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`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
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`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: July 14, 2007
`Inventor: Maples et al.
`Title: NICKING AND EXTENSION AMPLIFICATION REACTION FOR THE
`EXPONENTIAL AMPLIFICATION OF NUCLEIC ACIDS
`
`______________________
`
`
`
`Inter Partes Review No. 2018-00405
`
`
`
`DECLARATION OF DR. JEREMY EDWARDS
`
`
`
`1
`
`ELIX 1008
`
`

`

`Declaration of Dr. Jeremy Edwards
`
`
`TABLE OF CONTENTS
`
`I, Dr. Jeremy Edwards, hereby declare as follows: ................................................... 2 
`
`I. 
`
`Introduction ...................................................................................................... 2 
`
`A. 
`
`Background and Qualifications ............................................................ 2 
`
`B.  Materials Considered ............................................................................ 3 
`
`C. 
`
`Summary of Opinions ........................................................................... 3 
`
`II. 
`
`Legal Standards for Patentability ..................................................................... 5 
`
`A.  Anticipation .......................................................................................... 6 
`
`B. 
`
`Obviousness .......................................................................................... 7 
`
`III. 
`
`Person of Ordinary Skill in the Art .................................................................. 9 
`
`IV.  The ‘263 Patent .............................................................................................. 10 
`
`A. 
`
`B. 
`
`C. 
`
`Brief Technical Overview of the ‘263 Patent .................................... 10 
`
`Prosecution History of the ‘263 Patent .............................................. 11 
`
`Construction of Terms Used in the Claims ........................................ 12 
`
`a. 
`
`b. 
`
`c. 
`
`d. 
`
`e. 
`
`f. 
`
`g. 
`
`“a sample comprising a target nucleic acid” .................. 13 
`
`“a thermal denaturation step associated with
`amplification of the target polynucleotide sequence” .... 13 
`
`“ combining, in a single step, …” ................................... 15 
`
`“bumper primers” ........................................................... 15 
`
`“polymerase” .................................................................. 16 
`
`“nicking enzyme” ........................................................... 16 
`
`“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” ......... 17 
`i
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`2
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`Declaration of Dr. Jeremy Edwards
`
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`h. 
`
`i. 
`
`j. 
`
`k. 
`
`l. 
`
`“amplification reagent mixture” ..................................... 17 
`
`“essentially isothermal conditions” ................................ 19 
`
`“real time” ....................................................................... 19 
`
`“duplex” .......................................................................... 21 
`
`“extending” ..................................................................... 22 
`
`m. 
`
`“genomic DNA” ............................................................. 22 
`
`D. 
`
`Effective Filing Date of the ‘263 Patent ............................................ 23 
`
`V. 
`
`Patentability Evaluation of the ‘263 Patent ................................................... 23 
`
`A. 
`
`Claims 1-6, 8, 10-13, 15-16, and 18-35 Are Anticipated by
`Ehses ................................................................................................... 23 
`
`1. 
`
`2. 
`
`The Teachings of Ehses ............................................................ 24 
`
`Ehses Anticipates Claim 1 ........................................................ 25 
`
`a. 
`
`b. 
`
`c. 
`
`d. 
`
`e. 
`
`f. 
`
`“A method of amplifying a target polynucleotide
`sequence, the method comprising …” ............................ 26 
`
`“…obtaining from an animal, plant or food, a sample
`comprising a target nucleic acid, the target nucleic acid
`comprising the target polynucleotide sequence …” ....... 27 
`
`“…without first subjecting the target nucleic acid to a
`thermal denaturation step associated with amplification
`of the target polynucleotide sequence…” ....................... 28 
`
`“…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…” ...................................................................... 28 
`
`“…and comprising: (i) a polymerase…” ....................... 29 
`
`“…(ii) a nicking enzyme …” .......................................... 30 
`ii
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`Declaration of Dr. Jeremy Edwards
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`“… (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, …” ......................................... 30 
`
`“… 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…” ..................................................... 32 
`
`“…detecting the amplified target polynucleotide
`sequence in real time...” .................................................. 33 
