Paper _____
`
` Filed: May 7, 2014
`
`
`Filed on behalf of: The Board of Trustees of the
`
`
` Leland Stanford Junior University
`
`
`By: R. Danny Huntington, Lead Counsel
`
`Sharon E. Crane, Ph.D., Backup Counsel
`
`Rothwell, Figg, Ernst & Manbeck, P.C.
`607 14th Street, N.W., Suite 800
`
`
`Washington, DC, 20005
`
`dhuntington@rfem.com
`
`scrane@rfem.com
`
`Main Telephone: (202) 783-6040
`
`Main Facsimile: (202) 783-6031
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________
`
`
`
`
`
`SEQUENOM, INC.
`Petitioner,
`
`v.
`
`THE BOARD OF TRUSTEES OF
`THE LELAND STANFORD JUNIOR UNIVERSITY
`Patent Owner.
`____________________
`
`Case IPR2013-00390
`Patent 8,195,415
`___________________
`
`PATENT OWNER RESPONSE
`
`SEQUENOM EXHIBIT 1020
`Sequenom v. Stanford
`IPR2014-00337
`
`

`
`TABLE OF CONTENTS
`
`INTRODUCTION ............................................................................................... 1
`I.
`II. THE FAN ’415 PATENT .................................................................................... 1
`III. CLAIM INTERPRETATION .......................................................................... 2
`A. Windows of Defined Length ............................................................................ 3
`1. The Fan ’415 Patent Examples Use “Windows” of Equal Length ............... 4
`2. The Fan ’415 Patent Explicitly States “Windows” Are of Equal Length ..... 5
`3. Predefined Subsections of a Chromosome Are of Equal Length.................. 7
`4. The Board’s Interpretation in the ’922 Interference Is Unduly Broad .......... 8
`B. Sliding Window of a Predetermined Length .................................................. 11
`IV. LO II DOES NOT ANTICIPATE THE FAN ’415 PATENT CLAIMS .......... 13
`A. Windows Are Distinct from Chromosomal Regions ..................................... 13
`1. Windows in the Fan ’415 Patent Are a Tool USED TO TEST
` for Aneuploidy ............................................................................................ 14
`2. Chromosomal Regions in Lo II Are BEING TESTED
` for Aneuploidy ............................................................................................. 15
`3. The Board’s Decision in the ’922 Interference Improperly
` Attributes Additional Functions to Windows of Defined Length ............... 17
`B. The Lo II Normalization Method Shows Windows of
` Defined Length Are Not Disclosed ................................................................ 18
`C. Lo II Does Not Enable the Claim Term “Windows of Defined Length” ...... 19
`1. Lo II Does Not Contain Any Working Examples ....................................... 20
`2. Lo II Does Not Provide Any Guidance ....................................................... 20
`3. Undue Experimentation Is Required to Make and Use
` “Windows of Defined Length” Based on the Lo II Disclosure .................... 21
`V. LO II IN COMBINATION WITH WANG DOES NOT
` RENDER CLAIMS 13, 16, OR 17 OBVIOUS ................................................. 22
`
`
`
`i
`
`

`
`A. The Combination of Wang and Lo II Does Not Disclose
` a “Sliding Window a Predetermined Length” ................................................ 22
`B. The “Windows” Disclosed in Wang Are a Region
` Being Analyzed for Abnormal Distribution, and NOT
` a Subset of that Region ................................................................................... 24
`C. Wang Does Not Disclose the “Second Mean” of Claim 13, step (d) ............. 26
`VI. LO II AND WANG IN COMBINATION WITH HILLIER
` AND/OR SMITH DOES NOT RENDER CLAIM 17 OBVIOUS ................... 27
`VII. LO I DOES NOT DISCLOSE THE CONCEPT OF “WINDOWS” ............. 29
`VIII. LO II IS NOT PRIOR ART TO THE FAN ’415 PATENT .......................... 29
`A. Background ..................................................................................................... 31
`B. Collaboration with Dr. Yair Blumenfeld ........................................................ 32
`C. Conception ...................................................................................................... 33
`D. Reduction to practice ...................................................................................... 33
`1. Sequencing samples from females carrying non-aneuploid
` fetuses confirmed the conception by Drs. Fan and Quake ......................... 33
`2. Sequencing samples from females carrying either aneuploid
` or non-aneuploid fetuses was an actual reduction to practice
` by Drs. Fan and Quake ................................................................................ 36
`3. The drafts of the PNAS paper evidence the reduction to
` practice by Drs. Fan and Quake .................................................................. 38
`4. The Draft Manuscripts Disclose “Sliding Windows”
` and “Windows of Defined Length .............................................................. 60
`IX. CONCLUSION ................................................................................................. 60
`
`
`
`
`ii
`
`

