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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`
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`THERMO FISHER SCIENTIFIC INC.
`Petitioner
`
`v.
`
`Bio-Rad Laboratories, Inc.
`Patent Owner
`
`
`
`
`
`
`
`
`Patent No. 8,236,504
`Issued: August 7, 2012
`Filed: June 30, 2010
`Inventors: Kordunsky et al.
`
`Title: SYSTEMS AND METHODS FOR FLUORESCENCE DETECTION
`WITH A MOVABLE DETECTION MODULE
`
`
`
`
`
`
`Inter Partes Review No. IPR2017-00055
`_______________
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`
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`DECLARATION OF RICHARD MATHIES, PH. D.
`
`THERMO FISHER EX. 1002
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`Agilent Exhibit 1251
`Page 1 of 71
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`TABLE OF CONTENTS
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`I.
`
`Overview and Summary of Opinions .............................................................. 1
`
`II. My background and qualifications .................................................................. 2
`
`III. List of documents I considered in formulating my opinions........................... 5
`
`IV. Person of Ordinary Skill in the Art .................................................................. 7
`
`V.
`
`The level of ordinary skill in the pertinent art and the state of the art before
`May 8, 2003 ..................................................................................................... 9
`
`VI. Overview of the '504 Patent...........................................................................12
`
`VII. Claim Construction ........................................................................................14
`
`VIII. Basis of my analysis with respect to obviousness and objective indicia of
`nonobviousness ..............................................................................................15
`
`IX. Summary of Grounds .....................................................................................17
`
`X. Ground 1: Claims 1-3, 6-11, 13-17, 19, 20 and 22 would have been obvious
`in view of Pantoliano, Miller, and Gambini ..................................................18
`
`XI. Ground 2: Claim 21 would have been obvious in view of Pantoliano,
`Miller, Gambini and Li ..................................................................................48
`
`XII. Ground 3: Claims 1-3, 6-7, 9, 13-14, 16, 19, 20 and 22 would have been
`obvious in view of Iwasaki, Pantoliano and Gambini ...................................48
`
`XIII. Ground 4: Claims 9, 11, 14 and 17 would have been obvious over the
`combination of Iwasaki, Pantoliano and Gambini in view of Miller ............65
`
`XIV. Ground 5: Claim 21 would have been obvious over the combination of
`Iwasaki, Pantoliano and Gambini in view of Li ............................................66
`
`XV. Objective indicia of nonobviousness .............................................................67
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`XVI. Conclusion .....................................................................................................68
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`I, Richard Mathies, hereby declare as follows.
`
`I.
`
`Overview and Summary of Opinions
`
`1.
`
`I am over the age of eighteen (18) and otherwise competent to make
`
`this declaration.
`
`2.
`
`I have been retained as an expert witness on behalf of THERMO FISHER
`
`SCIENTIFIC INC. for the above-captioned inter partes review (IPR). I am being
`
`compensated for my time in connection with this IPR at my standard consulting
`
`rate, which is $500 per hour. I understand that the petition for inter partes review
`
`involves U.S. Patent No. 8,236,504 ("the '504 Patent"), Ex. 1001. The '504 Patent,
`
`entitled "Systems and methods for fluorescence detection with a movable detection
`
`module," issued on Aug. 7, 2012, from U.S. App. No. 12/827,521, which was filed
`
`on Jun. 30, 2010. Ex. 1001. The '504 Patent claims priority to App. No. 11/555,642
`
`filed Nov. 1, 2006, which is a continuation of App. No. 10/431,708, filed May 8,
`
`2003. Id., Ex. 1007; Ex. 1031. I further understand that, according to the first page
`
`of the patent, the '504 Patent is assigned to Bio-Rad Laboratories, Inc. ("the
`
`patentee"). I understand that the earliest asserted priority date for the '504 Patent is
`
`May 8, 2003.
`
`3.