`
`“…within 10 minutes of subjecting the reaction mixture
`to essentially isothermal conditions.” ............................. 34 
`
`g. 
`
`h. 
`
`i. 
`
`j. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
`
`Ehses Anticipates Claims 2-4 ................................................... 35 
`
`Ehses Anticipates Claims 5-6, 8, and 10-11 ............................. 38 
`
`Ehses Anticipates Claims 12-13 ............................................... 39 
`
`Ehses Anticipates Claims 15-16 ............................................... 40 
`
`Ehses Anticipates Claim 18 ...................................................... 40 
`
`Ehses Anticipates Claim 19 ...................................................... 41 
`
`Ehses Anticipates Claim 20 ...................................................... 41 
`
`10.  Ehses Anticipates Claim 21 ...................................................... 42 
`
`11.  Ehses Anticipates Claim 22 ...................................................... 43 
`
`12.  Ehses Anticipates Claim 23 ...................................................... 44 
`
`13.  Ehses Anticipates Claims 24-34 ............................................... 46 
`
`14.  Ehses Anticipates Claim 35 ...................................................... 48 
`iii
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`Declaration of Dr. Jeremy Edwards
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`B. 
`
`Claims 1-6, 8, 10-13, 15-16, and 18-35 Are Anticipated by
`Ehses-Dissertation .............................................................................. 50 
`
`1. 
`
`2. 
`
`The Teachings of Ehses-Dissertation ....................................... 50 
`
`Ehses-Dissertation Anticipates Claim 1 ................................... 52 
`
`a. 
`
`b. 
`
`c. 
`
`d. 
`
`e. 
`
`f. 
`
`g. 
`
`“A method of amplifying a target polynucleotide
`sequence, the method comprising …” ............................ 52 
`
`“…obtaining from an animal, plant or food, a sample
`comprising a target nucleic acid, the target nucleic acid
`comprising the target polynucleotide sequence …” ....... 52 
`
`“…without first subjecting the target nucleic acid to a
`thermal denaturation step associated with amplification
`of the target polynucleotide sequence…” ....................... 53 
`
`“…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 …” ..................................................................... 54 
`
`“…and comprising: (i) a polymerase…” ....................... 55 
`
`“…(ii) a nicking enzyme …” .......................................... 55 
`
`“… (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 …” .......................................... 56 
`
`h. 
`
`“… subjecting the reaction mixture formed by the step of
`combining to essentially isothermal conditions to amplify
`
`
`
`iv
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`5
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`Declaration of Dr. Jeremy Edwards
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`
`the target polynucleotide sequence without the assistance
`of bumper primers …” .................................................... 58 
`
`i. 
`
`j. 
`
`“…detecting the amplified target polynucleotide
`sequence in real time...” .................................................. 59 
`
`“…within 10 minutes of subjecting the reaction mixture
`to essentially isothermal conditions.” ............................. 60 
`
`Ehses-Dissertation Anticipates Claims 2-4 ............................... 61 
`
`Ehses-Dissertation Anticipates Claims 5-6, 8, and 10-11 ........ 62 
`
`Ehses-Dissertation Anticipates Claims 12-13 .......................... 63 
`
`Ehses-Dissertation Anticipates Claims 15-16 .......................... 64 
`
`Ehses-Dissertation Anticipates Claim 18 ................................. 64 
`
`Ehses-Dissertation Anticipates Claim 19 ................................. 64 
`
`Ehses-Dissertation Anticipates Claim 20 ................................. 65 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
`
`10.  Ehses-Dissertation Anticipates Claim 21 ................................. 65 
`
`11.  Ehses-Dissertation Anticipates Claim 22 ................................. 66 
`
`12.  Ehses-Dissertation Anticipates Claim 23 ................................. 67 
`
`13.  Ehses-Dissertation Anticipates Claims 24-34 .......................... 68 
`
`14.  Ehses-Dissertation Anticipates Claim 35 ................................. 69 
`
`C. 
`
`Claims 1-6, 8, 10-17, and 19-35 Are Rendered Obvious by
`Ehses and Ehses-Dissertation ............................................................. 69 
`
`1. 
`
`Ehses and Ehses-Dissertation render obvious Claims 1-6,
`8, 10-13, 15-16, and 18-35 ........................................................ 69 
`
`D. 
`
`Claims 1-8, 10-17, 19, and 22-35 Are Anticipated by
`Piepenburg .......................................................................................... 71 
`
`1. 
`
`2. 
`
`The Teachings of Piepenburg ................................................... 71 
`
`Piepenburg Anticipates Claim 1 ............................................... 74 
`v
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`6
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`