`
`TABLE OF AUTHORITIES
`
`
`Cases(cid:3)
`Amgen, Inc. v. Hoescht Marion Roussel, Inc.,
`314 F.3d 1313, 1354 (Fed. Cir. 2003). .......................................................... 19
`Berges v. Gottstein,
`618 F.2d 771, 776 (CCPA 1980). .................................................................. 31
`Blicharz v. Hays,
`496 F.2d 603 (CCPA 1974) ........................................................................... 30
`Blicharz v. Hays,
`496 F.2d 603, 606 (CCPA 1974) ................................................................... 30
`Breuer v. DeMarinis,
`558 F.2d 22, 29 (CCPA 1977), ...................................................................... 31
`Clearvalue, Inc. v. Pearl River Polymers, Inc.,
`668 F.3d 1340, 1344 (Fed. Cir. 2012) ........................................................... 13
`Cooper v. Goldfarb,
`154 F.3d 1321 (Fed. Cir. 1998) ..................................................................... 30
`Depuy Spine, Inc. v. Medtronic Sofamor Danek, Inc.,
`567 F.3d 1314, 1326 (Fed. Cir. 2009). .......................................................... 27
`Graham v. John Deere Co.,
`383 U.S. 1, 17-18 (1966). .............................................................................. 22
`Hologic, Inc. v. SenoRx, Inc.,
`639 F.3d 1329, 1338 (Fed. Cir. 2011) ............................................................. 3
`In re Fine,
` 837 F.2d 1071, 1076 (Fed. Cir. 1988). .......................................................... 22
`In re Gurley,
`27 F.3d 551, 553 (Fed. Cir. 1994). ................................................................ 27
`In re Kubin,
`561 F.3d 1351, 1355 (Fed. Cir. 2009) ........................................................... 22
`In re Scheiber,
`587 F..2d 59, 61 – 62 (CCPA 1978); ............................................................. 30
`In re Spiller,
`500 F.2d 1170, 1178 (CCPA 1974). .............................................................. 30
`In re Stemptel,
`
`
`
`iii
`
`

`
`241 F.2d 755, 760 (CCPA 1957) ................................................................... 30
`In re Suitco Surface,
`603 F.3d 1255, 1260 (Fed. Cir. 2010). ............................................................ 2
`In re Wands,
` 858 F.2d 731, 737 (Fed. Cir. 1988). .............................................................. 20
`InnovaPure Water, Inc. v. Safari Water Filtration Sys., Inc.,
`381 F.3d 1111, 1119 (Fed. Cir. 2004). ............................................................ 3
`Irdeto Access, Inc. v. Echostar Satellite Corp.,
` 383 F.3d 1295, 1303 (Fed. Cir. 2004) ............................................................. 3
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398, 418 (2007). ............................................................................. 27
`Mahurkar v. CR Bard, Inc.,
`79 F.3d 1572, 1578 (Fed. Cir. 1996) ............................................................. 30
`Philips v. AWH Corp.,
`415 F.3d 1303, 1314 (Fed. Cir. 2005). ............................................................ 3
`Price v. Symsek,
`988 F.2d 1187 (Fed. Cir. 1993) ..................................................................... 30
`Schriber-Schroth Co. v. Cleveland Trust Co.,
` 311 U.S. 211, 217 (1940) ................................................................................ 2
`Wang Labs., Inc. v. Am. Online, Inc.,
`
` 197 F.3d 1377, 1382 (Fed. Cir. 1999) ............................................................. 3
`Statutes(cid:3)
`
`35 U.S.C. §112, ¶4. .................................................................................................. 14
`Regulations(cid:3)
`
`37 C.F.R. §42.100(b). ................................................................................................ 3
`
`
`
`
`
`
`iv
`
`

