Patent Owner CDx Diagnostic Inc.’s Demonstratives for Oral Argument
`
`U.S. Endoscopy Group, Inc. (Petitioner)
`v.
`CDx Diagnostics Inc. (Patent Owner)
`
`IPR2014-00639 - U.S. Pat No. 6,676,609
`IPR2014-00641 - U.S. Pat No. 7,004,913
`IPR2014-00642 - U.S. Pat No. 6,258,044
`
`Counsel for Patent Owner CDx Peter L. Berger (Reg. No. 24,570)
`Tuvia Rotberg (Reg. No. 58,167)
`Levisohn Berger LLP
`
`David K. Barr (Reg. No. 31,940)
`James S. Blank (Admitted Pro Hac Vice)
`David Soofian (Reg. No. 65,874)
`Kaye Scholer LLP
`
`

`
`Patent Owner CDx Diagnostic Inc.’s Demonstratives for Oral Argument
`
`Background
`
`2
`
`

`
`Layers of glandular epithelial tissue
`
`’609 & ’913 Patents
`
`columnar cells
`
`basement membrane
`
`submucosa
`
`IPR2014-00639 Ex. 1001 at Fig. 5, 9:43-10:7
`IPR2014-00641 Ex. 1001 at Fig. 5, 9:47-10:4
`
`3
`
`

`
`Layers of oral epithelial tissue
`
`Lonky ’044 Patent
`
`Superficial
`Intermediate
`Basal
`Basement Membrane
`
`Submucosa
`
`IPR2014-00642 Ex. 1001 at 4:34-37, 11:56-65
`
`Claims
`2. Apparatus to obtain cells in epithelial tissue
`of the body according to claim 1, wherein said
`bristles collect cells from three layers of said
`epithelial tissue, said three layers comprising
`superficial, intermediate and basal layers, said
`basal layer separated from the submucosa by a
`basement membrane.
`
`3. Apparatus to obtain cells in epithelial tissue
`of the body according to claim 2, wherein said
`bristles of said brush have sufficient stiffness to
`penetrate said basement membrane and reach
`said submucosa.
`
`4
`
`

`
`Layers of epithelial tissue
`’609, ’913 & Lonky ’044 Patents
`“The reason one seeks to obtain a transepithelial sample is because
`suspect cells appear at the superficial layer of the epithelium originate
`at the basal layer within the tissue. With respect to the [oral cavity,
`(Lonky ’044 Patent)] [nasopharynx, hypopharynx, pharynx, trachea,
`larynx, and the upper esophagus (’609 and ’913 Patents)], basal cells
`originate in the general area of the basement membrane
`separating the epithelial tissue from the tissue below the
`membrane known as the submucosa. In determining whether
`or not a patient has a precancerous or cancerous condition, it is
`important to reach down to the basement membrane and
`slightly therebelow because metastases may be suspected
`depending on the cellular architecture existing at just
`below or at the basement membrane through to the
`superficial layer.”
`IPR2014-00639 Ex. 1001 at 7:2-14
`IPR2014-00641 Ex. 1001 at 7:6-18
`IPR2014-00642 Ex. 1001 at 5:30-41
`
`Basement Membrane
`
`Submucosa
`
`Epithelium
`
`IPR2014-00639 Ex. 1001 at Fig. 5, 9:43-45, 10:3-4
`IPR2014-00641 Ex. 1001 at Fig. 5, 9:48-49, 9:53-10:1
`IPR2014-00642 Ex. 1001 at 4:34-37, 11:56-61
`
`5
`
`

`
`Transepithelial Oral Biopsy
`
`IPR2014-00642; Paper 6 (1999 JADA Article), Ex. C, Fig. 3
`
`6
`
`

`
`Patent Owner CDx Diagnostic Inc.’s Demonstratives for Oral Argument
`
`The CDx Patents
`U.S. Pat No. 6,676,609
`U.S. Pat No. 7,004,913
`U.S. Pat No. 6,258,044
`
`7
`
`

