`V.
`Patent Owner CDx Diagnostics, Inc.
`
`IPR2014-00639 (U.S. Patent No. 6,676,609)
`
`IPR2014-00641 (U.S. Patent No. 7,004,913)IPR2014-00641 (U.S. Patent No. 7,004,913)
`IPR2014-00642 (U.S. Patent No. 6,258,044)
`
`Before Phillip J. Kauffman, Scott E. Kamholz and Barry L. Grossman
`Administrative Patent Judges
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`May 21, 2015
`
`
`
`Tissue Sample
`
`Superficial Layer
`
`Intermediate Layer
`
`Epithelium
`
`Basal Layer
`
`Basement Membrane
`
`
`
`SubmucosaSubmucosa
`
`See IPR2014-00642 Ex. 1010 ¶¶9-12 (Kahaleh)
`See also:
`IPR2014-00642 Ex. 1001 5:5-40, claims 1-3, 12-13,26-28, 37-39;
`IPR2014-00639 Ex. 1001 6:50-7:14, 9:43-10:13, Fig. 5, claims 1, 4;
`IPR2014-00641 Ex. 1001 7:1-18, 9:47-10:10, Fig. 5, claim 1.
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`2
`
`
`
`Fromowitz Deposition Exhibit 6
`
`IPR2014-00639 Ex. 1013
`See also
`IPR2014-00639 Ex. 1001 Fig. 5;
`IPR2014-00641 Ex. 1001 Fig. 5.
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`3
`
`
`
`Purpose of the Patents Under Review
`•
`“If all elements are in the brush biopsy, the brush biopsy of this
`invention is the equivalent of a lacerational biopsy which becomes
`
`substantially failsafe for medical diagnosis.” (IPR2014-00639 Ex. 1001substantially failsafe for medical diagnosis.”
`
`10:4-7; IPR2014-00641 Ex. 1001 10:1-4) (emphasis added).10:4-7; IPR2014-00641 Ex. 1001 10:1-4) (emphasis added).
`
`•
`
`•
`
`“It is an object of the present invention to provide an apparatus and
`method for sampling epithelial cells from the anatomy without
`the pain or injury of lacerational biopsies.” (IPR2014-00642 Ex. 1001
`4:28-30) (emphasis added).
`
`“For purposes of this patent application, the prior art scalpel
`procedure is defined as lacerational ...” (IPR2014-00639 Ex. 1001 6:21-22;
`IPR2014-00641 Ex. 1001 6:25-26; IPR2014-00642 Ex. 1001 4:55-56).
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`4
`
`
`
`‘044 Patent - Claims Under Review
`
`• Independent Claims: 1, 12, 26, and 37
`
`• Dependent Claims: 2-11, 13-17, 19, 20, 23-25,• Dependent Claims: 2-11, 13-17, 19, 20, 23-25,
`27-28, 32, 35-36, and 38-39
`
`IPR2014-00642 Institution Decision, Paper No. 7, p. 15
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`5
`
`
`
`‘044 Patent - Two Layers of Epithelial Tissue
`
`Claim 1. “. . . bristles having sufficient
`stiffness to penetrate at least said two
`
`layers of said epithelial tissue.”layers of said epithelial tissue.”
`
`Claim 26. “. . . passing a
`transipithelial non lacerational
`sampling means through the
`epithelial tissue to collect cells from
`at least two layers of said epithelial
`tissue.”
`
`Claim 37. “. . . an assemblage ofClaim 37. “. . . an assemblage of
`
`penetrating edges to penetrate at
`least said two layers of said epithelial
`tissue.”
`
`Superficial Layer
`
`Intermediate Layer
`
`Epithelium
`
`Basal Layer
`
`Basement Membrane
`
`Submucosa
`
`See IPR2014-00642 Ex. 1010 ¶¶9-12 (Kahaleh)
`See also:
`IPR2014-00642 Ex. 1001 5:5-40, claims 1-3, 12-13,26-28, 37-39;
`IPR2014-00639 Ex. 1001 6:50-7:14, 9:43-10:13, Fig. 5, claims 1, 4;
`IPR2014-00641 Ex. 1001 7:1-18, 9:47-10:10, Fig. 5, claim 1.