`
`I.
`
`INTRODUCTION
`
`Sequenom, Inc. (“Sequenom”) filed a Petition to Institute Inter Partes
`
`Review (“the Petition”) of U.S. Patent No. 8,195,415 (“the Fan ’415 patent”), and
`
`the Patent Trial and Appeal Board (“the Board”) granted Sequenom’s Petition.
`
`However, Sequenom’s allegations of invalidity are meritless, and the Board should
`
`deny Sequenom’s grounds of challenge.
`
`The Fan ’415 patent claims a method for detecting fetal aneuploidy by using
`
`windows of an equal length to normalize data, and thus eliminate the over- or
`
`under- representation of a particular chromosome that is due to a factor other than
`
`aneuploidy. In order to effectively conduct this normalization, these windows
`
`must be of an equal length. In fact, the Fan ’415 patent contemplates only the use
`
`of windows of equal length, and that is how the claim should be construed.
`
`Sequenom heavily relies on Lo II as the basis for its invalidity challenges.
`
`But Lo II is not prior art to the Fan ’415 patent. The Lo II also does not disclose
`
`the claim element “windows of defined length” as that term is properly construed.
`
`Accordingly, Sequenom’s invalidity contentions instituted in the IPR, which are all
`
`derived from the Lo II reference, must fail.
`
`II. THE FAN ’415 PATENT
`
`
`
`“Windows of defined length” and a “sliding window of a predetermined
`
`length” are described in the Fan ’415 patent specification as units of defined, equal
`
`
`
`1
`
`

`
`length that cover specific informative regions along the chromosomes. (Ex. 2117, ¶
`
`38). By counting sequence tags within a series of predefined windows of equal
`
`length along different chromosomes, an improved, statistically significant
`
`determination of fetal aneuploidy can be made because the windows eliminate the
`
`over- or under- representation of a particular chromosome that is due to a bias,
`
`such as G/C content bias, and not due to aneuploidy. (Ex. 2117, ¶¶ 39 - 40). The
`
`Fan ’415 patent provides a detailed description on the use of windows of defined
`
`length or a sliding window of a predetermined length to correct for a non-uniform
`
`distribution of sequence tags. (Ex. 2117, ¶¶ 39 - 50). Importantly, and as discussed
`
`in detail below, the description in the Fan ’415 patent makes it clear that the
`
`windows utilized with the claimed method are all of an equal length.
`
`III. CLAIM INTERPRETATION
`
`In Inter Partes Review, “a claim in an unexpired patent shall be given its
`
`broadest reasonable construction in light of the specification of the patent in which
`
`it appears.” 37 C.F.R. §42.100(b). However, the broadest reasonable construction
`
`rubric does not give an unfettered license to interpret claims to embrace anything
`
`remotely related to the claimed invention. In re Suitco Surface, 603 F.3d 1255,
`
`1260 (Fed. Cir. 2010). Claims should be read light of the specification and
`
`teachings in the underlying patent. Id. (citing Schriber-Schroth Co. v. Cleveland
`
`Trust Co., 311 U.S. 211, 217 (1940). The construction of a claim term should be
`
`
`
`2
`
`