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`Declaration of Dr. Jeremy Edwards
`
`
`“A method of amplifying a target polynucleotide
`sequence, the method comprising …” ............................ 74 
`
`“…obtaining from an animal, plant or food, a sample
`comprising a target nucleic acid, the target nucleic acid
`comprising the target polynucleotide sequence …” ....... 74 
`
`“…without first subjecting the target nucleic acid to a
`thermal denaturation step associated with amplification
`of the target polynucleotide sequence…” ....................... 75 
`
`“…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…”
` ........................................................................................ 76 
`
`“…the amplification reagent mixture being free of
`bumper primers …” ........................................................ 77 
`
`“…and comprising: (i) a polymerase…” ....................... 78 
`
`“…(ii) a nicking enzyme …” .......................................... 78 
`
`“… (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, …” ......................................... 79 
`
`“… 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 …” .................................................... 81 
`
`“…detecting the amplified target polynucleotide
`sequence in real time...” .................................................. 82 
`
`a. 
`
`b. 
`
`c. 
`
`d. 
`
`e. 
`
`f. 
`
`g. 
`
`h. 
`
`i. 
`
`j. 
`
`
`
`vi
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`7
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`Declaration of Dr. Jeremy Edwards
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`k. 
`
`“…within 10 minutes of subjecting the reaction mixture
`to essentially isothermal conditions.” ............................. 82 
`
`Piepenburg Anticipates Claims 2-4 .......................................... 83 
`
`Piepenburg Anticipates Claims 5-8 and 10-11 ......................... 84 
`
`Piepenburg Anticipates Claims 12-17 ...................................... 85 
`
`Piepenburg Anticipates Claim 19 ............................................. 86 
`
`Piepenburg Anticipates Claim 22 ............................................. 86 
`
`Piepenburg Anticipates Claim 23 ............................................. 87 
`
`Piepenburg Anticipates Claims 24-35 ...................................... 87 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
`
`E. 
`
`Claims 18 and 21 Are Rendered Obvious by Piepenburg in
`view of Kong ...................................................................................... 88 
`
`1. 
`
`2. 
`
`The Teachings of Kong ............................................................. 88 
`
`Piepenburg in view of Kong renders obvious Claim 18 ........... 88 
`
`F. 
`
`Claim 20 Is Rendered Obvious by Piepenburg in view of Kato ........ 89 
`
`1. 
`
`2. 
`
`The Teachings of Kato .............................................................. 90 
`
`Piepenburg in view of Kato renders obvious Claim 20 ............ 90 
`
`Claims 1-8 and 10-35 Are Rendered Obvious by Piepenburg in
`view of Ehses and Ehses-Dissertation ................................................ 90 
`
`Claims 1-8 and 10-35 Are Rendered Obvious by Ehses and
`Ehses-Dissertation in view of Piepenburg ......................................... 91 
`
`G. 
`
`H. 
`
`VI.  CONCLUSION .............................................................................................. 92 
`
`
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`Attachment A. CV of Dr. Jeremy Edwards
`
`Attachment B. List of Evidence and Exhibits Relied Upon in Petition
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`vii
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`Petition re U.S. Pat. No. 9,562,263 (Claims 1-8 and 10-35)
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`I, Dr. Jeremy Edwards, do hereby declare and state that all statements made
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`herein of my own knowledge are true and that all statements made on information
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`and belief are believed to be true; and further that these statements were made with
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`the knowledge that willful false statements and the like so made are punishable by
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`fine, or imprisonment, or both under Section 1001 of Title 18 of the United States
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`Code.
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`Dated December 27, 2017
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`______________________
`
`Dr. Jeremy Edwards
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`
`
`1
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`9
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`

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`Declaration of Dr. Jeremy Edwards
`
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`I, Dr. Jeremy Edwards, hereby declare as follows:
`
`I.
`
`Introduction
`1.
`
`I have been retained by Greenberg Traurig, LLP, on behalf of
`
`EnviroLogix Inc. (“EnviroLogix”), as an expert in the above-captioned
`
`proceeding. I have been asked to render an opinion regarding the validity of
`
`claims 1-35 of U.S. Patent No. 9,562,263 (“the ‘263 patent”). [Ex. 1001].
`
`2.
`
`I am being compensated at a rate of up to $500 per hour for my study
`
`and testimony in this matter. I am also being reimbursed for my reasonable and
`
`customary expenses associated with my work and testimony in this matter. My
`
`compensation is not contingent on the outcome of this matter or the specifics of
`
`my testimony.
`
`3.
`
`Between 2009 and 2013, I have been retained as an expert in Life
`
`Technologies Corporation v. Illumina Inc., 3:11-cv-00703-CaB-DHB, 2012 WL
`
`4003429 (S.D. Cal. 2012). I provided expertise on technology for the surface
`
`amplification of DNA molecules.
`
`A. Background and Qualifications
`
`4.
`
`I am a Professor of Chemistry and Chemical Biology, Internal
`
`Medicine, Molecular Genetics, and Microbiology at the University of New
`
`Mexico School of Medicine. I specialize in high-throughput DNA sequencing,
`
` 2
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`
`10
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`

