, 133 USPQ 275 (CCPA 1962) ...................................................... 54
`
` Kennametal Inc. v. Ingersoll Cutting Tool Co.,
`
`780 F.3d 1376 (Fed. Cir. 2015) .......................................................................... 54
`
`
`
`
`
`
`
`
`ix
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`I.
`
`Compliance with Requirements of Inter Partes Review Petition
`A. Certification that the Patent May Be Contested via Inter Partes
`Review by the Petitioner (37 CFR §§ 42.101 and 42.104)
`Petitioner certifies that U.S. Patent No. 9,562,263 (“the ‘263 patent”) [Ex.
`
`1001]) is available for review and that Petitioner is not barred or estopped from
`
`requesting inter partes review of the claims of the ‘263 patent. Neither Petitioner,
`
`nor Petitioner’s real party in interest, nor any privy of Petitioner: (a) has filed a
`
`civil action challenging the validity of the claims of the ‘263 patent; (b) has been
`
`served a complaint alleging infringement of the ‘263 patent more than a year prior
`
`to the present date; or (c) is estopped from challenging the claims of the ‘263
`
`patent.
`
`Fee for Inter Partes Review (37 CFR § 42.15(a))
`
`B.
`The Director is authorized to charge the fee specified by 37 CFR §42.15(a)
`
`to Deposit Account No. 50-2678, which fee is believed to be $23,000. Any
`
`necessary additional fees may be charged to Deposit Account No. 50-2678.
`
`C. Mandatory Notices (37 CFR § 42.8(b))
`1.
`Real Party in Interest (37 CFR § 42.8(b)(1))
`The real party of interest of this petition is EnviroLogix Inc., a U.S.
`
`company at the address of 500 Riverside Industrial Parkway, Portland, ME 04103
`
`(“Petitioner”). No other entity is a real party of interest or a privy for purposes of
`
`this petition.
`
`
`
`1
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`Other Proceedings (37 CFR § 42.8(b)(2))
`
`2.
`To Petitioner’s knowledge, the ‘263 patent is not presently the subject of
`
`other proceedings. Ionian Technologies, Inc. (“Ionian”) is the owner of the
`
`following U.S. applications and patents that are related to the ‘263 patent: Appl.
`
`No. 14/067,623, now U.S. Patent No. 9,562,264; Appl. No. 14/067,623, now U.S.
`
`Patent No. 9,617,586; and Appl. No. 11/778,018, now U.S. Patent No. 9,689,031.
`
`Petitioner reserves the right to petition for inter partes review of U.S. Patent Nos.
`
`9,562,264, 9,617,586 and 9,689,031.
`
`3.
`
`Lead and Backup Lead Counsel (37 CFR § 42.8(b)(3))
`
`Lead Counsel
`Jonathan D. Ball, Ph.D.
`Registration No. 59,928
`GREENBERG TRAURIG, LLP
`Met Life Building
`200 Park Avenue, 38th Floor
`New York, New York 10166
`ballj@gtlaw.com
`Phone: (212) 801-2223
`Fax: (212) 801-6400
`
`Backup Lead Counsel
`Melissa Hunter-Ensor, Ph.D.
`Registration No. 55,289
`GREENBERG TRAURIG, LLP
`One International Place, Suite 2000
`Boston, MA 02110
`hunterensorm@gtlaw.com
`Phone: (617) 310-6224
`Fax: (617) 310-6001
`
`Service Information (37 CFR § 42.8(b)(4))
`
`4.
`Service on Petitioner may be made by mail or hand delivery to: Greenberg
`
`
`
`Traurig, LLP, One International Place, Suite 2000, Boston, MA 02110. Petitioner
`
`also consents to service by email to: bosipmail@gtlaw.com.
`
`Proof of Service (37 CFR §§ 42.6(e) and 42.105(a))
`
`D.
`Proof of service of this petition is provided in Attachment A.
`
` 2
`
`
`
`
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`II.
`
`Identification of Claims Being Challenged (37 CFR § 42.104(b))
`
`Claims 1-8 and 10-35 of the ‘263 patent are unpatentable for the following
`
`reasons:
`
` Claims 1-6, 8, 10-13, 15-16, and 18-35 are anticipated under 35 U.S.C. §102
`
`(pre-AIA) by Ehses et al. J Biochem Biophys Methods. 2005 Jun
`
`30;63(3):170-86 (hereafter, “Ehses”) [Ex. 1002].