`
`limited where “the specification, including the figures, consistently and
`
`exclusively” disclose only one embodiment, and “that is clearly what the
`
`inventors…of the patent conceived of.” Hologic, Inc. v. SenoRx, Inc., 639 F.3d
`
`1329, 1338 (Fed. Cir. 2011); See also, Irdeto Access, Inc. v. Echostar Satellite
`
`Corp., 383 F.3d 1295, 1303 (Fed. Cir. 2004); Wang Labs., Inc. v. Am. Online, Inc.,
`
`197 F.3d 1377, 1382 (Fed. Cir. 1999) (limiting the claim term "frame" to
`
`character-based protocol, even though "frame," used generally, could also refer to
`
`bit-mapped displays, because the specification described and enabled only systems
`
`using character-based protocol). The claims themselves also provide substantial
`
`guidance as to the meaning of particular claim terms. Philips v. AWH Corp., 415
`
`F.3d 1303, 1314 (Fed. Cir. 2005). Moreover, “all claim terms are presumed to
`
`have meaning in a claim.” InnovaPure Water, Inc. v. Safari Water Filtration Sys.,
`
`Inc., 381 F.3d 1111, 1119 (Fed. Cir. 2004).
`
`A. Windows of Defined Length
`
`Sequenom proposes the claim term “window” be interpreted to mean “a
`
`
`
`predefined subsection of a chromosome.” (Paper 1, p. 10). In the Decision to
`
`Institute, the Board interpreted the term “window” to mean “a predefined
`
`subsection of a chromosome of sufficient length to allow determination of an
`
`abnormal chromosome distribution, if present, based on the number of sequence
`
`tags mapping to that chromosomal subsection.” (Paper 7, p. 7-8). However, the
`
`
`
`3
`
`

`
`Board’s interpretation requires clarification for two reasons. First, the Board’s
`
`construction does not take into account the full claim term, which is “windows of
`
`defined length.” The incorporation of the additional term “of defined length”
`
`clarifies that the claimed windows (plural) are of a particular, fixed length
`
`(singular) as they are applied across a chromosome in an experiment. (Ex. 2117, ¶
`
`53). Second, the claim term should be interpreted to refer to windows of equal
`
`length because the entirety of the description in the Fan ’415 patent specification
`
`makes it clear that the disclosed windows are of equal length in a given
`
`experiment. (Ex. 2117, ¶¶ 54 - 69).
`
`
`
`1. The Fan ’415 Patent Examples Use “Windows” of Equal Length
`
`
`The portions of the Fan ’415 patent specification, including the examples
`
`and figures, that discuss the use of windows make it clear that the windows are all
`
`of equal length in a given experiment. (Ex. 2117, ¶ 55 - 59). For instance,
`
`Example 4 of the Fan ’415 patent notes the length of each chromosome is divided
`
`into windows of fixed width, e.g., 50 kb, and at no place suggests that window
`
`width can be varied within a given experiment. (Ex. 2117, ¶ 56). Even
`
`Sequenom’s expert, Dr. Gabriel, agrees that Example 4 only uses windows of fixed
`
`length, and that it does not suggest window length can be varied within a given
`
`experiment. (Ex. 2114, 28:10-29:2; Ex. 2001, 19:9-21). Example 8 also describes
`
`using windows of fixed width to calculate, and correct for, G/C content bias. (Ex.
`
`
`
`4
`
`

`
`2117, ¶ 57). Again, Dr. Gabriel agrees, and even admits that to assign weight
`
`based on G/C content equal sized windows need to be compared. (Ex. 2114, 29:3-
`
`14, 30:10-21; Ex. 2001, 21:4 – 22:10). Example 10, the only other example
`
`describing the use of windows, also discloses using fixed windows of 50 kb, and
`
`Dr. Gabriel again admits the window length is not varied within a single
`
`experiment. (Ex. 2117, ¶ 58; Ex. 2114, 29:15-21; Ex. 2001, 22:18 – 23:4). The
`
`Figures of the Fan ’415 patent demonstrate data that is obtained using windows of
`
`equal length. For example, Figures 1 and 10 shows the results from using
`
`windows of equal length. (Ex. 2117, ¶¶ 46, 50). The description for Figure 9 also
`
`notes that chromosome is divided into 50 kb windows, and does not suggest that
`
`the length of these windows varies. (Ex. 2117, ¶ 59).
`
`2. The Fan ’415 Patent Explicitly States “Windows” Are of Equal
`Length
`
`
`Sequenom selectively cites certain portions of the Fan ’415 patent
`
`
`
`specification to support its interpretation of the claim term “windows.”1 (Ex. 2117,
`
`¶ 60; Paper 1, p. 9-10). However, when read in context it is clear the portions cited
`
`by Sequenom are referring to windows of equal length. (Ex. 2117, ¶¶ 60 - 66).
`
`For example, Sequenom cites part of sentence that states, “a number of windows of
`
`defined length are created along a chromosome…” (Paper 1, p. 9-10). But
`
`Sequenom omits the first clause of this sentence which reads, “[t]his is explained
`
`1 Again, the full term to be construed should be “windows of defined length.”
`5
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`
`
`

