Case 1:20-cv-01734-RGA-JLH Document 117 Filed 04/17/23 Page 1 of 7 PageID #: 11067
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`RAVGEN, INC.,
`
`v.
`
`Plaintiff,
`
`ILLUMINA, INC. and VERINATA HEALTH,
`INC.,
`
`Defendants.
`
`RAVGEN, INC.,
`
`v.
`
`Plaintiff,
`
`ARIOSA DIAGNOSTICS, INC.,
`ROCHE SEQUENCING SOLUTIONS, INC.,
`ROCHE MOLECULAR SYSTEMS, INC., and
`FOUNDATION MEDICINE, INC.,
`
`Defendants.
`
`Plaintiff,
`
`RAVGEN, INC.,
`
`v.
`
`MYRIAD GENETICS, INC., and
`MYRIAD WOMEN’S HEALTH, INC.,
`
`Defendants.
`
`C.A. No. 20-cv-1644-RGA-JLH
`
`JURY TRIAL DEMANDED
`
`FILED UNDER SEAL
`
`C.A. No. 20-cv-1646-RGA-JLH
`
`JURY TRIAL DEMANDED
`
`FILED UNDER SEAL
`
`C.A. No. 20-cv-1730-RGA-JLH
`
`JURY TRIAL DEMANDED
`
`FILED UNDER SEAL
`
`RAVGEN, INC.,
`
`v.
`
`BIORA THERAPEUTICS, INC.,
`
`Defendant.
`
`Plaintiff,
`
`C.A. No. 20-cv-1734-RGA-JLH
`
`JURY TRIAL DEMANDED
`
`FILED UNDER SEAL
`Volume 4 of 4
`Contains D27-D60
`
`JOINT APPENDIX TO JOINT CLAIM CONSTRUCTION BRIEF
`
`

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`Case 1:20-cv-01734-RGA-JLH Document 117 Filed 04/17/23 Page 2 of 7 PageID #: 11068
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`Plaintiff’s Exhibits
`Exhibit Documents
`P1
`U.S. Patent No. 7,332,277
`P2
`U.S. Patent No. 7,727,720
`P3
`Declaration Of Dr. Brian G. Van Ness, Ph.D In Support Of Plaintiff Ravgen, Inc.’s
`Opening Claim Construction Brief, dated December 10, 2021
`Dr. Brian G. Van Ness’s Curriculum Vitae
`Supplemental Claim Construction Order (DI 0176), filed November 8, 2021, in the
`action Ravgen, Inc. v. Natera, Inc., No. 1:20-cv-00692-ADA (W.D. Tex.)
`Non-Final Office Action, dated March 17, 2006, from the File History of U.S.
`Patent No. 7,332,277
`Amendment in Response to Non-Final Office Action, dated July 14, 2006, from the
`File History of U.S. Patent No. 7,332,277
`Final Office Action, dated October 12, 2006, from the File History of U.S. Patent
`No. 7,332,277
`Non-Final Office Action, dated January 30, 2007, from the File History of U.S.
`Patent No. 7,332,277
`Non-Final Office Action, dated December 4, 2008, from the File History of U.S.
`Patent No. 7,727,720
`Claim Construction Order (DI 0088), filed June 2, 2021, in the action Ravgen, Inc.
`v. Natera, Inc., No. 1:20-cv-00692-ADA (W.D. Tex.)
`Amended Claim Construction Order (DI 0191), filed December 1, 2021, in the
`action Ravgen, Inc. v. Natera., Inc., No. 1:20-cv-00692-ADA (W.D. Tex.)
`Claim Construction Order (DI 0078), filed June 2, 2021, in the action Ravgen, Inc.
`v. PerkinElmer, Inc., No. 1:20-cv-00822-ADA (W.D. Tex.)
`Claim Construction Order (DI 0065), filed October 5, 2021, in the action Ravgen,
`Inc. v. Quest Diagnostics Inc., No. 6:20-cv-00972-ADA (W.D. Tex.)
`Plaintiff Ravgen, Inc.’s Opening Claim Construction Brief (DI 0050), filed
`December 4, 2020, in the action Ravgen, Inc. v. PerkinElmer, Inc., No. 1:20-cv-
`00822-ADA (W.D. Tex.)
`U.S. Patent No. 5,618,664
`Defendants Natera, Inc.’s and NSTX, Inc.’s Responsive Claim Construction Brief
`(DI 0049), filed January 11, 2021, in the action Ravgen, Inc. v. Natera, Inc., No.
`1:20-cv-00692-ADA (W.D. Tex.)