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`6
`
`
`
`‘044 Patent - Three Layers of Epithelial Tissue
`
`Claim 2. “. . . 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.”the submucosa by a basement membrane.”
`
`Claim 12. “. . . means to traverse said superficial,
`intermediate and basal layers and to collect cells
`from said three layers.”
`
`Claim 27. “. . . wherein said transepithelial non-
`lacerational sampling means collects cells from
`three layers of said epithelial tissue, said three
`layers comprising superficial, intermediate and
`basal layers.”
`
`Claim 38. “. . . wherein said assemblage ofClaim 38. “. . . wherein said assemblage of
`penetrating edges 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.”
`
`Superficial Layer
`
`Intermediate Layer
`
`Epithelium
`
`Basal Layer
`
`Basement Membrane
`
`Submucosa
`
`See IPR2014-00642 Ex. 1010 ¶¶9-12 (Kahaleh)
`See also:
`IPR2014-00642 Ex. 1001 5:5-40, claims 1-3, 12-13,26-28, 37-39;
`IPR2014-00639 Ex. 1001 6:50-7:14, 9:43-10:13, Fig. 5, claims 1, 4;
`IPR2014-00641 Ex. 1001 7:1-18, 9:47-10:10, Fig. 5, claim 1.
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`7
`
`
`
`‘044 Patent - Basement Membrane and Submucosa
`
`Claim 3. “. . . wherein said bristles of said
`brush have sufficient stiffness to penetrate
`said basement membrane and reach said
`
`submucosa.”submucosa.”
`Claim 13. “. . . wherein said means to
`traverse said three layers comprises
`sufficient stiffness to traverse said
`basement membrane and reach into said
`submucosa.”
`Claim 28. “. . . wherein said transepithelial
`non-lacerational sampling means
`penetrates said basement membrane.”
`
`Claim 39. “. . . wherein said assemblage ofClaim 39. “. . . wherein said assemblage of
`penetrating edges penetrates said
`basement membrane and reach said
`submucosa.”
`
`Superficial Layer
`
`Intermediate Layer
`
`Epithelium
`
`Basal Layer
`
`Basement Membrane
`
`Submucosa
`
`See IPR2014-00642 Ex. 1010 ¶¶9-12 (Kahaleh)
`See also:
`IPR2014-00642 Ex. 1001 5:5-40, claims 1-3, 12-13,26-28, 37-39;
`IPR2014-00639 Ex. 1001 6:50-7:14, 9:43-10:13, Fig. 5, claims 1, 4;
`IPR2014-00641 Ex. 1001 7:1-18, 9:47-10:10, Fig. 5, claim 1.
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`8
`
`
`
`‘609 Patent - Claims Under Review
`
`• Independent Claim: 1
`
`• Dependent Claims: 2-4• Dependent Claims: 2-4
`
`IPR2014-00639 Institution Decision, Paper No. 8, p. 15
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`9
`
`
`
`‘609 Patent
`
`Claim 1. “. . . bristles which exert
`sufficient pressure to conduct a
`biopsy to dislodge cells and pick up a
`
`specimen of the tissue area locatedspecimen of the tissue area located
`below the surface of said epithelium
`tissue.”
`
`Claim 4. “. . . 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, plusdefined of at least glandular cells, plus
`basement membrane fragments, plus
`elements of the submucosa in the
`area being examined.”
`
`Superficial Layer
`
`Intermediate Layer
`
`Epithelium
`
`Basal Layer
`
`Basement Membrane
`
`Submucosa
`
`See IPR2014-00642 Ex. 1010 ¶¶9-12 (Kahaleh)
`See also:
`IPR2014-00642 Ex. 1001 5:5-40, claims 1-3, 12-13,26-28, 37-39;
`IPR2014-00639 Ex. 1001 6:50-7:14, 9:43-10:13, Fig. 5, claims 1, 4;
`IPR2014-00641 Ex. 1001 7:1-18, 9:47-10:10, Fig. 5, claim 1.