`
`in detail below.” (Ex. 2117, ¶ 62 - 63). Inclusion of that clause in construing the
`
`claim term “windows of defined length” is important because it informs a person
`
`of ordinary skill in the art that the concept of using windows of defined length is
`
`described in greater detail below. (Ex. 2117, ¶ 63). In addition, this sentence is the
`
`only place in the Fan ’415 patent where the exact claim term “a number of
`
`windows of defined length” appears. (Ex. 2117, ¶ 62). Thus, it is important to give
`
`full context to that claim term by interpreting it with reference to the greater
`
`“detail” that is found below. (Ex. 2117, ¶¶ 63 - 64).
`
`
`
`A person of ordinary skill in the art reading the Sequenom cited sentence in
`
`its proper context would understand the additional “detail” is found in the second
`
`to last sentence of the paragraph. (Ex. 2117, ¶¶ 62 - 64). That sentence states,
`
`“[b]y counting sequence tags within a series of predefined windows of equal
`
`lengths along different chromosomes, more robust and statistically significant
`
`results may be obtained.” (Ex. 2117, ¶ 64) (Ex. 1001, 4:61-64) (emphasis added).
`
`When these sentences are read in conjunction, a person of ordinary skill in the art
`
`would understand that the “windows of defined length” are in fact “predefined
`
`windows of equal length.” Id.
`
`
`
`Sequenom also cites a passage from the Fan ’415 patent stating, “[e]ach
`
`autosome (chr. 1 – 22) is computationally segmented into contiguous, non-
`
`overlapping windows.” (Paper 1, p. 9). The Board also referred to this portion to
`
`
`
`6
`
`

`
`support its interpretation. (Paper 7, p. 8). However, this passage is in the
`
`paragraph immediately following the explicit language defining windows to be of
`
`equal length. (Ex. 2117, ¶ 65 - 66). Thus, a person of ordinary skill in the art
`
`would understand that this is also a reference to windows of equal length. Id.
`
`3. Predefined Subsections of a Chromosome Are of Equal Length
`
`
`The Board interpreted the term “windows” to be a “predefined subsection of
`
`
`
`
`a chromosome…” and supports this interpretation by citing to a portion of the Fan
`
`’415 patent specification that uses that term. (Paper 7, p.8). However, the full
`
`sentence states “[b]y analyzing sequence tag density in predefined subsections of
`
`chromosomes (e.g., 10 to 100 kb windows), a normalization constant can be
`
`calculated, and chromosomal subsections quantified (e.g., 21q22.2).” (Ex. 1001, 4:
`
`9-12) (emphasis added). Accordingly, a person of ordinary skill in the art would
`
`understand that the purpose of using predefined subsections of a chromosome is to
`
`calculate a normalization constant. (Ex. 2117, ¶ 68). In the Fan ’415 patent, the
`
`normalization constant is calculated by taking the representative number of
`
`sequence tags per window of equal length. (Ex. 2117, ¶ 38 – 50, 68). Even Dr.
`
`Gabriel agrees the normalization constant in the Fan’415 patent is calculated using
`
`windows of equal length. (Ex. 2114, 22:20 – 23:2). Dr. Gabriel could not identify
`
`anywhere in the Fan ’415 patent where the normalization constant was calculated
`
`
`
`7
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`