`

`Declaration of Dr. Jeremy Edwards
`
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`genomics, and DNA technology. Over the past 22 years, my research has
`
`covered multiple aspects of DNA amplification. Notably, I have developed
`
`amplification strategies for Next Generation Sequencing technology, such as,
`
`emulsion PCR and isothermal rolling circle amplification.
`
`5.
`
`A copy of my curriculum vitae outlining my full professional and
`
`educational experiences and additional relevant qualifications is attached to this
`
`declaration as Attachment A.
`
`B. Materials Considered
`
`6.
`
`In forming my opinions, in addition to my knowledge and expertise, I
`
`have considered the materials listed in Attachment B, as well as any materials
`
`cited herein that may not be listed.
`
`C.
`
`7.
`
`Summary of Opinions
`
`For ease of reference, I provide below a summary of the reasons
`
`(discussed more fully below) for my opinion that claims 1-8 and 10-35 of the ‘263
`
`patent are unpatentable:
`
` 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].
`
` 1-6, 8, 10-13, 15-16, 18-35 are anticipated under 35 U.S.C. §102 (pre-
`
`AIA) by Ehses, S., Isothermale in vitro Selektion und Amplifikation
`
` 3
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`
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`
`
`11
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`

`

`Declaration of Dr. Jeremy Edwards
`
`
`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, “Kong”) [Ex. 1006].
`
` 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.
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` 4
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`12
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`

`

`Declaration of Dr. Jeremy Edwards
`
`
`8.
`
`I understand that each of Ehses, Ehses-Dissertation, Piepenburg,
`
`Kong, and Kato constitutes prior art 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 claims 1-8 and 10-35.
`
`
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`II. Legal Standards for Patentability
`9.
`In forming my opinion detailed herein, I am relying on certain legal
`
`principles that counsel has explained to me.
`
`10.
`
`I understand that, for an invention claimed in a patent to be found
`
`patentable, it must at least be novel and not obvious over patents and other
`
`publications that predate it. I understand that the patents and other publications
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`that predate the invention are referred to as "prior art."
`
`11.
`
`I understand that, in this matter, the burden is on the party asserting
`
`unpatentability to prove it by a preponderance of the evidence. I understand that
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`“a preponderance of the evidence” is evidence sufficient to show that a fact is
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`more likely true than not true.
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`12.
`
`I understand that the unpatentability analysis requires that the claims
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`first be construed. After the claims are construed, they are then compared to the
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`prior art.
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`13.
`
`I understand that the ‘263 patent has an apparent expiration date of
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` 5
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`13
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`