`
`U.S. Pat. No. 6,258,044
`
`U.S. Pat. No. 6,258,044
`
`1:. United States Patent
`I.l|'[Ik:t-" l.'t 3'.
`
`um l‘nn:m 51".:
`[HI lllltl.‘ Ur Piltlflltl
`
`US 6,258,044 B1
`‘Jul.
`
`{S-I-I
`
`:\E"I‘.-\IL\'I'US A‘q‘I] Fl-IE'I'IIUH I"U'H
`HH'I'.—\.]‘.‘i||"'h|'|I£ '['I-L«\.‘.'J."il"I|"I'I'H F.l .|.-‘H. ."iI"l",('IHa‘lI".N
`UP .-‘'I. HUIW ."il b'.l'}'t{'I'. l'!-ilfhti A
`N(}N-].-'h{'I{[{.-\']'lN{i 'I'I*I{'IlNIUUF_
`
`
`
`logic sample.
`
`The resulting
`
`IPR2014-00642 Ex. 1001 at Fig. 3, 5:5-11, 5:33-41
`IPR2014-00642 EX. 1001 at Fig. 3, 525-11, 5:33-41
`
`8
`
`

`
`U.S. Pat. Nos. 6,676,609 & 7,004,913
`
`U.S. Pat. Nos. 6,676,609 & 7,004,913
`
`my United SIEHES Patent
`HlII£'l'IhL'I‘g cl al.
`
`um l'nIc-nt 550.:
`ma llatu: ufl’at1-nt:
`
`US 6,676,609 Bl
`"Jan. I3. ZIHH
`
`‘'31 Uni“-‘rd SWW5 Patel“ um van-m .\u.:
`H''“''"her3''' 0‘ H"
`U“ '’'“‘~' "7 ""“""‘=
`
`US 7,004,913 B1
`""~""- 35- 3"m'
`
`[S-4] RI-'.'I'I~lx\(3'I'r\HI.l-I I-'l.RlJ!-EH FUR IJSE WITH
`I'INl}UH(.‘{)]'E FUR‘. H-RUSH IiI'l')]'1'iY
`
` [I is. 3 fi.Lr1l'm' nlujccl uf t|:v.1|::v.:.~u:nli::~.'c:nlln:: tn pruwidc a
`
`SUMMARY OF THE INVENTION
`It i.-'~ :1 l'unhv.;r cnhjcul mt" lhr: ].H'«.:.-'u.,-nl
`in‘-«'v.;I1l1'LH1 In |'.I]'I'.'I‘-"'lI'.1I.; a
`nun-L'n.'::rHlI'I1g a]'I1'rar;:III.-'~ wI1I'r.'h Ina;-'
`r:.'+c|i13r'
`.*i.'m1]1h:
`r;-:|1.*~'~
`EL'1.1:'|] ull 1-::".'I.;l-_-. LI-1' u :-3I.I1L1I.:I.; L'|."|jI|J1.Z1i.E‘l1 1:::-iLII].—
`
`
`r.1i.-'~aggr-::-
`nnlnlaatraljalnal apparalufi which will |'I[L'|-: up an
`g,.1ln.:v:l 3-apt:-:.'[m1;n Ht‘ lhu wlmlu Ii:-i.~:.Lu: c1|' mulaplafilir; g]..'1r|duL1r
`'=PI"1lI=1iUI=IJ4
`
` —
`
`IPR2014-00639 Ex. 1001 at Fig. 3, 5:64-67, 6:1-6
`IPR2014-00639 EX. 1001 at Fig. 3, 5264-67, 6:1-6
`IPR2014-00641 Ex. 1001 at Fig. 3, 6:1-10
`IPR2014-00641EX. 1001 at Fig. 3, 621-10
`
`9
`9
`
`