`
`using windows of unequal length. (Ex. 2114, 24:20-25:3). Thus, the Board cited
`
`disclosure also requires the windows to be of equal length. (Ex. 2117, ¶ 69).
`
`4. The Board’s Interpretation in the ’922 Interference Is Unduly Broad
`
`
`The Fan ’415 patent is involved in Interference No. 105,922 (“the ’922
`
`interference”). (Ex. 2117, ¶ 70). The Board issued a Decision on Motions in the
`
`’922 interference that included an erroneous interpretation of the claim term
`
`“windows.” (Ex. 2117, ¶ 71; Ex. 2116). The Board’s decision incorrectly
`
`truncated the claim term “windows of defined length,” and misinterpreted that term
`
`to encompass windows of unequal length. (Ex. 2117, ¶ 71).
`
`In reaching its interpretation, the Board in the ’922 interference unduly
`
`minimized the disclosure of the Fan ’415 patent by indicating that only “portions”
`
`of the Fan ’415 patent discuss windows of equal length. (Ex. 2117, ¶ 73; Ex. 2116,
`
`p. 15). But there are not simply “portions” of the Fan ’415 patent that discuss
`
`windows of equal length, the specification only discusses windows of equal length.
`
`(Ex. 2117, ¶¶ 55 – 69, 74). The Board also appears to have ignored that “windows
`
`of defined length” are “predefined windows of equal length” as explained in the
`
`specification. (Ex. 2117, ¶¶ 60 – 66, 72). Given these disclosures, a person of
`
`ordinary skill in the art would understand that the windows of defined length
`
`disclosed and claimed in the Fan ’415 patent are of an equal length in a given
`
`experiment. (Ex. 2117, ¶ 55 – 69, 74).
`
`
`
`8
`
`

`
`The Board’s Decision in the ’922 interference also overlooks that there is no
`
`suggestion in the Fan ’415 patent that the windows can be of unequal length. (Ex.
`
`2117, ¶ 80). Even Dr. Gabriel admits that the Fan ’415 patent does not disclose
`
`using windows of unequal length. (Ex. 2001, 17:5-11; Ex. 2114, 32:21-37:3).
`
`Thus, a person of ordinary skill in the art would not understand the claims of the
`
`Fan ’415 patent to encompass the use of windows of unequal length given that
`
`there is no such disclosure in the specification. (Ex. 2117, ¶ 80).
`
`The Board also stated that no evidence had been put forth by Fan in the ’922
`
`interference to show that a person of ordinary skill in the art would have inherently
`
`known that the windows must be of equal length. (Ex. 2116, p. 14). But as Dr.
`
`Detter explains, a person of ordinary skill in the art would have known that in
`
`order to make the normalization method of the Fan ’415 patent work, the windows
`
`must be of equal length. (Ex. 2117, ¶¶ 75 - 79). If windows of unequal length are
`
`used then it is no longer possible to directly compare information obtained from
`
`one window to another. Id. Thus, one is no longer able to determine whether a
`
`particular window contains more sequence tags than another because it is on an
`
`aneuploid chromosome, or because it has, for example, a high G/C content. (Ex.
`
`2117, ¶¶ 77 - 78). Moreover, these biases cannot be effectively accounted for
`
`through the use of windows of unequal length because a weight cannot be
`
`accurately assigned to sequence tags associated with unequal length windows. Id.
`
`
`
`9
`
`

`
`Accordingly, windows of unequal length will not provide statistically significant
`
`results because there is no ability to directly compare the contents of one window
`
`to another. (Ex. 2117, ¶¶ 75 - 79).
`
`In the ’922 interference Decision, the Board noted that while the use of
`
`windows of equal length will yield “more robust and statistically significant
`
`results,” windows of unequal length could also be used “though with less robust
`
`results.” (Ex. 2116, p. 16). But the Board’s conclusion is not supported by
`
`evidence, and is an improper assumption that utilizing windows of unequal length
`
`will permit “less robust” to be obtained. (Ex. 2117, ¶¶ 81 - 83). Moreover, the
`
`’922 Interference Board ignores that the use of windows of equal length yields
`
`“more robust and statistically significant results.” (Ex. 2116, p. 16) (emphasis
`
`added). The two concepts are linked, and, as discussed above, windows of equal
`
`length provide statistically significant results, but windows of unequal length do
`
`not. (Ex. 2117, ¶¶ 75 – 83).
`
`The Board also improperly attributed additional functions to the windows of
`
`defined length that are disclosed in the Fan ’415 patent. (Ex. 2116, p. 17). The
`
`only purpose for using windows in the Fan ’415 patent is to normalize data. (Ex.
`
`2117, ¶ 84). Any other benefit that results from using windows of defined, equal
`
`length to detect fetal aneuploidy is incidental to this purpose. (Ex. 2117, ¶ 85).
`
`
`
`
`
`10
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`