`Defendants’ Responsive Claim Construction Brief (DI 0055), filed January 8, 2021,
`in the action Ravgen, Inc. v. PerkinElmer, Inc., No. 1:20-cv-00822-ADA (W.D.
`Tex.)
`Claim Construction Order, filed October 5, 2021, in the action Ravgen, Inc. v.
`Laboratory Corporation of America Holdings, No. 6:20-cv-00969-ADA (W.D.
`Tex.)
`P20 Myriad’s Initial Invalidity Contentions, served September 17, 2021, in the action
`Ravgen, Inc. v. Myriad Genetics, Inc., No. 20-cv-1730-RGA-JLH (D. Del.)
`Excerpts from Defendants’ Initial Invalidity Contentions, served September 17,
`2021, in the action Ravgen, Inc. v. Ariosa Diagnostics, Inc., No. 20-cv-1646-RGA-
`JLH (D. Del.)
`
`P21
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`Case 1:20-cv-01734-RGA-JLH Document 117 Filed 04/17/23 Page 3 of 7 PageID #: 11069
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`P22
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`P23
`P24
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`P25
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`P26
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`P27
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`P28
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`P32
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`Chiu et al., “Effects of Blood-Processing Protocols on Fetal and Total DNA
`Quantification in Maternal Plasma”
`Hahn et al., “Quantification of Circulating DNA: In the Preparation Lies the Rub”
`Quest Diagnostics Incorporated’s Claim Construction Sur-Reply (DI 0055), filed
`September 8, 2021, in the action Ravgen, Inc. v. Quest Diagnostics Incorporated,
`No. 6:20-cv-00972-ADA (W.D. Tex.)
`Plaintiff Ravgen, Inc.’s Unopposed Motion to Correct Obvious Error in Claim 81
`of U.S. Patent No. 7,332,277 (DI 0056), filed January 22, 2021, in the action
`Ravgen, Inc. v. Natera, Inc., No. 1:20-cv-00692-ADA (W.D. Tex.)
`Text Order GRANTING Motion to Amend/Correct entered by Judge Alan D.
`Albright, filed April 6, 2021, in the action Ravgen, Inc. v. Natera, Inc., No. 6:20-
`cv-00451-ADA (W.D. Tex.), granting Plaintiff Ravgen, Inc.’s Unopposed Motion
`to Correct Obvious Error in Claim 81 of U.S. Patent No. 7,332,277
`Amicucci et al., “Prenatal Diagnosis of Myotonic Dystrophy Using Fetal DNA
`Obtained from Maternal Plasma”
`Holodniy et al., “Determination of Human Immunodeficiency Virus RNA in
`Plasma and Cellular Viral DNA Genotypic Zidovudine Resistance and Viral Load
`during Zidovudine-Didanosine Combination Therapy”
`U.S. Patent No. 7,291,724
`P29
`U.S. Patent No. 5,576,176
`P30
`P31 Webpage describing Citra Labs ACD-A Product Label (Product Number 9350),
`available at
`https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5bcd261e-ebba-
`4ecb-af22- e5aaeb04499b&type=display as of December 9, 2021
`Lui and Lo, “Circulating DNA in Plasma and Serum: Biology, Preanalytical Issues
`and Diagnostic Applications”
`P33 Webpage describing “Fixation and Fixatives (2) - Factors influencing chemical
`fixation, formaldehyde and glutaraldehyde,” authored by Geoffrey Rolls, and
`available at https://www.leicabiosystems.com/knowledge-pathway/fixation-and-
`fixatives-2-factorsinfluencing-chemical-fixation-formaldehyde-and-glutaraldehyde/
`as of December 9, 2021
`Thavarajah et al., “Chemical and physical basics of routine formaldehyde fixation”
`P34
`P35 Webpage describing “Process of Fixation and the Nature of Fixatives,” authored by
`Geoffrey Rolls, and available at https://www.leicabiosystems.com/knowledge-
`pathway/fixation-and-fixatives-1-the-process-offixation-and-the-nature-of-
`fixatives/ as of December 9, 2021
`P36 Wang et al., “Vitamin E inhibits hemolysis induced by hemin as a membrane
`stabilizer”
`Grau et al., “Dissimilar protection of tocopherol isomers against membrane
`hydrolysis by phospholipase A2”
`Török et al., “Heat Shock protein coinducers with no effect on protein denaturation
`specifically modulate the membrane lipid phase”
`P39 Merriam-Webster.com definition of “wild type,” available at
`https://www.merriamwebster.com/dictionary/wild%20type as of December 8, 2021
`Non-Final Office Action, dated June 15, 2007, from the File History of U.S. Patent
`No. 7,727,720
`
`P37
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`P38
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`P40
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`2
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`P45
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`P46
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`P47
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`P48
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`P49
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`P50
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`P51
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`P52
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`P53
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`P54
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`P56
`P57
`P58
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`Amendment in Response to Non-Final Office Action, dated December 17, 2007,
`from the File History of U.S. Patent No. 7,727,720
`Excerpts from the Concise Dictionary of Biomedicine and Molecular Biology,
`Second Edition, 2002, authored by Pei-Show Juo
`Amendment in Response to Non-Final Office Action, dated May 30, 2007, from
`the File History of U.S. Patent No. 7,332,277
`Declaration of Dr. Brian G. Van Ness, Ph.D In Support Of Plaintiff Ravgen, Inc.’s
`Reply Claim Construction Brief, dated February 11, 2022
`Highlighted excerpts of the deposition transcript of Dr. Michael Metzker, dated
`February 7, 2022
`Highlighted excerpts of Illumina, Inc. v. Ravgen, Inc., IPR2021-01271, Paper 001
`(PTAB July 20, 2021)
`Highlighted excerpts of Illumina, Inc. v. Ravgen, Inc., IPR2021-01272, Paper 001
`(PTAB July 20, 2021)
`Highlighted excerpts of the Request for Ex Parte Reexamination of U.S. Patent No.