`
`Illustrative Independent Claims
`
`U.S. Pat No. 6,258,044
`
`U.S. Pat No. 6,676,609
`
`U.S. Pat No. 7,004,913
`
`1. Apparatus to obtain cells in epithelial
`tissue
`of
`the
`body
`comprising:
`transepithelial non-lacerational sampling
`apparatus to collect cells from at least two
`layers of
`said epithelial
`tissue,
`said
`transepithelial non-lacerational sampling
`apparatus comprising a brush, said brush
`comprising bristles having sufficient
`stiffness to penetrate at least said two
`layers of said epithelial tissue.
`
`1. An apparatus to be used in conjunction with an
`endoscope to examine tissue cells located within
`epithelium tissue having a surface, said apparatus
`comprising a channel extending the length of the
`endoscope;
`said apparatus comprising a rod
`passing through said channel having a distal and a
`proximal end; a retractable non-lacerational brush
`attached to the distal end of the rod, said brush
`being movable to bear against the tissue being
`examined and being controlled by said rod to
`remove tissue from a tissue area being examined,
`said brushing apparatus comprising bristles which
`exert sufficient pressure to conduct a biopsy to
`dislodge cells and pick up a specimen of the
`tissue area located below the surface of said
`epithelium tissue.
`
`IPR2014-00639 Ex. 1001 at 10:22-34.
`
`IPR2014-00641 Ex. 1001 at 10:34-48
`
`1. An apparatus to be used in conjunction with an
`endoscope to examine tissue cells located within
`glandular epithelium, said glandular epithelium
`comprising tissue at the outermost surface thereof
`and tissue area below said outermost surface, said
`apparatus comprising a channel extending the
`length of the endoscope; said apparatus comprising
`a rod passing through said channel having a distal
`and a proximal end; a retractable non-lacerational
`brush attached to the distal end of the rod, said
`brush being movable to bear against the tissue
`being examined and being controlled by said rod to
`remove tissue from a tissue area being examined,
`said brushing apparatus comprising bristles which
`exert sufficient pressure to dislodge cells and to
`pick up a specimen from said uppermost
`surface and said tissue area therebelow.
`IPR2014-00642 Ex. 1001 at 11:48-55
`
`10
`
`

`
`Illustrative Dependent Claims
`
`U.S. Pat No. 6,258,044
`
`U.S. Pat No. 6,676,609
`
`U.S. Pat No. 7,004,913
`
`4. An apparatus as set forth in claim 3, wherein
`said specimen of the tissue area comprises a
`disaggregated specimen of the whole tissue, said
`whole tissue being defined of at least glandular
`cells, plus basement membrane fragments, plus
`elements of the submucosa in the area being
`examined.
`
`3. An apparatus as set forth in claim 1, wherein
`said
`specimen
`picked
`up
`comprises
`a
`disaggregated specimen.
`
`2. Apparatus to obtain cells in epithelial
`tissue of the body according to claim 1,
`wherein said bristles collect cells from
`three layers of said epithelial tissue, said
`three layers comprising superficial,
`intermediate and basal layers, said basal
`layer separated from the submucosa by a
`basement membrane.
`
`3. Apparatus to obtain cells in epithelial
`tissue of the body according to claim 2,
`wherein said bristles of said brush have
`sufficient stiffness to penetrate said
`basement membrane and reach said
`submucosa.
`
`IPR2014-00639 Ex. 1001 at 11:56-65
`
`IPR2014-00641 Ex. 1001 at 10:40-45
`
`IPR2014-00642 Ex. 1001 at 11:62-65
`
`11
`
`

`
`Patent Owner CDx Diagnostic Inc.’s Demonstratives for Oral Argument
`
`Ground 1: The claims are not anticipated by Parasher
`U.S. Pat No. 6,676,609: Claim 1-4
`U.S. Pat No. 7,004,913: Claims 1-3
`U.S. Pat No. 6,258,044: Claims 1-8, 11-17, 23-28, 32, and 35-39
`
`12
`
`