`
`In preparing this Declaration, I have reviewed the '504 Patent, its file
`
`history (Ex. 1004), and considered each of the documents cited herein, in light of
`
`general knowledge in the art (i.e., field) before May 8, 2003. In formulating my
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`opinions, I have relied upon my more than 40 years' experience, education, and
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`knowledge in the relevant art. In formulating my opinions, I have also considered
`
`the viewpoint of a person of ordinary skill in the art ("artisan") before May 8,
`
`2003. A summary of my opinions follows.
`
`4.
`
`It is my opinion that the claims of the '504 Patent would have been
`
`obvious in view of prior art as discussed in more detail below.
`
`5.
`
`Further, I have reviewed the '504 Patent file history (Ex. 1004), and I
`
`am not aware of any objective indicia of nonobviousness that would support
`
`patentability of the claims of the '504 Patent.
`
`II. My background and qualifications
`
`6.
`
`I am an expert in the design of analytical instruments for fluorescence
`
`detection in biological applications, including thermal cyclers. I have been an
`
`expert in this field since well before 2003. In particular, I have worked on the
`
`development and optimization of fluorescence scanning detectors since 1990 and
`
`have extensively applied this technology to the detection of capillary array
`
`electrophoresis DNA sequencing and to fluorescence detection of DNA in gels and
`
`in microtiter plates. I am also expert in the development of chip-based PCR
`
`systems coupled to electrophoresis analysis by fluorescence scanners for fragment
`
`sizing and sequencing as illustrated by many publications including 193, 255, 258,
`
`334, 341, 348, and 387 in my attached publication list. Ex. 1003.
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`7.
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`I am presently Professor of the Graduate School, University of
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`California, Berkeley, and have been in this position since 2013. I have served at the
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`University of California, Berkeley since 1976, where before my current position I
`
`was Dean, College of Chemistry (2008-2013), Director of the Center for Analytical
`
`Biotechnology (2003-2008), Professor of Chemistry (since 1986), Associate
`
`Professor of Chemistry, (1982-1986), and Assistant Professor of Chemistry, (1976-
`
`1982). My prior work experience is listed on my CV. Ex. 1003.
`
`8.
`
`I earned a B. S. in Chemistry from the University of Washington
`
`(1968), an M. S. in Physical Chemistry from Cornell University (1970) and a Ph.
`
`D. in Physical Chemistry from Cornell University (1974). Ex. 1003.
`
`9.
`
`Throughout my career, I have published over 450 scientific articles
`
`and books or book chapters on topics such as analytical instrumentation design,
`
`including fluorescence detectors and thermal cyclers. I regularly attend scientific
`
`and technology conferences where I interact with others in the fields of optics,
`
`physics, engineering (e.g., mechanical, electrical or structural), analytical or
`
`physical chemistry, chemistry, biology or a related field in the engineering,
`
`biological or chemical sciences. A list of my publications and presentations is
`
`found in my curriculum vitae. Ex. 1003.
`
`10.
`
`I have received several honors in my career related to my research and
`
`contributions to the field of analytics and instrumentation. For example, I am a
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`Fellow of the National Academy of Inventors (NAI) (2015), G. N. Lewis Professor
`
`of Chemistry (2008-2013), G. F. Smith Memorial Lecturer, Univ. of Illinois at
`
`Urbana (2011), ACS Analytical Division Award in Chemical Instrumentation
`
`(2010), Dole Lectures in Physical Chemistry, Northwestern Univ. (2010), Fellow
`
`of the Society for Applied Spectroscopy (2008), First Dow Harvard-MIT Lecturer
`
`(2007), Eli Lilly/Indiana University Distinguished Lecturer (2006), Invited
`
`Member, Royal Society of Chemistry (2005), Fellow of Optical Society of
`
`America (2004), Kolthoff Lectures, University of Minnesota (2004), Ellis R.
`
`Lippincott Award from Optical Society of America (2004), Association for
`
`Laboratory Automation (2001) Research Award (2001), Frederick Conference on
`
`Capillary Electrophoresis Award (1998), A. D. Little Lectures, Massachusetts
`
`Institute of Technology (1998), Millner Memorial Lecturer, Duke University
`
`(1997), First Carl Rollinson Memorial Lecturer, University of Maryland (1996),
`
`(1995) Reilly Lecturer in Physical Chemistry, University of Notre Dame (1995).