`
`B. Sliding Window of a Predetermined Length
`
`Sequenom proposed the claim term “sliding window” be construed as
`
`
`
`“contiguous, overlapping or non-overlapping, predefined subsections of a
`
`chromosome.” (Paper 1, p. 10). The Board again largely accepted Sequenom’s
`
`proposed interpretation, and construed “sliding window” to mean “a contiguous,
`
`overlapping or non-overlapping, predefined subsection of a chromosome of
`
`sufficient length to allow determination of an abnormal chromosome distribution,
`
`if present, based on the number of sequence tags mapping to that chromosomal
`
`subsection.” However, the Board’s construction of “sliding window” also requires
`
`clarification based on the full claim term in Claim 13, and that full term should be
`
`interpreted as a sliding window of a predetermined, equal length.
`
`Sequenom again proposes to interpret a truncated version of the claim term.
`
`(Ex. 2117, ¶¶ 86 - 87). Inclusion of the additional words of the claim term “of a
`
`predetermined length,” emphasizes that the claims refer to the use of a sliding
`
`window that remains fixed at a particular, preselected length in a given experiment.
`
`Id. Construing the term this way is also consistent with the Fan ’415 patent
`
`specification, and the purpose of the sliding window. Id. Moreover, to find that the
`
`predetermined length of a sliding window has multiple lengths, i.e., unequal
`
`lengths, in a given experiment would contradict the plain language used in the
`
`
`
`11
`
`