`7,727,720, filed on September 24, 2021
`Defendant Quest Diagnostics Incorporated’s Supplemental Claim Construction
`Submission (D.I. 61), filed September 22, 2021, in the action Ravgen, Inc. v. Quest
`Diagnostics Incorporated, No. 6:20-cv-00972-ADA (W.D. Tex.)
`Highlighted excerpts of the deposition transcript of Dr. Wayne W. Grody, M.D.,
`Ph.D, dated January 29, 2021, in the matters Ravgen, Inc. v. Natera, Inc. and
`NSTX, Inc., No. 1:20-cv-00692-ADA (W.D. Tex.) and Ravgen, Inc. v.
`PerkinElmer, Inc., PerkinElmer Genetics, Inc., and Bioo Scientific Corp., No. 1:20-
`cv-00822-ADA (W.D. Tex.)
`Highlighted copy Ravgen’s Initial Infringement Contentions in the action Ravgen,
`Inc. v. Ariosa Diagnostics, Inc., Roche Sequencing Solutions, Inc., Roche
`Molecular Systems, Inc., and Foundation Medicine, Inc., No. 1:20-cv-01646-RGH-
`JLH (D. Del.), served on July 30, 2021
`Highlighted excerpts of the specification of Patent Application No. 10/661,165,
`filed on September 11, 2003, and issued as U.S. Patent No. 7,332,277 on February
`19, 2008
`Highlighted copy of the Amendment After Final Action Under 37 C.F.R. 1.116,
`dated December 12, 2006, from the File History of U.S. Patent No. 7,332,277
`Highlighted copy the Amendment In Response to Non-Final Office Action, dated
`June 2, 2009, from the File History of U.S. Patent No. 7,727,720
`Saito et al., Prenatal DNA diagnosis of a single-gene disorder from maternal
`plasma, 356 LANCET 1170 (2000)
`U.S. Patent No. 10,392,614
`U.S. Patent No. 9,404,150
`U.S. Patent Application Publication No. US 2020/03625415
`
`3
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`Case 1:20-cv-01734-RGA-JLH Document 117 Filed 04/17/23 Page 5 of 7 PageID #: 11071
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`D2
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`D3
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`D4
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`D8
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`Defendants’ Exhibits
`Exhibit Documents
`D1
`Deposition Transcript of Brian G. Van Ness, Ph.D., dated September 1, 2021, in the
`matter of Ravgen, Inc. v. Quest Diagnostics Inc., No. 6:20-cv-00972-ADA (W.D.
`Tex.)
`Reply Declaration of Wayne Grody, Ph.D., Ravgen, Inc. v. PerkinElmer Inc., No. 1-
`:20-cv-00822 (W.D. Tex.) (D.I. 58-1)
`Deposition Transcript of Wayne Grody, Ph.D., Ravgen, Inc. v. PerkinElmer Inc., No.
`1-20-cv-00822 (WDTX) (D.I. 63-1, Ex. 21)
`Plaintiff’s Reply Claim Construction Brief, Ravgen, Inc. v. Natera, Inc., No. 6:20-
`cv-00692 (W.D. Tex.) (D.I. 56)
`D5 Webster’s Third New International Dictionary (2002)
`D6
`Oxford Dictionary of Biochemistry and Molecular Biology, Revised ed. 2000
`D7
`Deposition Transcript of Brian G. Van Ness, Ph.D., dated August 31, 2021, in the
`matter of Ravgen, Inc. v. Laboratory Corporation of America Holdings, No. 6:20-
`cv-00969-ADA (W.D. Tex.)