`
`Ex. 1003.
`
`11. Thus, throughout my career, I have had extensive experience in the
`
`design or manufacture of biological analysis instruments, including optical
`
`components for fluorescence detection, for example in thermocyclers and scanners.
`
`In view of my education, experience, and expertise described above, I am an expert
`
`in the field of optical detection devices, including in thermal cyclers.
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`III. List of documents I considered in formulating my opinions
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`12.
`
`In formulating my opinions, I considered all of the references cited in
`
`this Declaration, including the documents listed below.
`
`Exhibit No.
`
`Description
`
`1001 Kordunsky et al., “Systems and methods for fluorescence detection
`with a movable detection module” U.S. Patent No. 8,236,504 (Filed:
`Jun. 30, 2010; Issued: Aug. 7, 2012)
`1002 Declaration of Professor Richard Mathies
`1003
`Curriculum Vitae of Professor Richard Mathies
`1004
`File History for U.S. Patent No. 8,236,504
`1005
`Pantoliano, et al., “Method for identifying lead compound”
`U.S. Patent 6,303,322 (Filed: Jan. 5, 2000; Issued: Oct. 16,
`2001)
`1006 Miller, et al., “Compact scan head with multiple scanning
`modalities” U.S. Patent No. 5,528,050 (Filed: Jul. 24, 1995;
`Issued: Jun. 18, 1996)
`1007 Gambini, et al., “Instrument for monitoring polymerase chain
`reaction of DNA” International Publication No. WO99/60381
`(Filed: May 17, 1999; Published: Nov. 25, 1999)
`Iwasaki, et al., “DNA chip reading head and DNA chip reader”
`Japanese Publication No. JP2001-242081 (Filed: Feb. 29, 2000;
`Published: Sep. 7, 2001)
`Certified Translation of Iwasaki, et al., “DNA chip reading head
`and DNA chip reader” Japanese Publication No. JP2001-242081
`(Filed: Feb. 29, 2000; Published: Sep. 7, 2001) (Certification
`Document Included)
`Fitzgerald, D. “Up to Speed on PCR” The Scientist, Vol. 14,
`Issue 23, Nov. 27, 2000, pp. 31-33
`1011 DeFrancesco, L. “Real-Time PCR Takes Center Stage” Analytical
`Chemistry, Product Review, Apr. 2003, pp. 175A-179A
`Lauermann, L. “Advances in PCR Technology” Animal Health
`Research Reviews, Vol. 5, Issue 2, Dec. 2004, pp. 247-248
`1013 Meisenholder, G. “New Lids on the Block - LabConsumer
`Annual Review of Thermal Cyclers” The Scientist, Vol. 13, Issue
`23, Nov. 22, 1999, pp. 17-19
`Constans, A. “Some Like It Hot: A Thermal Cycler Roundup” The
`
`1014
`
`
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`1008
`
`1009
`
`1010
`
`1012
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`1015
`
`1016
`
`1018
`
`Scientist, Vol. 15, Issue 24, Dec. 10, 2001, pp. 32-35
`Sandell, D. “Slip cover for heated platen assembly” U.S. Publication
`No. 2004/0018610 (Filed: Jul. 23, 2002; Published: Jan. 29, 2004)
`Lee, et al., “Fluorometer with low heat-generating light source”
`International Publication No. WO01/35079 (Filed: Nov. 9, 2000;
`Published: May 17, 2001)
`1017 Higuchi, et al. “Monitoring multiple reactions simultaneously and
`analyzing same” European Patent No. EP0640828 (Filed: Aug. 16,
`1994; Issued: Jun. 10, 2000)
`Bordenkircher, et al., “PCR sample handling device” U.S. Patent No.