`
`Parasher Patent
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642
`Ex. 1003 at Fig. 3, 1:18-30, 2:10-16, 2:26-29.
`
`13
`
`

`
`Parasher Patent
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642
`Ex. 1003 at Fig. 3, Abstract, 6:1-13
`
`14
`
`

`
`Parasher Patent
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642 Ex. 1003 at 2:20-40, 3:23-32, 3:61-67
`
`15
`
`

`
`Patent Owner CDx Diagnostic Inc.’s Demonstratives for Oral Argument
`
`Biopsy
`
`16
`
`

`
`PTAB Decision to Institute – ’044 Patent
`
`“We agree with Patent Owner that Parasher does not disclose expressly that its
`brush obtains tissue that includes deep epithelial layers, submucosa or connective
`tissue. But Patent Owner does not address the testimony of Dr. Kahaleh . . . .”
`
`“We accept, for the purposes of this decision, Dr. Kahaleh’s testimony that one of
`ordinary skill in the art would have understood the term ‘biopsy’ as referring to a
`tissue sample that contains fragments of epithelial tissue, basement membrane, and
`submucosa. See id. ¶ 10.”
`
`IPR2014-00642 Paper 7 at 6
`
`17
`
`

`
`PTAB Decision to Institute – ’609 and ’913 Patents
`
`We, however, agree with Patent Owner that the portion of Parasher cited by Petitioner refers to “adjacent
`tissues,” not “adjacent connective tissues,” and does not provide the example of submucosa as adjacent tissue.
`See Prelim. Resp. 4–5; Ex. 1003, 1:54–67. For that reason, Petitioner overstates what the reference discloses. Yet this does not end our
`inquiry, because the Petition provides other support for the contention that Parasher’s brush is capable of dislodging cells and picking up
`a specimen of tissue below the surface of the epithelium tissue as claimed. In particular, Petitioner asserts that Parasher’s device 1
`includes brush 9 having semi-rigid bristles 11 that permit collection, without laceration, of a tissue sample sufficient to qualify as a
`biopsy. Pet. 14–16, 21–22 (citing, inter alia, Ex. 1003, 2:12–40, 4:46–59, 5:46–57, Figs 4a–4c). Petitioner asserts, citing for
`support the Declaration of Michel Kahaleh, M.D., that a person of ordinary skill in the art would have
`understood a biopsy sample to include fragments of tissue all the way down to the submucosa, as well as
`fragments of the basement membrane. Pet. 17, 22 (citing Ex. 1010 ¶ 10). The portions of Parasher cited by Petitioner and the
`supporting evidence in the Declaration adequately support Petitioner’s assertion that Parasher’s brush 9 includes bristles that penetrate
`an epithelial layer and pick up tissue located below the surface of the epithelial tissue as required by claim 1. See Pet. 22.
`
`IPR2014-00639 Paper 8 at 11
`IPR2014-00641 Paper 7 at 9-10
`
`18
`
`

`
`“Biopsy” as defined in the art
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642 Ex. 2003
`
`19
`
`

`
`“Biopsy” as defined in the art
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642 Ex. 2004
`
`20
`
`

`
`“Biopsy” as defined in the art
`
`biopsy
`the removal and examination,
`usually microscopic, of tissue
`from the living body, performed
`to establish precise diagnosis.
`
`biopsy
`1.
`Process of removing tissue from
`living patients for diagnostic
`examination.
`2. A specimen obtained by biopsy
`
`brush biopsy
`biopsy in which cells or tissue is
`obtained by manipulating tiny
`brushes against the tissue or
`lesion in question (e.g., through a
`bronchoscope) at the desired site.
`
`brush biopsy
`biopsy obtained by passing a
`bristled catheter into a tubular or
`hollow organ to remove cells
`from suspected areas of disease.
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642 Ex. 2003, 2004
`
`21
`
`