`Plaintiff’s Opening Claim Construction Brief, Ravgen, Inc. v. PerkinElmer Inc., No.
`1:20-cv-00822 (W.D. Tex. Dec. 4, 2020) (D.I. 50)
`Microsoft Encarta College Dictionary, 2001
`D9
`D10 Merriam-Webster’s Collegiate Dictionary, 10th edition, 1995
`D11
`Emami, et al., titled “Tissue Sources for Accurate Measurement of Germline DNA
`Genotypes in Prostate Cancer Patients Treated with Radical Prostatectomy.”
`Giles, et al., titled “The Science and Art of Clinical Genetic Variant Classification
`and Its Impact on Test Accuracy.”
`Publication by the ACMG Laboratory Practice Committee Working Group, titled
`“ACMG recommendations for standards for interpretation of sequence variations.”
`Dr. Michael L. Metzker’s curriculum vitae
`Lo, et al., titled “Increased Fetal DNA Concentrations in the Plasma of Pregnant
`Women Carrying Fetuses with Trisomy 21.”
`Chapter 12, by Cooper, from The Cell: A Molecular Approach, titled “The Cell
`Surface.”
`Im, et al., titled “Novel Bile Acid Derivatives Induce Apoptosis Via a p53-
`independent Pathway in Human Breast Carcinoma Cells.”
`Sagawa, et al., titled “Protection Against Hydrophobic Bile Salt-Induced Cell
`Membrane Damage by Liposomes and Hydrophilic Bile Salts.”
`Hofmann and Small, titled “Detergent Properties of Bile Salts: Correlation with
`Physiological Function.”
`Clarke, et al., titled “Surface Ultrastructure of Human Leucocytes, Mouse
`Macrophages and Rat Liver Cells, and of Isolated Nuclei and Nucleoli.”
`Hasbold and Hodgkin, titled “Flow Cytometric Cell Division Tracking Using
`Nuclei.”
`O’Brien, titled “A Rapid Method for the Isolation and Collection of Nuclei From
`Whole Cell Suspensions.”
`Chi and Wu, titled “Mechanism of Hemolysis of Red Blood Cell Mediated by
`Ethanol.”
`
`D12
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`D13
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`D14
`D15
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`D16
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`D17
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`D18
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`D19
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`D21
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`D22
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`D23
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`Case 1:20-cv-01734-RGA-JLH Document 117 Filed 04/17/23 Page 6 of 7 PageID #: 11072
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`D27
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`D28
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`D29
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`D30
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`D31
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`D32
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`D33
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`D34
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`D35
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`D36
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`D37
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`D38
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`D39
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`D42
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`D43
`D44
`
`Exhibit Documents
`D24
`Chapter 8, by Melan, from Methods in Molecular Biology, titled “Overview of Cell
`Fixation and Permeabilization.”
`Patent Owner’s Preliminary Response, dated January 28, 2022, in the matter of
`Streck, Inc. v. Ravgen, Inc., IPR2021-01577
`Deposition of Dr. Brian Van Ness, dated October 3, 2022 in the matter of Streck, Inc.
`v. Ravgen, Inc., IPR2021-01577
`Excerpt from the file history for U.S. Patent Application No. 16/918756, filed July
`1, 2020
`Hearing Transcript, dated September 21, 2022, in the matter of Laboratory Corp. of
`America Holdings v. Ravgen, Inc., IPR2021-01026
`Patent Owner’s Sur-Reply to Petitioner’s Reply, dated September 27, 2022, in the
`matter of Illumina, Inc. v. Ravgen, Inc., IPR2021-01272
`Patent Owner’s Response, dated January 27, 2022, in the matter of Laboratory Corp.