`6,514,750 (Filed: Jul. 3, 2001; Issued: Feb. 4, 2003)
`1019 Woudenberg, et al. “System for real time detection of nucleic acid
`amplification products” U.S. Patent No. 5,928,907 (Filed: Dec. 2,
`1996; Issued: Jul. 27, 1999)
`1020 Woudenberg, et al. “System for real time detection of nucleic acid
`amplification products” International Publication No. WO95/30139
`(Filed: Apr. 19, 1995; Published: Nov. 9, 1995)
`Chu, et al., “Temperature control for multi-vessel reaction apparatus”
`International Publication No. WO01/08800 (Filed: Jul. 11, 2000;
`Published: Feb. 8, 2001)
`Brown, et al. “Flexible heading cover assembly for thermal cycling
`of samples of biological material” (Filed: Oct. 2, 2002; Issued: May
`4, 2004)
`Ishiguro, et al. “Thermal cycling reaction apparatus and reactor
`therefore” U.S. Patent (Filed: Jan. 25, 1996; Issued: Apr. 7, 1998)
`1024 Diggle, et al. “Automation of Fluorescence-Based PCR for
`Confirmation of Meningococcal Disease” Journal of Clinical
`Microbiology, Vol. 39, No. 12, 2001, pp. 4518-4519
`Bio-Tek FL600 “Fluorescence Plate Reader” Hardware Guide, Bio-
`Tek Instruments, Inc., Part No. 6001000, Jun. 1998, Revision D
`1026 Harju, et al. “Apparatus for imaging biochemical samples on
`substrates” U.S. Patent 5,780,857 (Filed: Oct. 4, 1996; Issued: Jul.
`14, 1998)
`Pantoliano, et al., “Microplate thermal shift assay for ligand
`development using 5-(4″-dimethylaminophenyl)-2-(4′-phenyl)
`oxazole derivative fluorescent dyes” U.S. Patent 6,569,631 (Filed:
`Nov. 12, 1999; Issued: May 27, 2003)
`1028 Wittwer, et al. “Multiplex genotyping using fluorescent hybridization
`probes” U.S. Patent 6,140,054 (Filed: Sep. 30, 1998; Issued: Oct. 31,
`2000)
`
`1021
`
`1022
`
`1023
`
`1025
`
`1027
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`1031
`
`1032
`
`1029 Hueton, et al. “High-speed fluorescence scanner” U.S. Patent
`5,459,325 (Filed: Jul. 19, 1994; Issued: Oct. 17, 1995)
`1030 Hayashi, et al. “Scanner-type fluorescence detection apparatus using
`small sized excitation light source” U.S. Patent 6,515,743 (Filed:
`Sep. 22, 2000; Issued Feb. 4, 2003)
`Fernandes, et al. “Mutli[sic.]-functional photometer with movable
`linkage for routing optical fibers” U.S. Patent 5,436,718 (Filed: Jul.
`30, 1993; Issued: Jul. 25, 1995)
`Stumbo, et al., “Light detection device with means for tracking
`sample sites” U.S. Patent 6,310,987 (Filed: Jan. 23, 2001; Issued:
`Oct. 30, 2001
`1033 Kimura, et al. “Quantitative Analysis of Epstein-Barr Virus Load by
`Using a Real-Time PCR Assay” Journal of Clinical Microbiology,
`Vol. 37, No. 1, Jan. 1999, pp. 132-136
`1034 Ackley, et al. “Generic handheld symbology scanner with modular
`optical sensor” U.S. Patent 6,003,775 (Filed: Jun. 11, 1997; Issued:
`Dec. 21, 1999)
`1035 Kawakami, H. “Carriage and recording apparatus” U.S. Patent
`6,520,625 (Filed: Aug. 17, 2000; Issued: Feb. 18, 2003)
`1036 Heffelfinger, et al. “Tunable excitation and/or tunable detection
`microplate reader” U.S. Patent 5,784,152 (Filed: Oct. 11, 1996;
`Issued: Jul. 21, 1998)
`1037 Morin, “High-Throughput Single Nucleotide Polymorphism
`Genotyping by Fluorescent 5’ Exonuclease Assay” BioTechniques,
`Vol. 27, Sep. 1999, pp. 538-552
`1038 U.S. Patent Application No. 10/431,708 filed May 8, 2003
`Kordunsky et al., “Systems and methods for fluorescence detection
`with a movable detection module”
`Li, et al. “Fluorescence quantitative PCR analyzing system”
`Chinese Publication No. CN1379236 (Filed: Apr. 12, 2001;
`Published: Nov. 13, 2002)
`Certified Translation of Li, et al. “Fluorescence quantitative PCR
`analyzing system” Chinese Publication No. CN1379236 (Filed: Apr.