`
`“Tissue”
`
`Tissue
`An aggregation of similarly
`specialized cells united in the
`performance of a particular
`function.
`
`Tissue
`A collection of similar cells and the
`intercellular substances surrounding
`them. There are four basic tissues in
`the body: 1) epithelium; 2) the
`connective tissues, including blood,
`bone, and cartilage; 3) muscle tissue;
`and 4) nerve tissue.
`
`Kahaleh Deposition
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642. Ex. 2003, 2004, 2005 at 11:19-12:2
`
`22
`
`

`
`“Gross Tissue”
`
`Parasher Patent
`“It would be advantageous therefore to provide an
`instrument
`that
`is capable of obtaining a brush
`cytology sample that can also be used to obtain a
`larger tissue sample for a biopsy, preferably enabling
`selection of a brush sample more dependably, and
`enabling collection of a gross tissue sample or biopsy,
`using the same tool and substantially via the same
`procedure. Such an instrument would be particularly
`useful in the diagnosis of anomalies of the pancreato-
`biliary structures, such as a malignancy presented as a
`stricture of the ducts.”
`IPR2014-00639; IPR2014-00641; IPR2014-00642
`Ex. 1003, Parasher Patent, at 2:20-26
`
`Fromowitz Deposition
`
`IPR2014-00639, Ex. 1012
`IPR2014-00641, Ex. 1012
`IPR2014-00642, Ex. 1013
`Fromowitz Dep., at 35:6-16
`
`23
`
`

`
`CDx Diagnostic’s Expert - Dr. Fromowitz
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642 Ex. 2001
`
`24
`
`

`
`CDx Diagnostic’s Expert - Dr. Fromowitz
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642 Ex. 2001
`
`25
`
`

`
`The ‘609 patent claim language
`
`U.S. Pat. No. 6,676,609 claims recite the term “biopsy”
`1. An apparatus to be used in conjunction with an endoscope to examine tissue cells located within epithelium tissue
`having a surface, said apparatus comprising a channel extending the length of the endoscope; said apparatus
`comprising a rod passing through said channel having a distal and a proximal end; a retractable non-lacerational brush
`attached to the distal end of the rod, said brush being movable to bear against the tissue being examined and being
`controlled by said rod to remove tissue from a tissue area being examined, said brushing apparatus comprising bristles
`which exert sufficient pressure to conduct a biopsy to dislodge cells and pick up a specimen of the tissue area
`located below the surface of said epithelium tissue.
`
`4. An apparatus as set forth in claim 3, wherein said specimen of the tissue area comprises a disaggregated specimen of
`the whole tissue, said whole tissue being defined of at least glandular cells, plus basement membrane fragments,
`plus elements of the submucosa in the area.
`
`26
`
`

`
`Parasher Patent
`
`Claims
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642
`Ex. 1003 at 7:11-13.
`
`27
`
`

`
`U.S. Endoscopy’s Expert - Dr. Kahaleh
`
`Kahaleh Declaration
`
`Kahaleh Deposition
`
`IPR2014-00639, Ex. 1010
`IPR2014-00641, Ex. 1010
`IPR2014-00642, Ex. 1011
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642. Ex. 2005 at 6:18-7:6.
`
`28
`
`

`
`U.S. Endoscopy’s Expert - Dr. Kahaleh
`
`Kahaleh Declaration
`
`Kahaleh Deposition
`
`IPR2014-00639, Ex. 1010; IPR2014-00641, Ex. 1010; IPR2014-00642, Ex. 1011
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642. Ex. 2005 at 25:23-26:17.
`
`29
`
`

`
`Parasher Patent
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642 Ex. 1003 at 2:1-8
`
`30
`
`

`
`U.S. Endoscopy’s Expert - Dr. Kahaleh
`
`Kahaleh Declaration
`
`Kahaleh Deposition
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642. Ex. 2005 at 21:21-22:6.
`
`IPR2014-00639, Ex. 1010; IPR2014-00641, Ex. 1010; IPR2014-00642, Ex. 1011
`
`31
`
`