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`Declaration of Dr. Jeremy Edwards
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`November 12, 2026, and that the “broadest reasonable construction” standard is
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`applicable. That is, the claim construction should be made pursuant to the
`
`principle that claim terms are generally given their broadest reasonable
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`interpretation in view of the specification to one having ordinary skill in the art at
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`the time of the invention. I further understand that the patentee also can be their
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`own lexicographer either by providing an explicit definition of a term, or defining
`
`a term implicitly through the usage of the term in the specification.
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`14.
`
`I understand that, in this matter, the prior art is limited to patents and
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`printed publications. My analysis below compares the claims as interpreted to
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`patents and printed publications that are prior art to the claims of the '263 patent.
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`Counsel has explained that there are two ways in which prior art may render a
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`patent claim unpatentable. First, the prior art can be shown to “anticipate” the
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`claim. Second, the prior art can be shown to “render obvious” the claim. My
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`understanding of the two legal standards as explained to me by counsel is set forth
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`below.
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`A. Anticipation
`15.
`I understand that, for a patent claim to be “anticipated” by the prior
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`art, each and every element of the claim must be found, expressly or inherently, in
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`a single prior art reference. I have applied this standard in my evaluation of
`
`whether the claims of the '263 patent are anticipated.
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`14
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`Declaration of Dr. Jeremy Edwards
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`16.
`
`I understand that, for a claim element to be found inherently in a prior
`
`art reference, the inherent element necessarily must be present if the teachings of
`
`the prior art are followed. I also understand that inherency cannot be established
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`by probabilities or possibilities, and the mere fact that something may result from a
`
`given set of circumstances is not sufficient to show inherency.
`
`B. Obviousness
`17.
`I understand that the following standards govern the determination of
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`whether a claim in a patent is obvious. I have applied these standards in my
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`evaluation of whether the claims of the '263 patent would have been considered
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`obvious by one of ordinary skill in the art as of July 14, 2007.
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`18.
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`I understand that a claim in a patent is obvious when the differences
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`between the subject matter sought to be patented and the prior art are such that the
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`subject matter as a whole would have been obvious to a person of ordinary skill in
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`the art in the field of the invention ("POSA") at the time of the invention.
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`19.
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`I understand that an obviousness analysis requires the following
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`factual inquiries: (1) determining the scope and content of the prior art; (2)
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`ascertaining the differences between the claimed invention and the prior art; and
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`(3) resolving the level of ordinary skill in the pertinent art.
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`20.
`
`I understand that there are several rationales that may support a
`
`conclusion of obviousness. Examples of these include: (1) combining prior art
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`15
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`Declaration of Dr. Jeremy Edwards
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`elements according to known methods to yield predictable results; (2) simple
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`substitution of one known element for another to obtain predictable results; (3) use
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`of known technique to improve similar devices (methods, or products) in the same
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`way; (4) applying a known technique to a known device (method, or product)
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`ready for improvement to yield predictable results; (5) “obvious to try” – choosing
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`from a finite number of identified, predictable solutions, with a reasonable
`
`expectation of success; (6) known work in one field of endeavor may prompt
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`variations of it for use in either the same field or a different one based on design
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`incentives or other market forces if the variations are predictable to one of
`
`ordinary skill in the art; and (7) some teaching, suggestion, or motivation in the
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`prior art that would have led one of ordinary skill to modify the prior art reference
`
`or to combine prior art reference teachings to arrive at the claimed invention.
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`21.
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`I understand that the combination of familiar elements according to
`
`known methods is likely to be obvious when it does no more than yield
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`predictable results. I understand that, if a technique has been used to improve
`
`one method or device, and a skilled person would recognize that it would improve
`
`similar methods or devices in the same way, using that technique to improve the
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`latter methods or devices would have been obvious unless its actual application
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`yields unexpected results or challenges in implementation.
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`22.
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`I understand that the obviousness analysis can take into account the
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`Declaration of Dr. Jeremy Edwards