`12, 2001; Published: Nov. 13, 2002) (Certification Document
`Included)
`
`1039
`
`1040
`
`IV. Person of Ordinary Skill in the Art
`
`13. A person of ordinary skill in the art ("artisan") is a hypothetical
`
`person who is presumed to be aware of all pertinent art, thinks along conventional
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`wisdom in the art, and is a person of ordinary creativity. An artisan in the technical
`
`field of the '504 Patent – optical detection devices, including in thermal cyclers –
`
`would have had knowledge of the scientific literature concerning the design and
`
`manufacture of analytical instruments for biological applications, which included
`
`optical detection devices and scanning assemblies, including but not limited to
`
`thermal cyclers, sequencers, microarray readers, fluorimeters, plate readers and
`
`scanners, before May 8, 2003.
`
`14. With respect to the subject matter of the '504 Patent, an artisan would
`
`typically have had (i) an undergraduate degree (e.g., B.Sc. or B.A.) in optics,
`
`physics, engineering (e.g., mechanical, electrical or structural), analytical or
`
`physical chemistry, chemistry, biology or a related field in the engineering,
`
`biological or chemical sciences, and have had at least about one year of experience
`
`in the design or manufacture of biological analysis instruments, including optical
`
`components for fluorescence detection, for example in thermocyclers and scanners.
`
`Also, an artisan may have worked as part of a multidisciplinary team and drawn
`
`upon not only his or her own skills, but of others on the team, e.g., to solve a given
`
`problem. For example, a physicist, biologist, chemist and/or an optical engineer
`
`may have been part of a team.
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`V.
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`The level of ordinary skill in the pertinent art and the state of the art
`before May 8, 2003
`
`15.
`
`I understand that the face of the '504 Patent claims priority to U.S.
`
`patent App. No. 11/555,642 filed Nov. 1, 2006, which is a continuation of App.
`
`No. 10/431,708, filed May 8, 2003. Ex. 1001, p. 1, section (60). Therefore, the
`
`following overview and discussion throughout this Declaration presents the state of
`
`the art before May 8, 2003.
`
`16. Before May 8, 2003, the skill level and knowledge of a person of
`
`ordinary skill ("artisan") was exceptionally deep and rich with respect to the
`
`claimed subject matter. The claims are directed to thermal cyclers – devices which
`
`were not merely a matter of academic interest, but part of everyday life to artisans
`
`since the advent of "end point" PCR in the mid-1980s, and of real-time PCR (i.e.,
`
`quantitative PCR that involves optical detection during PCR) in the 1990s. Ex.
`
`1010, 1; Ex. 1013, 17; Ex. 1012, 1. Real-time thermal cyclers (hereafter "cyclers")
`
`were found in every lab and clinic, and typically were one of the most-used
`
`instruments there. Id. The claims recite features that were not only taught in the art,
`
`but were already implemented in cyclers on the market well before 2003, the
`
`effective date of the claims. In fact, artisans did not need the teachings of the
`
`applied references to recognize the various features of the claims, and to find the
`
`claims obvious.
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`17. For example, artisans already knew and used a "heating element"
`
`(claim 1) or "heater" (claim 13) with a "plurality of openings" as claimed, since
`
`such heating elements were already marketed in most cyclers. So-called "heated
`
`lids" were already in use, which were placed on sample tubes to prevent sample
`
`condensation; these heated lids started out as high-end "optional" accessories for
`
`end-point PCR instruments in the early 1990s (before real-time cyclers were on the
`
`market) to avoid condensation of the heated liquid contents onto the caps of sample
`
`tubes throughout PCR. Ex. 1014, 1; Ex. 1013, 17, 19. Since such condensation
`
`further obstructed optical detection through the caps, heated lids became a
`
`"standard" component of real-time cyclers by the late 1990s. Id. The '504 Patent
`
`itself acknowledges that its "lid heater" could be of "conventional design." Ex.