`
`U.S. Endoscopy’s Expert - Dr. Kahaleh
`
`Kahaleh Declaration
`
`Kahaleh Deposition
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642. Ex. 2005 at 4:5-9.
`
`IPR2014-00639, Ex. 1010; IPR2014-00641, Ex. 1010; IPR2014-00642, Ex. 1011
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642. Ex. 2005 at 4:23-5:6
`
`32
`
`

`
`U.S. Endoscopy’s Expert - Dr. Kahaleh
`
`Kahaleh Declaration
`
`Kahaleh Deposition
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642. Ex. 2005 at 5:15-24.
`
`IPR2014-00639, Ex. 1010; IPR2014-00641, Ex. 1010; IPR2014-00642, Ex. 1011
`
`33
`
`

`
`Patent Owner CDx Diagnostic Inc.’s Demonstratives for Oral Argument
`
`Petitioner’s reliance on Dr. Fromowitz’s cross-
`examination testimony is incorrect
`
`34
`
`

`
`Dr. Fromowitz’s Testimony
`Petitioner’s Reply
`“Patent Owner’s expert, Dr. Frank Fromowitz, a
`pathologist, testified that the brush of Parasher collects
`a specimen of tissue located below the surface of the
`epithelium as required by the claims of the ‘609
`Patent:
`Q) [T]he gross tissue sample they [Parasher] are
`talking about is a similar sample that is gathered
`by the asserted patents?
`A) That you can actually see that you have
`fragments of tissue, yes.
`(Ex. 1012 at 96:13-18.)”
`IPR2014-00639, Paper 18, at 1.
`IPR2014-00641, Paper 17, at 1.
`See also IPR2014-00642, Paper 16, at 1.
`
`Fromowitz Deposition
`
`35:14-16
`
`95:24-25
`96:5-7
`
`96:13-18
`
`IPR2014-00639, Ex. 1012; IPR2014-00641, Ex. 1012; IPR2014-00642, Ex. 1013
`
`35
`
`

`
`Dr. Fromowitz’s Testimony
`Petitioner’s Reply
`“The experts agree that the type of brush biopsy in
`Parasher penetrates into the submucosa and obtains
`a full thickness sample. (Ex. 1010 at ¶ 16; Ex. 1012
`at 80:9-90:4; 95:11; 96:13-18.) The submucosa is
`located below the epithelial tissue so it is axiomatic
`that if the submucosa is reached, the layers of the
`epithelium of have been transversed. (Ex. 1012 at
`75:8-77:2; Ex. 1013.)”
`IPR2014-00639, Paper 18, at 11.
`See also IPR2014-00641, Paper 17, at 11.
`See also IPR2014-00642, Paper 16, at 9.
`
`Fromowitz Deposition
`
`81:5-9
`
`82:12-17
`
`IPR2014-00639, Ex. 1012; IPR2014-00641, Ex. 1012; IPR2014-00642, Ex. 1013
`
`36
`
`

`
`Dr. Fromowitz’s Testimony
`Petitioner’s Reply
`“The experts agree that the type of brush biopsy in
`Parasher penetrates into the submucosa and obtains
`a full thickness sample. (Ex. 1010 at ¶ 16; Ex. 1012
`at 80:9-90:4; 95:11; 96:13-18.) The submucosa is
`located below the epithelial tissue so it is axiomatic
`that if the submucosa is reached, the layers of the
`epithelium of have been transversed. (Ex. 1012 at
`75:8-77:2; Ex. 1013.)”
`IPR2014-00639, Paper 18, at 11.
`See also IPR2014-00641, Paper 17, at 11.
`See also IPR2014-00642, Paper 16, at 9.
`
`Fromowitz Deposition
`
`74:13-18
`
`75:8-20
`
`IPR2014-00639, Ex. 1012; IPR2014-00641, Ex. 1012; IPR2014-00642, Ex. 1013
`
`37
`
`