`
` Claims 1-6, 8, 10-13, 15-16, and 18-35 are anticipated under 35 U.S.C. §102
`
`(pre-AIA) by Ehses, S., Isothermale in vitro Selektion und Amplifikation zur
`
`Untersuchung von Evolutionsvorgängen (Dissertation, August 2005, Ruhr-
`
`Universität Bochum) (hereafter, “Ehses-Dissertation”) [Ex. 1003]. A
`
`certified English translation of Ehses is provided (hereafter, “Ehses-
`
`Translation”) [Ex. 1004].
`
` Claims 1-6, 8, 10-13, 15-16, 18-35 are obvious under 35 U.S.C. §103 (pre-
`
`AIA) over Ehses and Ehses-Dissertation.
`
` Claims 1-8, 10-17, 19, and 22-35 are anticipated under 35 U.S.C. §102 (pre-
`
`AIA) by U.S. Publication No. 2005/0112631 to Piepenburg et al. (hereafter,
`
`“Piepenburg”) [Ex. 1005].
`
` Claims 18 is obvious under 35 U.S.C. §103 (pre-AIA) over Piepenburg in
`
`view of PCT Publication No. WO2001/094544 to Kong et al. (hereafter,
`
` 3
`
`
`
`“Kong”) [Ex. 1006].
`
`
`
`

`

`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
` Claim 20 is obvious under 35 U.S.C. §103 (pre-AIA) over Piepenburg in
`
`view of Kato et al., Eur J Biochem. 1999 Feb;259(3):592-601 (hereafter,
`
`“Kato”) [Ex. 1007].
`
` Claims 1-8 and 10-35 are obvious under 35 U.S.C. §103 (pre-AIA) over
`
`Piepenburg in view of Ehses and Ehses-Dissertation.
`
` Claims 1-8 and 10-35 are obvious under 35 U.S.C. §103 (pre-AIA) over
`
`Ehses and Ehses-Dissertation in view of Piepenburg.
`
`Ehses, Ehses-Dissertation, Piepenburg, Kong, and Kato each constitutes
`
`prior art to the ‘263 patent under 35 U.S.C. §102(b) (pre-AIA) because each was
`
`published more than one year prior to the earliest claimed priority date of the ‘263
`
`patent.
`
`A list of evidence relied upon in support of this petition is provided in
`
`Attachment B.
`
`A Declaration of Jeremy Edwards, Ph.D. regarding the invalidity of the ‘263
`
`patent (“Edwards-Decl.”), along with his CV and materials relied on and
`
`considered are included herewith as [Ex. 1008]. Dr. Edwards is a Professor of
`
`Chemistry and Chemical Biology, Internal Medicine, Molecular Genetics, and
`
`Microbiology at the University of New Mexico School of Medicine. Dr. Edwards
`
`specializes in high-throughput DNA sequencing, genomics, and DNA technology.
`
`Petitioner’s proposed claim constructions, evidence relied upon, and precise
`
` 4
`
`
`
`
`
`

`

`reasons why the claims are unpatentable, are shown below in Section III.
`
`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
`
`
`III. Relevant Information Concerning the Contested Patent
`A.
`Person of Ordinary Skill in the Art
`A person of ordinary skill in the art ("POSA") is a hypothetical person who
`
`is aware of pertinent art, including from the scientific, technical, and/or patent
`
`literature; thinks along lines of conventional wisdom; and possesses ordinary
`
`creativity. In this case, a POSA has knowledge of molecular biology, a Ph.D. in
`
`molecular biology, and experience in nucleic acid amplification techniques,
`
`detection, and analysis.
`
`B.
`
`Prosecution History of the ‘263 Patent and Explanation under
`Sec. 325(d)
`
`The primary prior art references (“the References”) at issue in this Petition
`
`are Ehses, Ehses-Dissertation, and Piepenburg. Ehses was cited by Applicant in an
`
`Information Disclosure Statement filed August 11, 2016, but never served as the
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`basis for any rejection. Ehses-Dissertation was never cited. U.S. Patent No.
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`7,399,590, corresponding to Piepenburg, was cited by Applicant in an Information
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`Disclosure Statement filed January 9, 2015, but never served as the basis for any
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`rejection.