`
`1001, 5:40-41. And because sample tubes in cyclers with metal sample blocks
`
`were typically monitored from above, through the heated lids, the lids had optical
`
`openings to let light through, just as the claims require. I am aware of at least eight
`
`prior-art references disclosing cyclers having the claimed heating element with
`
`openings. Ex. 1015, ¶46; Ex. 1016, 17:31-35; Ex. 1017, ¶112-113; Ex. 1018, 5:55-
`
`62; Ex. 1019, Fig. 1, 5:43-61; Ex. 1020, 7:8-23; Ex. 1021, 7:28-8:9; Ex. 1022,
`
`15:18-36.
`
`18.
`
`In addition, the claimed in-head placement of optical components
`
`within the optics head itself was already found in scanning devices used on DNA
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`samples on chips and microtiter wells – the most common sample-well format in
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`cyclers. Ex. 1006, 3:2-5; Ex. 1010, p5; Ex. 1011, 178A, right col.. The pertinent
`
`and analogous field for fluorescence detection in real-time cyclers was the field of
`
`optical devices in general, not limited to cyclers alone. Ex. 1011, 178A, right col.;
`
`Ex. 1018, 1:53-59; Ex. 1023, 5:51-6:3. There were historical reasons for this:
`
`cyclers were in advanced development as non-optical devices well before real-time
`
`PCR introduced optical detection into the world of cyclers in 1993. Id. Rather than
`
`reinventing optical systems from scratch, artisans making optical cyclers naturally
`
`looked to existing optical systems in other devices as relevant. Id. Real-time PCR
`
`merely required scanning or imaging of a 2D planar area, something practically
`
`any optical detector could do. Artisans performed real-time PCR by combining
`
`non-optical thermal cyclers with a wide variety of optical devices, such as video
`
`cameras, fluorometers, plate readers and laser scanners. Id., Ex. 1017, ¶61; Ex.
`
`1024, 4518; Ex. 1025, p. 3-10, Fig. 3-6. Only the desired scanning format, rather
`
`than the nature of the sample, dictated the choice of scanner: artisans used the same
`
`scanner to scan gels, phosphorimage plates, glass slides and microtiter-well plates
`
`alike. Ex. 1006, 3:2-5. In illustrative examples, a prior-art DNA chip reader had an
`
`optics head design taken from optical-disk devices; and a prior-art gel scanner had
`
`an optical system taken from a microscope. Ex. 1008, ¶26; Ex. 1026, 2:22-25.
`
`Moreover, cyclers themselves were also designed to accept an equally wide variety
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`of sample formats such as tubes, microwells, capillaries, and glass slides. Ex. 1014,
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`7. Artisans thus treated the general body of optical-detection systems as pertinent
`
`and analogous art for real-time cyclers, irrespective of sample format. Id.
`
`Microtiter plate readers such as Miller's scan head were a natural match for cyclers
`
`since the same microtiter format was the most popular well format in cyclers, and
`
`devices which integrated thermal cyclers with plate readers were on the market by
`
`2001. Ex. 1024, 4518; Ex. 1010, p5; Ex. 1011, 178A, right col. Since optics heads
`
`had already been designed to scan microtiter wells in other devices, it was only a
`
`matter of time – not inventiveness – before these optics heads were used in cyclers
`
`as well. In fact, they already had been. Ex. 1040, 8:16-9:7; Ex. 1028, 11:24-34,
`
`Fig. 10; Fig. 3.
`
`VI. Overview of the '504 Patent
`
`19.
`
`I understand that this Declaration is being submitted together with a
`
`petition for inter partes review of claims 1-3, 6-11, 13-17 and 19-22 of the '504
`
`Patent. I have reviewed the '504 Patent, its file history, and App. No. 10/431,708,
`
`filed May 8, 2003, to which the '504 Patent claims priority. Ex. 1001, Ex. 1004,
`
`Ex. 1038. In assessing the '504 Patent, I have considered the teachings of the
`
`scientific literature before May 8, 2003, in light of general knowledge in the art
`
`before that date.