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`10
`
`
`
`‘913 Patent - Claims Under Review
`
`• Independent Claim: 1
`
`• Dependent Claims: 2-3• Dependent Claims: 2-3
`
`IPR2014-00641 Institution Decision, Paper No. 7, p. 14
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`11
`
`
`
`‘913 Patent
`Claim 1. “. . . said glandular
`epithelium comprising
`
`tissue at the outermosttissue at the outermost
`surface thereof and tissue
`area below said outermost
`surface . . . bristles which
`exert sufficient pressure to
`dislodge cells and to pick up
`
`a specimen from saida specimen from said
`uppermost surface and said
`tissue area therebelow.”
`
`See IPR2014-00642 Ex. 1010 ¶¶9-12 (Kahaleh)
`See also:
`IPR2014-00642 Ex. 1001 5:5-40, claims 1-3, 12-13,26-28, 37-39;
`IPR2014-00639 Ex. 1001 6:50-7:14, 9:43-10:13, Fig. 5, claims 1, 4;
`IPR2014-00641 Ex. 1001 7:1-18, 9:47-10:10, Fig. 5, claim 1.
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`12
`
`Superficial Layer
`
`Intermediate Layer
`
`Epithelium
`
`Basal Layer
`
`Basement Membrane
`
`Submucosa
`
`
`
`Parasher
`
`IPR2014-00642 Ex. 1003 Abstract
`(highlights added)
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`13
`
`
`
`Parasher Cont’d
`• Parasher discloses a brush capable of taking a sample of
`tissue sufficient to qualify as a biopsy
`
`IPR2014-00642 Ex. 1003 2:10-35
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`14
`
`
`
`Parasher Cont’d
`• The gross tissue sample in Parasher is the
`
`same as the tissue sample taken with biopsysame as the tissue sample taken with biopsy
`forceps (i.e., a lacerational biopsy).
`
`(IPR2014-00642 Ex. 1013 pp. 26, 99-100; IPR2014-00642 Ex. 1003 2:2-6)
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`15
`
`
`
`Parasher Cont’d
`
`IPR2014-00642 Ex. 1003 1:40-45
`
`IPR2014-00642 Ex. 1003 2:2-6
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`16
`
`
`
`Parasher Cont’d
`
`. . .
`
`IPR2014-00642 Ex. 1003 2:12-25
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`17
`
`
`
`Parasher Cont’d
`
`IPR2014-00642 Ex. 1003 2:30-35
`
`IPR2014-00642 Ex. 1003 2:41-43
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`18
`
`
`
`Parasher Cont’d
`
`IPR2014-00642 Ex. 1003 3:7-9
`
`IPR2014-00642 Ex. 1003 3:23-28
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`19
`
`
`
`Parasher Cont’d
`
`IPR2014-00642 Ex. 1003 3:30-32
`
`IPR2014-00642 Ex. 1003 3:63-67
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`20
`
`
`
`Parasher Cont’d
`
`IPR2014-00642 Ex. 1003 6:5-10
`
`IPR2014-00642 Ex. 1003 6:15-17
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`21
`
`
`
`Declaration and Deposition of Dr. Michael
`Kahelah
`• “[T]he biopsy sample will include not only
`
`fragments of epithelial tissue but alsofragments of epithelial tissue but also
`fragments of the submucosa.” IPR2014-00642 Ex.
`1011 ¶10.
`• “A biopsy is a specimen that is taken from an
`epithelium, the area just below the epithelium
`
`with a device, so it typically includes mucosawith a device, so it typically includes mucosa
`and submucosa.” IPR2014-00642 Ex. 2005 p. 8.
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`22
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 24
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`23
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 26
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`24
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 29
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`25
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 pp. 45-46
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`26
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 46
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`27
`
`
`
`Fromowitz Depo
`
`* * *
`
`IPR2014-00642 Ex. 1013 pp. 48-49
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`28
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 52
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`29
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 pp. 69-70
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`30
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 72
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`31
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 75;
`IPR2014-00639 Ex. 1013
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`32
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 96
`
`IPR2014-00642 Ex. 1003 2:20-26
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`33
`
`
`
`Fromowitz Depo
`
`
`
`IPR2014-00642 Ex. 1013 p. 98IPR2014-00642 Ex. 1013 p. 98
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`34
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 98;
`IPR2014-00642 Ex. 1003 3:23-28;
`IPR2014-00639 Ex. 1013.