`
`Dr. Fromowitz’s Testimony
`Petitioner’s Reply
`“The experts agree that the type of brush biopsy in
`Parasher penetrates into the submucosa and obtains
`a full thickness sample. (Ex. 1010 at ¶ 16; Ex. 1012
`at 80:9-90:4; 95:11; 96:13-18.) The submucosa is
`located below the epithelial tissue so it is axiomatic
`that if the submucosa is reached, the layers of the
`epithelium of have been transversed. (Ex. 1012 at
`75:8-77:2; Ex. 1013.)”
`
`IPR2014-00639, Paper 18, at 11.
`See also IPR2014-00641, Paper 17, at 11.
`See also IPR2014-00642, Paper 16, at 9.
`
`Fromowitz Deposition
`
`93:9-11
`
`94:23-95:12
`
`IPR2014-00639, Ex. 1012; IPR2014-00641, Ex. 1012; IPR2014-00642, Ex. 1013
`
`38
`
`

`
`Dr. Fromowitz’s Testimony
`
`Fromowitz Deposition
`
`IPR2014-00639, Ex. 1012
`IPR2014-00641, Ex. 1012
`IPR2014-00642, Ex. 1013
`
`Fromowitz Dep. at 111:11-23
`
`IPR2014-00639, Ex. 1012
`IPR2014-00641, Ex. 1012
`IPR2014-00642, Ex. 1013
`
`Fromowitz Dep. at 112:8-17
`
`39
`
`

`
`Dr. Fromowitz’s Testimony
`Petitioner’s Reply
`“The experts agree that the type of brush biopsy in
`Parasher penetrates into the submucosa and obtains
`a full thickness sample. (Ex. 1010 at ¶ 16; Ex. 1012
`at 80:9-90:4; 95:11; 96:13-18.) The submucosa is
`located below the epithelial tissue so it is axiomatic
`that if the submucosa is reached, the layers of the
`epithelium of have been transversed. (Ex. 1012 at
`75:8-77:2; Ex. 1013.)”
`
`IPR2014-00639, Paper 18, at 11.
`See also IPR2014-00641, Paper 17, at 11.
`See also IPR2014-00642, Paper 16, at 9.
`
`Fromowitz Deposition
`
`112:18-113:8
`
`IPR2014-00639, Ex. 1012; IPR2014-00641, Ex. 1012; IPR2014-00642, Ex. 1013
`
`40
`
`

`
`Dr. Fromowitz’s Testimony
`Petitioner’s Reply
`“He also testified that Parasher’s brush: 1) acquires the
`same tissue sample required by the claims, (id. at 96:13-
`18), 2) penetrates the layers of the epithelium and into
`submucosa (id. at 95:6-12, 99:5-16, 99:24-100:4)
`the
`and is non-lacerational” (id. at 101:5-8). Moreover, he
`testified that Parasher’s use of the term ‘adjacent tissue’
`included submucosa. (Id. at 94:20-95:12.)”
`IPR2014-00639, Paper 18, at 7.
`IPR2014-00641, Paper 17, at 7.
`IPR2014-00642, Paper 16, at 6.
`
`Fromowitz Deposition
`
`’609 Patent
`
`41
`
`IPR2014-00639, Ex. 1012
`IPR2014-00641, Ex. 1012
`IPR2014-00642, Ex. 1013
`
`Fromowitz Dep. at 99:5-16
`
`