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`20. The '504 Patent claims are directed to a thermal cycler with a movable
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`detection module which contains an internal light generator and a detector
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`(hereafter, "optics head"), attached to a shuttle movably mounted on a support,
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`where the optics head views sample wells through openings in a heating element.
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`21. The '504 Patent has 22 claims. Claims 1 and 13 are the only
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`independent claims. Each claim of the '504 Patent requires the presence of a self-
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`contained movable "detection module" ("optics head") which contains both a light
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`generator and a detector within its housing. Claim 1 is exemplary and is provided
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`below:
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`1. A fluorescence detection apparatus for analyzing samples
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`located in a plurality of wells in a thermal cycler, the apparatus
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`comprising:
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`a support structure attachable to the thermal cycler;
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`a shuttle movably mounted on the support structure; and
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`a detection module attached to the shuttle, the detection
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`module including:
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`a housing having an opening oriented toward the plurality
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`of wells;
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`an excitation light generator disposed within the housing;
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`and
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`an emission light detector disposed within the housing,
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`wherein, when the support structure is attached to the
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`thermal cycler, a heating element is disposed between the
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`detection module and the sample wells and the shuttle is
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`movable
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`to position
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`the detection module
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`in optical
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`communication with different wells of the plurality of wells
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`through a plurality of openings extending through the heating
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`element.
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`22.
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`Independent claim 13 is similar to claim 1, but indicates that the
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`cycler has an "exterior housing." Ex. 1001, claim 13.
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`Ex. 1001, claim 1.
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`23.
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`I understand that claims 2 to 12 are "dependent" from claim 1 because
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`they refer directly to claim 1, and similarly that claims 14-22 are "dependent" from
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`claim 13. Ex. 1001. I also understand that claims 4 and 5 are dependent from claim
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`3 because each of these claims refers directly to claim 3.
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`VII. Claim Construction
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`24.
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`I understand that terms of the claims are to be given their broadest
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`reasonable interpretations in light of the '504 Patent's specification. I also
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`understand that the prosecution history of the patent should be consulted in
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`determining claim meaning. I further understand that these terms should be given a
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`meaning consistent with how they would be viewed by an artisan before May 8,
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`2003, and my analyses below are presented from such a viewpoint. Any term I
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`have not expressly interpreted below, I have given its broadest reasonable
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`interpretation consistent with the patent’s specification and the prosecution history.
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`The interpretations herein are consistent with the claim constructions offered in
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`Petitioner's concurrent petition IPR2017-00054 against the same claims on other
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`grounds.
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`VIII. Basis of my analysis with respect to obviousness and objective indicia of
`nonobviousness
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`25.
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`I understand that an obviousness analysis involves properly construing
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`a patent claim and then comparing that claim to the prior art to determine whether
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`the claimed invention would have been obvious to a skilled person in view of the
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`prior art, and in light of the general knowledge in the art.
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`26.
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`I also understand that obviousness can be established by combining or
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`modifying the teachings of the prior art to achieve the claimed invention. I
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`understand that the reason to combine prior art references must be shown. This
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`reason to combine can come from a variety of sources, not just the prior art itself or
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`the specific problem the patentee was trying to solve. And I understand that the
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`references themselves need not provide a specific hint or suggestion of the
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`alteration needed to arrive at the claimed invention; the analysis may include
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`recourse to logic, judgment, and common sense available to a skilled person that
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`does not necessarily require explanation in any reference. It is also my
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`understanding that where there is a reason to modify or combine the prior art to
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`achieve the claimed invention, there must also be a reasonable expectation of
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`success in so doing.
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`27.
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`I also understand that a combination of familiar elements according to
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`known methods is likely to be obvious when it does no more than yield predictable
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`results. I also understand that when there is a design need or market pressure to
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`solve a problem and there are a finite number of identified, predictable solutions, a
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`skilled person has good reason to pursue the known options within his or her
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`technical grasp. If this leads to the anticipated outcome, then that outcome is likely
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`a product not of innovation, but of ordinary skill and common sense, and therefore
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`is considered obvious according to patent laws.