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`It is clear that the Examiner did not apprehend the full disclosures of the
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`References because as detailed below the References clearly should have been
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`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
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`cited in an anticipation or obviousness rejection. A copy of the file history of the
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`‘263 patent is included herewith as [Ex. 1009]. In order to secure patentability, the
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`claims of the ‘263 patent were amended to recite:
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` without ...subjecting the target nucleic acid to a thermal denaturation
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`step. See January 9, 2015 Response-to-Office-Action, p. 2, and July
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`27, 2015 Response-to-Office-Action, p. 2;
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` combining in a single step…with an amplification reagent mixture.
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`See September 2, 2016 Response-to-Office-Action, p. 2;
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` subjecting the reaction mixture ...to essentially isothermal conditions
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`to amplify the target ...without the assistance of bumper primers. See
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`September 2, 2016 Response-to-Office-Action, p. 2; and
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` detecting the amplified target polynucleotide sequence in real time
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`within 10 minutes. See September 2, 2016 Response-to-Office-
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`Action, p. 3.
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`The amendment of the claims to include these limitations allowed the Patent
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`Owner to distinguish over the prior art applied by the Examiner during
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`prosecution. As discussed herein below, these claim limitations are disclosed in
`
`the References, but there is no evidence indicating that the Examiner appreciated
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`this fact. Thus, the References present new issues that were not considered by the
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`Office during prosecution.
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`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
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`C. Construction of Terms Used in the Claims
`The earliest claimed priority date of the ‘263 patent is July 14, 2007, and
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`therefore it has an apparent expiration date of July 14, 2027. As such, the
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`“broadest reasonable construction” standard of 37 C.F.R. § 42.100(b) is applicable.
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`General Observations
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`1.
`Petitioner sets forth below preliminary claim constructions pertinent to
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`validity. The following remarks apply to all of the claim constructions provided
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`below. The claims are construed under the “broadest reasonable construction”
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`standard. Where a term below is not defined in the ‘263 patent, the term carries its
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`plain-and-ordinary meaning to a POSA. Petitioner reserves the right to amend any
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`of the constructions below in any litigation concerning the ‘263 patent, as
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`discovery and expert testimony may shed light on how these terms would have
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`been understood by a POSA. Furthermore, by offering these constructions,
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`Petitioner does not concede that any of the specific terms construed below, or other
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`terms in the claims, are definite. To the contrary, Petitioner believes that many of
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`the terms are indefinite and reserves all rights to argue indefiniteness in litigation.
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`Petitioner submits the following constructions for purposes of this Petition only.
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`2.
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`Constructions
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`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
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`“a sample comprising a target nucleic acid”
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`a.
`The ‘263 patent does not define “a sample [from an animal, plant or food]
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`comprising a target nucleic acid.” A POSA understands that “a sample” is any
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`representative portion of an animal, plant, or food that contains a polynucleotide.
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`See Edwards-Decl. ¶34.
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`Dependent claim 15 specifies that the target nucleic acid (“Target”) can be
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`“synthetic double-stranded DNA and synthetic single-stranded DNA.” Thus, the
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`“target nucleic acid” of Claim 1 embraces multiple types of polynucleotides.
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`Because Claim 15 recites synthetic polynucleotides, under the doctrine of claim
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`differentiation, the term “sample” is not limited to samples that occur in nature.
`
`b.
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`“a thermal denaturation step associated with amplification
`of the target polynucleotide sequence”
`
`The ‘263 patent does not define a “thermal denaturation step associated with
`
`amplification of the target polynucleotide sequence” and does not provide
`
`guidance to determine whether a thermal denaturation step is “associated with
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`amplification of the target polynucleotide sequence.” See Edwards Decl. ¶36.
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`“A thermal denaturation step associated with amplification of the target
`
`polynucleotide sequence” is understood to be a heating step that denatures the
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`Target, thereby facilitating an amplification reaction (AmpRxn). See Edwards-
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`Decl. ¶37. This construction is consistent with the ‘263 patent which states: “An
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`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
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`initial heat denaturation step is not required for the methods of the present
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`invention.” See col. 3, lns. 52-53. This is in contrast to other AmpRxns, e.g.,
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`Strand Displacement Amplification (SDA), which “requires an initial heat
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`denaturation step for double-stranded targets.” See col. 3, lns. 13-14.