`
`Dr. Fromowitz’s Testimony
`Petitioner’s Reply
`“He also testified that Parasher’s brush: 1) acquires the
`same tissue sample required by the claims, (id. at 96:13-
`18), 2) penetrates the layers of the epithelium and into
`submucosa (id. at 95:6-12, 99:5-16, 99:24-100:4)
`the
`and is non-lacerational” (id. at 101:5-8). Moreover, he
`testified that Parasher’s use of the term ‘adjacent tissue’
`included submucosa. (Id. at 94:20-95:12.)”
`IPR2014-00639, Paper 18, at 7.
`IPR2014-00641, Paper 17, at 7.
`IPR2014-00642, Paper 16, at 6.
`
`Fromowitz Deposition
`
`Fromowitz Dep. at 99:24-100:4
`
`IPR2014-00639, Ex. 1012; IPR2014-00641, Ex. 1012; IPR2014-00642, Ex. 1013
`
`42
`
`Fromowitz Dep. at 112:18-113:8
`
`

`
`Dr. Fromowitz’s Testimony
`
`Petitioner’s Reply
`
`Fromowitz Deposition
`
`IPR2014-00642, Paper 16 at 10
`
`120:11-18
`
`121:4-13
`
`IPR2014-00639, Ex. 1012; IPR2014-00641, Ex. 1012; IPR2014-00642, Ex. 1013
`
`43
`
`

`
`Patent Owner CDx Diagnostic Inc.’s Demonstratives for Oral Argument
`
`Ground 1: Claims 4-11, 14-17, 24 of U.S. Patent
`6,258,044 are not anticipated by Parasher
`
`44
`
`

`
`U.S. Pat. No. 6,258,044
`
`Claims
`
`IPR2014-00642, Ex. 1001 at Figs. 3 and 4, 6:55-7:7, 11:66-12:3
`
`45
`
`

`
`’044 Patent – Petition
`
`Claim
`
`Parasher
`
`IPR2014-00642, Paper 1 at 13.
`
`46
`
`

`
`Parasher Patent
`
`IPR2014-00639; IPR2014-00641; IPR2014-00642
`Ex. 1003 at Fig. 3, 4:21-31.
`
`47
`
`

`
`Patent Owner CDx Diagnostic Inc.’s Demonstratives for Oral Argument
`
`Ground 2: ’609 claims 3 & 4 and ’913 claim 3 are not
`obvious over the combination of Parasher and
`Eisen
`
`48
`
`

`
`Eisen Patent
`
`IPR2014-00639; IPR2014-00641 Ex. 1005 at Fig. 8, 6:1-19, 11:12-25
`
`49
`
`

`
`Eisen Patent
`
`Abstract
`
`Specification
`
`IPR2014-00639; IPR2014-00641
`Ex. 1005 at Abstract, 6:1-13, 7:20-31
`
`50
`
`

`
`One cannot simply substitute the Eisen brush into the
`Parasher endoscope
`Eisen Patent, Fig. 8
`
`Parasher Patent, Fig. 3
`
`51
`
`

`
`Patent Owner CDx Diagnostic Inc.’s Demonstratives for Oral Argument
`
`Ground 2: ’044 claims 9, 10, 19 and 20 are not
`obvious over the combination of Parasher and
`Markus
`
`52
`
`

`
`’044 Patent Claims
`
`9 & 19. Apparatus as set forth in claim [5 / 18], wherein
`said bristles have a tip stiffness, and wherein the tip
`stiffness of each bristle is between 0.04 and 0.2
`lbs/inch.
`
`10 & 20. Apparatus as set forth in claim [9 /19],
`wherein said bristles have a tip stiffness, and wherein
`said bristles protrude between 0.05-0.2 inches.
`
`IPR2014-00642, Ex. 1001 at 12:16-21, 12:57-63.
`
`53
`
`

`
`Markus Patent
`
`IPR2014-00642
`Ex. 1005 at Fig. 2, 2:12-29, 4:40-55
`
`54
`
`

`
`Markus Patent
`
`IPR2014-00642 Ex. 1005 at 2:60-3:39
`
`55
`
`

`
`Markus Patent
`
`IPR2014-00642
`Ex. 1005 at Fig. 5, 4:56-5:13
`
`56