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`35
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 99;
`IPR2014-00639 Ex. 1013
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`36
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 pp. 99-100;
`IPR2014-00642 Ex. 1003 2:20-26;
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`37
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 108 (Redirect by
`Patent Owner)
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`38
`
`
`
`Fromowitz Depo
`
`IPR2014-00642 Ex. 1013 p. 109 (Redirect by
`Patent Owner)
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`39
`
`
`
`Kahaleh Depo
`
`IPR2014-00642 Ex. 2005 p. 27
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`40
`
`
`
`Declaration of Dr. Michael Kahaleh
`
`In my experience, physicians use a variety of
`tools including brushes to obtain biopsy
`
`samples. It is my further experience thatsamples. It is my further experience that
`when a physician uses a brush to obtain such
`a biopsy sample, the brush will obtain a
`variety of cells including tissue located below
`the top surface of the epithelium including
`
`the basement membrane and submucosa.the basement membrane and submucosa.
`
`IPR2014-00642 Ex. 1011 ¶ 16 (emphasis added).
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`41
`
`
`
`The Experts Agree
`
`Kahaleh’s Declaration
`
`Fromowitz’s Cross Examination
`
`[W]hen a physician uses a brush to obtain[W]hen a physician uses a brush to obtain
`
`such a biopsy sample, the brush will obtain a
`variety of cells including tissue located below
`the top surface of the epithelium including the
`basement membrane and submucosa.
`
`
`
`IPR2014-00642 Ex. 1011 ¶ 16 (emphasis added).IPR2014-00642 Ex. 1011 ¶ 16 (emphasis added).
`
`Q) So when you see gross tissue sample orQ) So when you see gross tissue sample or
`
`biopsy being gathered by a brush, a gross
`tissue sample being gathered by a brush . . .
`includes, in at least some instances, into the
`submucosa?
`A) I would say in some instances, yes.
`
`IPR2014-00642 Ex. 1013 pp. 99-100 (emphasis added).
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`42
`
`
`
`The Experts Agree
`
`IPR2014-00642 Ex. 1013 pp. 86-87
`(Fromowitz)
`
`IPR2014-00642 Ex. 2005 pp. 27-28
`(Kahaleh)
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`43
`
`
`
`Dictionary Definitions
`
`IPR2014-00642 Ex. 2004 pp. 2, 4
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`44
`
`
`
`Dictionary Definitions
`
`IPR2014-00642 Ex. 2003 pp. 2, 4
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`45
`
`
`
`Anticipation
`
`• ‘044 Patent: Claims 1-17, 19, 20, 23-28, 32 and
`
`35-39 are anticipated by Parasher35-39 are anticipated by Parasher (IPR2014-00642
`Institution Decision, Paper No. 7, p. 15)
`• ‘609 Patent: Claims 1-4 are anticipated by
`Parasher (IPR2014-00639 Institution Decision, Paper No. 8, p. 15)
`• ‘913 Patent: Claims 1-3 are anticipated by
`
`ParasherParasher (IPR2014-00641 Institution Decision, Paper No. 7, p. 14)
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`46
`
`
`
`Obviousness
`
`• ‘044 Patent: Claims 9, 10, 19 and 20 are
`
`obvious over Parasher and Markusobvious over Parasher and Markus (IPR2014-00642
`Institution Decision, Paper No. 7, p. 15)
`• ‘609 Patent: Claims 3 and 4 are obvious over
`Parasher and Eisen (IPR2014-00639 Institution Decision, Paper No.
`8, p. 15)
`
`• ‘913 Patent: Claim 3 are obvious over Parasher• ‘913 Patent: Claim 3 are obvious over Parasher
`and Eisen (IPR2014-00641 Institution Decision, Paper No. 7, p. 14)
`
`IPR2014-00639
`IPR2014-00641
`IPR2014-00642
`
`47