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`28.
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`I understand that when a skilled person would have reached the
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`claimed invention through routine optimization, the invention may be deemed
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`obvious. I also understand that such routine optimization involves testing an
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`element or parameter that is termed a "results-effective" variable (that is, a variable
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`that achieves a recognized result). And I understand that routine optimization
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`involves using only routine techniques and ordinary skill of one in the relevant art.
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`I understand that when considering the obviousness of an invention, one should
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`also consider whether there are any objective indicia (also known as secondary
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`considerations) that support the nonobviousness of the invention. I understand that
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`objective indicia of nonobviousness include commercial success, long-felt but
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`unmet need, failure of others, praise in the industry and unexpected superior
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`results.
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`IX. Summary of Grounds
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`29. The table below summarizes the grounds for unpatentability set forth
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`in this Declaration. Throughout my discussion of the Grounds below, I refer to the
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`State of the Art discussed in Section V. The discussion in Section V is relevant
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`throughout the entirety of this Declaration.
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`Ground
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`35 U.S.C. §
`(pre-3/16/2013)
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`Claims
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`Index of References
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`§103(a)
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`§103(a)
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`§103(a)
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`1-3, 6-11, 13-17,
`19, 20, 22
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`21
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`1-3, 6-8, 10, 13,
`15-16, 19, 20, 22
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`§103(a)
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`9, 11, 14 and 17
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`§103(a)
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`21
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`Pantoliano, Miller and
`Gambini
`Pantoliano, Miller,
`Gambini and Li
`Iwasaki, Pantoliano and
`Gambini
`Iwasaki, Pantoliano,
`Gambini and Miller
`Iwasaki, Pantoliano,
`Gambini and Li
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`1
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`2
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`3
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`4
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`5
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`
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`30. U.S. Pat. 6,303,322 ("Pantoliano") published on Oct. 16, 2001.
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`Pantoliano expressly discloses a thermal cycler for PCR, and thus is better art than
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`another patent also to Pantoliano which was applied during prosecution but does
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`not disclose a thermal cycler (U.S. Pat. 6,569,631). Ex. 1005, 42:57-62, Ex. 1027.
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`U.S. Pat. 5,528,050 ("Miller") published on Jun. 18, 1996. WO 99/60381
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`("Gambini ") published on Nov. 25, 1999. Japanese Patent Pub. No. P2001-
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`242081A ("Iwasaki") published on Sep. 7, 2001. Chinese Patent Publ. No. CN
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`1379236A ("Li," Ex. 1039, certified English translation provided as Ex. 1040)
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`published in Chinese on Nov. 13, 2002. Ex. 1039; Ex. 1040. I understand that these
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`publications qualify as prior art to the '504 Patent.
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`31. Each claim is challenged under two non-redundant Grounds, one
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`based on Pantoliano as primary reference, and the other on Iwasaki. Pantoliano
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`discloses a scanning cycler with a generator and detector placed outside the head; it
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`would have obvious to switch to in-head placement as a well-known alternative. In
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`contrast, Iwasaki discloses a self-contained optics head with the generator/detector
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`placed in-head; it would have been obvious to use such an optics head in thermal
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`cyclers for scanning purposes.
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`X. Ground 1: Claims 1-3, 6-11, 13-17, 19, 20 and 22 would have been obvious
`in view of Pantoliano, Miller, and Gambini
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`32. As shown below, claims 1-3, 6-11, 13-17, 19, 20 and 22 would have
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`been obvious over the combination of Pantoliano, Miller, and Gambini. The
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`references together disclosed all elements of the claims, and there were many
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`reasons to combine their teachings, making the claims obvious by their asserted
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`priority date of 2003. A detailed analysis is provided below for representative
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`claim 1 and is also applicable to the other claims as well.
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`33. Determining the scope and content of the prior art and
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`ascertaining the differences from the claims: The scope and conten