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`“ordinary innovation” that does no more than yield predictable results, which are
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`inferences and creative steps that a skilled person would employ.
`
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`III. Person of Ordinary Skill in the Art
`23.
`I have been instructed for the purpose of this Declaration to opine on
`
`the knowledge and understanding of a person of ordinary skill in the art as of July
`
`14, 2007.
`
`24.
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`I have been informed and understand that a person or ordinary skill in
`
`the art (“POSA”) is a hypothetical person who is presumed to have known all of
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`the relevant art at the time of the invention, including from the scientific,
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`technical, and/or patent literature. Therefore, a POSA would have been familiar
`
`with each of the prior art references cited herein, and the full range of teachings
`
`they contain. I have also been informed and understand that, in determining the
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`level of skill in the art, one may consider: the type of problems encountered in
`
`the art, prior art solutions to those problems, the rapidity with which innovations
`
`are made, the sophistication of the technology, and the educational level of active
`
`workers in the field. A POSA thinks along the lines of the conventional wisdom
`
`in the art, and is a person of ordinary creativity.
`
`25.
`
`In my opinion, a person or ordinary skill in the art ("POSA") at the
`
`time of the alleged inventions claimed by the ‘263 patent, would have knowledge
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`Declaration of Dr. Jeremy Edwards
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`of molecular biology, a Ph.D. in molecular biology, and experience in nucleic
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`acid amplification techniques, detection, and analysis. A POSA would be aware
`
`of pertinent art, including from the scientific, technical, and/or patent literature;
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`think along lines of conventional wisdom; and possess ordinary creativity.
`
`
`
`IV. The ‘263 Patent
`A. Brief Technical Overview of the ‘263 Patent
`26. The ‘263 patent is directed to a nicking and extension amplification
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`reaction for the exponential amplification of nucleic acids.
`
`27.
`
`In the “Summary” section, the ‘263 patent states:
`
`Provided herein are methods of amplifying nucleic acid target
`sequences that rely on nicking and extension reactions and amplify
`shorter
`sequences
`in a quicker
`timeframe
`than
`traditional
`amplification reactions, such as, for example, strand displacement
`amplification reactions. col. 3, lns. 38-42.
`
`28.
`
`It is my opinion that the claims of the ‘263 patent are anticipated by
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`or rendered obvious by the prior art. Ehses, Ehses-Dissertation, and Piepenburg
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`teach nicking and extension amplification reactions, as presented in the granted
`
`claims. It is my opinion that Ehses, Ehses-Dissertation, Piepenburg, Kong, and
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`Kato teach or describe all of the features of Claims 1-8 and 10-35.
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`Declaration of Dr. Jeremy Edwards
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`Prosecution History of the ‘263 Patent
`
`I have reviewed the prosecution history of the ‘263 patent, attached as
`
`B.
`29.
`
`[Ex. 1009].
`
`30. The primary prior art references at issue in this Petition are Ehses,
`
`Ehses-Dissertation, and Piepenburg. Ehses was cited by Applicant in an
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`Information Disclosure Statement filed August 11, 2016, but never served as the
`
`basis for any rejection. Ehses-Dissertation was never cited. U.S. Patent No.
`
`7,399,590, corresponding to Piepenburg, was cited by Applicant in an
`
`Information Disclosure Statement filed January 9, 2015, but never served as the
`
`basis for any rejection.
`
`31.
`
`It is clear that the Examiner did not apprehend the full disclosures of
`
`the References because none of the References served as the basis for an
`
`anticipation or obviousness rejection. See File history of the ‘263 patent. In
`
`order to secure patentability, the claims of the ‘263 patent were amended to recite:
`
`
`
`
`
`
`
`without ...subjecting the target nucleic acid to a thermal denaturation
`
`step. See January 9, 2015 Response to Office Action, p. 2, and July
`
`27, 2015 Response-to-Office-Action, p. 2;
`
` combining in a single step…with an amplification reagent mixture.
`
`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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`Declaration of Dr. Jeremy Edwards
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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
`
`within 10 minutes. See September 2, 2016 Response to Office
`
`Action, p. 3.
`
`
`
`32. These limitations were allegedly not taught by the prior art.
`
`However, these claim limitations were disclosed in the References, as discussed
`
`herein below. Had the Examiner recognized these teachings in the References,
`
`the ‘263 patent would not have been allowed.
`
`C. Construction of Terms Used in the Claims
`33.
`I set forth below constructions for specific claim terms. These
`
`constructions are, in my opinion, the only constructions required for the purposes
`
`of the present analysis. However, I reserve the right to supplement or amend my
`
`opinions as to the construction of the claims to the extent the meaning of other
`
`claim terms may be disputed. I also reserve the right to supplement or amend
`
`my opinions as to the construction of the claims in light of new evidence or expert
`
`discovery that may come to light. Finally, by setting forth the constructions
`
`below, I am not expressly or implicitly acknowledging that the claims are definite,
`
`and, in fact, it is my opinion that many of the claim terms are indefinite. I reserve
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`the right to address indefiniteness in connection with any litigation involving the
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`Declaration of Dr. Jeremy Edwards
`
`
`‘263 patent.
`
`a.
` “a sample comprising a target nucleic acid”
`34. The ‘263 patent does not offer a specialized definition of the term “a
`
`sample [from an animal, plant or food] comprising a target nucleic acid.” Under
`
`the plain and ordinary meaning of this term to a POSA, it is understood to mean a
`
`representative portion of an animal, plant, or food that contains a polynucleotide.
`
`35. Dependent claim 15 specifies that the target nucleic acid (“Target”)
`
`can be “synthetic double-stranded DNA and synthetic single-stranded DNA.”
`
`Thus, the “target nucleic acid” of Claim 1 must embrace multiple types of nucleic
`
`acids. Because Claim 15 recites the Target can be “synthetic double-stranded
`
`DNA and synthetic single-stranded DNA,” the term “sample” cannot be
`
`construed as limited to samples that only occur in nature, under the doctrine of
`
`claim differentiation.
`
`b.
`
`“a thermal denaturation step associated with amplification
`of the target polynucleotide sequence”
`36. The ‘263 patent does not off