`of America Holdings v. Ravgen, Inc., IPR2021-01054
`Deposition of Ravinder Dhallan, M.D., Ph.D., dated July 20, 2021 in the matter of
`Ravgen, Inc. v. Natera, Inc. and NSTX, Inc., Case No. 1:20-cv-692, W.D. Texas
`[CONFIDENTIAL]
`Deposition of Ravinder Dhallan, M.D., Ph.D., dated July 22, 2021 in the matter of
`Ravgen, Inc. v. Natera, Inc. and NSTX, Inc., Case No. 1:20-cv-692, W.D. Texas
`[CONFIDENTIAL]
`ISOGG Wiki,
`from
`Single-nucleotide
`polymorphism,
`https://isogg.org/wiki/Single-nucleotide_polymorphism
`Pei-Show Juo, Concise Dictionary of Biomedicine and Molecular Biology, Second
`Edition, CRC Press (“Juo Dictionary”), dated 2002
`Herbert et al., The Dictionary of Immunology, Fourth Edition, Academic Press
`(“Academic Press Dictionary”), dated 1995
`Cruse & Lewis, Illustrated Dictionary of Immunology, CRC Press (“CRC Press
`Dictionary”), dated 1995
`Abercrombie et al., The New Penguin Dictionary of Biology, Eighth Edition, Penguin
`Books (“Penguin Dictionary 1”), dated 1990
`Thain & Hickman, The Penguin Dictionary of Biology, Tenth Edition, Penguin
`Books (“Penguin Dictionary 2”), dated 2000
`Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, Third
`Edition, John Wiley & Sons (“Wiley Dictionary”), dated 2001
`D40 Walker, Cambridge Dictionary of Biology, Cambridge University Press
`(“Cambridge Dictionary”), dated 1989
`D41 Walker, Chambers Biology Dictionary, Chambers Cambridge (“Chambers
`Dictionary”), dated 1989
`Alberts et al., Molecular Biology of the Cell, Fourth Edition, Garland Science
`(“Alberts”), dated 2002
`Lewin, Genes VII, Oxford University Press (“Genes VII”), dated 2000
`Sambrook & Russell, Molecular Cloning, A Laboratory Manual, Third Edition, Cold
`Spring Harbor Laboratory Press (“Maniatis”), dated 2001
`D45 Wong, Chemistry of Protein Conjugation and Cross-Linking, CRC Press (“Wong
`Textbook), dated 1991
`
`available
`
`at,
`
`5
`
`

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`D47
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`D48
`D49
`D50
`D51
`D52
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`D53
`
`Exhibit Documents
`D46
`Haugland, Handbook of Fluorescent Probes and Research Products, Ninth Edition,
`Molecular Probes (“Molecular Probes Handbook”), dated 2002
`Double-agents™, Cross-linking Reagents, Selection Guide, Pierce Catalog (“Pierce
`Catalog 1”), dated 2001
`Cross-linking Reagents, Pierce Catalog (“Pierce Catalog 2”), dated 1989
`Biochemicals & Reagents, Amphotech Catalog, (“Amphotech Catalog”), dated 2002
`Product Category, Calbiochem Catalog, (“Calbiochem Catalog”), dated 2002
`UVP, Sitemap (“UVP Catalog”), dated 2002
`Chen et al., Progressive disruption of the plasma membrane during renal proximal
`tubule cellular injury, TOXICOLOGY AND APPLIED PHARMACOLOGY 171:1-11 (“Chen
`2001”), dated 2001
`Hasty & Hay, Freeze-fracture studies of the developing cell surface, II. Particle-free
`membrane blisters on glutaraldehyde-fixed corneal fibroblasts are artefacts,
`JOURNAL OF CELL BIOLOGY 78:756–768 (“Hasty 1978”), dated 1978
`Fox et al., Formaldehyde fixation, THE JOURNAL OF HISTOCHEMISTRY AND
`CYTOCHEMISTRY 33:845-853, (“Fox 1985”), dated 1985
`Griffiths et al., On the preparation of cryosections for immunocytochemistry,
`JOURNAL OF ULTRASTRUCTURE RESEARCH 89:65-78 (“Griffiths”), dated 1984
`Yip & Auersperg, The dye-exclusion test for cell viability: Persistence of differential
`staining following fixation, IN VITRO 7:323-329 (“Yip & Auersperg 1972”), dated
`1972
`Penttila et al., Influence of glutaraldehyde and/or osmium tetraoxide on cell volume,
`ion content, mechanical stability, and membrane permeability of Ehrlich ascites
`tumor cells, THE JOURNAL OF CELL BIOLOGY 63:197-214 (“Penttila 1974”), dated
`1974
`Gazi et al., Fixation protocols for subcellular imaging by synchrotron-based Fourier
`transform infrared microspectroscopy, BIOPOLYMERS 77:18-30 (“Gazi 2005”), dated
`2005
`Declaration of Dr. Michael L. Metzker, dated January 21, 2022 (“Metzker”)
`Declaration of Dr. Michael L. Metzker, dated April 3, 2023 (“Metzker II”)
`
`D54
`
`D55
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`D56
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`D57
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`D58
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`D59
`D60
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`6
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