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` “combining, in a single step, …”
`
`c.
`The ‘263 patent does not define “combining, in a single step.” The claims
`
`provide for “combining [the sample] in a single step directly” and “diluting [the
`
`sample] and combining [the sample] in a single step.” Where the combining step
`
`recites “directly,” a POSA understands that the sample has not been altered from
`
`the form in which it occurs. See Edwards-Decl. ¶40. Where the combining step
`
`recites “diluting the obtained sample,” a POSA understands that the sample has
`
`been diluted, but not otherwise altered. See Edwards-Decl. ¶40.
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`“bumper primers”
`
`d.
`The ‘263 patent does not define “bumper primers.” Regarding SDA, such
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`reactions include a pair of primers that bind to and amplify a Target. In contrast,
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`“bumper primers” refers to an additional set of “oligonucleotides that bind outside
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`the target region and, when extended, displace a single strand of a double-stranded
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`nucleic acid molecule.” See Edwards-Decl. ¶42. As such, the term “bumper
`
`primers” does not encompass amplification primers. See Edwards-Decl. ¶42.
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`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
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`
` “polymerase”
`
`e.
`The ‘263 patent uses “polymerase” to mean “a protein able to catalyze the
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`specific incorporation of nucleotides to extend a 3′ hydroxyl terminus of a primer
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`molecule.” See col. 3, lns. 6-8. Examples of polymerases are provided at Table 1,
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`including Bst DNA polymerase and Bst DNA polymerase (Large fragment). See
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`col. 14, lns. 28-63.
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`“nicking enzyme”
`
`f.
`The ‘263 patent uses “nicking enzyme” to mean “a protein that binds to
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`double-stranded DNA and cleaves one strand of a double-stranded duplex.” See
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`col. 15, lns. 5-7. Examples of nicking enzymes are provided at Table 2, including
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`Nt.BstNBI, Nb.BbvCi, and Nt.BbvCI. See col. 15, lns. 25-54.
`
`g.
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`“oligonucleotide comprising a 5′ portion that comprises a
`nicking enzyme binding site that is non-complementary to
`the target polynucleotide sequence and a 3′ portion that
`hybridizes to the target polynucleotide sequence”
`
`The ‘263 patent does not define “oligonucleotide comprising a 5′ portion
`
`that comprises a nicking enzyme binding site that is non-complementary to the
`
`target polynucleotide sequence and a 3′ portion that hybridizes to the target
`
`polynucleotide sequence.” However, a POSA will recognize that oligonucleotides
`
`having the recited structures function as primers, in that they bind a Target strand
`
`and generate a complementary strand by polymerase extension. See Edwards-
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`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
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`Decl. ¶45. The presence of a nicking enzyme binding site allows nicking and
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`extension of the oligonucleotide. See Edwards-Decl. ¶45.
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`“amplification reagent mixture”
`
`h.
`The ‘263 patent does not define an “amplification reagent mixture.” A
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`
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`POSA understands an “amplification reagent mixture” to mean a composition
`
`comprising a polymerase, a nicking enzyme, and a pair of primers for amplifying a
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`Target. See Edwards-Decl. ¶47. This is consistent with its use in the claims,
`
`which recite:
`
`…the amplification reagent mixture... comprising: (i) a polymerase,
`(ii) a nicking enzyme, (iii) a first oligonucleotide... and (iv) a second
`oligonucleotide...
`
`The term “amplification reagent mixture” is open-ended. Thus, the amplification
`
`reagent mixture may comprise additional components.
`
`“essentially isothermal conditions”
`
`i.
`The ‘263 patent defines “isothermal conditions” as “a set of reaction
`
`
`
`conditions where the temperature of the reaction is kept essentially constant
`
`during the reaction.” See col. 16, lns. 23-26. The term “essentially” as it
`
`applies to isothermal conditions is not defined. However, the specification
`
`indicates:
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`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
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`[I]t is not necessary that the temperature be maintained at precisely
`one temperature. If the equipment used to maintain an elevated
`temperature allows the temperature of the reaction mixture to vary by
`a few degrees, this is not detrimental to the amplification reaction, and
`may still be considered to be an isothermal reaction. See col. 16, lns.
`29-37.
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`“real time”
`
`j.
`The ‘263 patent does not