`
`claim. Id. Accordingly, the claim term “sliding window of a predetermined
`
`length,” should be interpreted to be fixed, equal length. (Ex. 2117, ¶ 88).
`
`The Fan ’415 patent provides further details on the use of a sliding window.
`
`For example, the Fan ’415 patent notes that “an arbitrary sliding window of 50 kb
`
`[was applied] across each chromosome.” (Ex. 1001, 17:10-13). Accordingly, a
`
`person of ordinary skill would understand that the sliding window applied was a
`
`fixed length of 50 kb. (Ex. 2117, ¶ 89). In other words, the size of the sliding
`
`window applied across the chromosomes does not vary. Id. Example 4 of the Fan
`
`’415 patent also makes clear that the sliding window disclosed in that example is
`
`applied across the chromosome in static, 50 kb increments. (Ex. 2117, ¶ 90). Thus,
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`the sliding window is actually a number of windows of a defined 50 kb length. Id.
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`
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`A person of ordinary skill in the art would also know that the claimed
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`“sliding window of a predetermined length” is of a fixed, equal length because the
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`sliding window is used to correct for non-uniform distribution of sequence tags,
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`i.e., it is also used to normalize data. (Ex. 2117, ¶¶ 91 - 92). The only method of
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`data normalization disclosed in the Fan ’415 patent utilizes windows of equal
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`length applied across informative regions of a chromosome. The Fan ’415 patent
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`also does not suggest that the length of a sliding window can vary within a given
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`experiment, and a person of ordinary skill in the art would understand that once the
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`width of the window is chosen, it remains fixed for a given experiment and does
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`not vary. (Ex. 2117, ¶ 93).
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`IV. LO II DOES NOT ANTICIPATE THE FAN ’415 PATENT CLAIMS
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`Anticipation requires a prior art reference to disclose every limitation of the
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`claimed invention, either expressly or inherently. Clearvalue, Inc. v. Pearl River
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`Polymers, Inc., 668 F.3d 1340, 1344 (Fed. Cir. 2012) Claims that depend from a
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`prior claim incorporate all of the limitations of the prior claim. 35 U.S.C. §112, ¶4.
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`A. Windows Are Distinct from Chromosomal Regions
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`Sequenom alleges that Lo II discloses using chromosomal regions, or sets of
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`chromosomal regions, to determine if aneuploidy exists. (Paper 1, p. 15-16).
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`Sequenom further alleges that a person of ordinary skill in the art would
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`understand that disclosure of chromosomal regions is a disclosure of using
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`windows to analyze the data. Id. The Board adopted Sequenom’s allegations.
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`(Paper 7, p. 10-11). However, a person of ordinary skill in the art would
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`understand that a “chromosomal region” as used in Lo II does not refer to a
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`window of defined length as required by the claims of the Fan ’415 patent. (Ex.
`
`2117, ¶¶ 94 - 97). Rather, a chromosomal region refers to a segment of a
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`chromosome that is not necessarily defined by size, whereas windows as described
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`in the Fan ’415 patent specification are “windows of defined length.”(Ex. 2117, ¶
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`97). For example, the size of a given region in an individual may vary from person
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`to person. Id. Thus, there is no pre-selected knowledge of the size of that region –
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`the length of the region is not a “defined length” based measurement. Id. Nor are
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`chromosomal regions equal in length, as are the properly construed “windows of
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`defined length” claimed in the Fan ’415 patent. (Ex. 2117, ¶¶ 54 – 84, 97).
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`1. Windows in the Fan ’415 Patent Are a Tool USED TO TEST for
`Aneuploidy
`
`
`The Fan ’415 patent specification defines the term “chromosome portion” as
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`“either an entire chromosome or a significant fragment of a chromosome.” (Exhibit
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`1001, 4:5-7). The Fan ’415 patent specification also generally refers to
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`chromosome regions in an analogous manner. (Ex. 2117, ¶¶ 112 - 114). In both
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`cases the terms “chromosome portion” and “chromosome region” mean something
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`different than a window. (Ex. 2117, ¶ 115). That is, a person of ordinary skill in
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`the art would understand that a chromosome portion is being tested for aneuploidy,
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`but a window is used to do that testing. (Ex. 2117, ¶¶ 112 - 116).
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`The distinction between Fan’s “windows of defined length” and Fan’s
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`“chromosome portions” is also made clear by the language of claim 1. (Ex. 2117,
`
`¶ 115). The preamble of claim 1 states that it is directed to “[a] method of testing
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`for an abnormal distribution of a specified chromosome portion.” Then, in the
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`body of the claim, it states in-part “determining values for numbers of sequence
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`tags mapping to chromosome portions by using a number of windows of defined
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`length within normally and abnormally distributed chromosome portions to
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`obtain a first value and a second value therefrom.” (Ex. 1001, claim 1) (emphasis
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`added). A person of ordinary skill in the art would understand that windows are
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`found within chromosome portions, i.e., chromosome regions. (Ex. 2117, ¶¶ 115 -
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`116). A person of ordinary skill would further understand that chromosome
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`portions are not necessarily defined, whereas “windows” are specifically defined
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`by size, location, and content. Id. Accordingly, the Fan ’415 patent specification
`
`makes it clear that windows and chromosome portions (or the Lo equivalent term
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`“chromosomal region”) are not interchangeable terms. Id.
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`2. Chromosomal Regions in Lo II Are BEING TESTED for Aneuploidy
`
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`In contrast, a “chromosomal region” in Lo II is a polynucleotide sequence
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`whose imbalance is itself being tested. (Ex. 2117, ¶¶ 99 - 104). For example, the
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`background section of Lo II states “[f]etal chromosomal aneuploidy results from
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`the presence of abnormal dose(s) of a chromosome or chromosomal region.”
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`(Exhibit 1002, ¶ [0004]. Lo defines the term “chromosomal aneuploidy” to mean
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`“a va