`
`UNITED STATES PATENT AND TRADEMARKOFFICE
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`WWW.USpLO.ZOV
`
`APPLICATION NO.
`
`FILING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONFIRMATIONNO.
`
`90/012,894
`
`06/17/2013
`
`6,440,706 BI
`
`LT00831 REX
`
`8442:
`
`11332
`7590
`.
`Banner & Witcoff, Ltd.
`
`Attorneys forclient 001107 CAMPELL, BRUCER.
`1100 13th Street N.W.
`
`07/03/2013
`
`EXAMIN
`
`Washington, DC 20005-4051
`
`3991
`
`MAIL DATE
`
`07/03/2013
`
`DELIVERY MODE
`
`PAPER
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Page 708 of 1224
`PTOL-90A (Rev. 04/07)
`
`Page 708 of 1224
`
`

`

`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`Commissioner for Patents
`United States Patents and Trademark Office
`.
`P.O.Box 1450
`Alexandria, VA 22313-1450
`www. uspto.gov
`
`THIRD PARTY REQUESTER'S CORRESPONDENCE ADDRESS
`LIFE TECHNOLOGIES CORPORATION
`ATTN: IP DEPARTMENT
`
`5791 VAN ALLEN WAY:
`CARLSBAD, CA 92008
`
`|
`
`~ Date:
`
`_ MAILED
`
`JUL 03 2013 -
`CENTRAL REEXAMINATION UNIT
`
`EX PARTE REEXAMINATION COMMUNICATION TRANSMITTAL FORM
`
`REEXAMINATION CONTROL NO. : 90012894
`
`PATENT NO. : 6440706
`
`ART UNIT : 3991
`
`Enclosed is a copy of the latest communication from the United States Patent and Trademark
`Office in the above identified ex parte reexamination proceeding (37 CFR 1.550(f)).
`
`Wherethis copy is supplied after the reply by requester, 37 CFR 1.535, or the timefor filing a
`reply has passed, no submission on behalf of the ex parte reexamination requester will be
`acknowledged or considered (37 CFR 1.550(g)).
`
`Page 709 of 1224
`
`Page 709 of 1224
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`

`

`ar
`
`Ex Parte Reexamination Interview
`Summary - Pilot Program for Waiverof
`Patent Owner’s Statement
`
`.
`
`Control No.
`
`90/012,894
`
`Patent For Which Reexamination
`R
`ted
`
`.440.706.
`Art Unit
`3901
`
`cc: Requester(if third party requester)
`
`-- The MAILING DATEof this communication appears on the cover sheet with the correspondenceaddress.--
`
`All participants (USPTO official and patent owner):
`
`(1) Karen Ward, CRU
`
`(2) Franklin Wolfe, 19724
`
`Date of Telephonic Interview: June 27, 2013.
`
`The-USPTOofficialrequested waiver of the patent owner’s statement pursuantto the pilot program for waiverof
`patent owner's statement in ex parte reexamination proceedings.*
`
`[-] The patent owner agreed to waiveits right to file a patent owner’s statement under 35 U.S.C. 304 in the event
`reexamination is ordered for the above-identified patent.
`
`[_] The patent owner did not agree to waiveits rightto file a patent owner’s statement under 35 U.S.C. 304 atthis
`time.
`
`The patent owneris not required to file a written statementof this telephone communication under 37 CFR 1.560(b) or
`otherwise. However, any disagreementas to this interview summary must be brought to the immediate attention of
`the USPTO, and no later than one month from the mailing date of this interview summary. Extensions of time are
`governed by 37 CFR 1.550(c).
`
`*For more information regarding this pilot program, see Pilot Program for Waiver of Patent Owner's Statementin Ex
`Parte Reexamination Proceedings, 75 Fed. Reg. 47269 (August 5, 2010), available on the USPTO Website at
`http:/Awww.uspto. gov/patents/law/notices/2010.jsp.
`
`x] USPTO personnel were unable to reach the patent owner.
`
`Thepatent owner may contact the USPTO personnelat the telephone numberprovided belowit the patent owner
`decides to waive the rightto file a Patent owner’s statement under 35 U.S.C. 304.
`
`571-272-7932
`/Karen Ward/
`Signature and telephone number of the USPTO official who contacted or attempted to contact the patent owner.
`
`;
`U.S. Patent and Trademark Office
`PTOL-2292 (08-10) Ex Parte Reexamination Interview Summary - Pilot Program for Waiver of Patent Owner's Statement
`Page 710 of 1224
`:
`
`PaperNo.
`
`Page 710 of 1224
`
`

`

`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`www.uspto.gov
`
`APPLICATION NO.
`
`
`
`
` FILING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`
`
`
`CONFIRMATIONNO.
`
`90/012,894
`
`06/17/2013
`
`6,440,706 B1
`
`LT00831 REX
`
`8442
`
`otf “
`
`Ban
`
`Banner & Witeof, Ltd
`Attorneys for client 001107
`1100 13th Street N.W.
`sie ao
`Washington, DC 20005-4051
`
`[oe
`CAMPELL, BRUCER
`
`3991
`
`MAIL DATE
`
`08/28/2013
`
`PRN
`
`DELIVERY MODE
`
`PAPER
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Page 711 of 1224
`PTOL-90A (Rev. 04/07)
`
`Page 711 of 1224
`
`

`

` UNITED STATES PATENTAND TRADEMARK OFFICE
`
`Corarnissioner for Patents
`United States Patent and Trademark Office
`P.O. Box1450
`Alexandria, VA 22313-1440
`wunUSPTO.gow
`
`DO NOT USEIN PALM PRINTER
`
`(THIRD PARTY REQUESTER'S CORRESPONDENCE ADDRESS)
`
`LIFE TECHNOLOGIES CORPORATION
`
`ATTN: IP DEPARTMENT
`
`5791 VAN ALLEN WAY
`
`CARLSBAD, CA 92008
`
`EX PARTE REEXAMINATION COMMUNICATION TRANSMITTAL FORM
`
`REEXAMINATION CONTROL NO. 90/012,894.
`
`PATENT NO. 6,440,706 _B1 E.
`
`ART UNIT 3997.
`
`Enclosedis a copy of the latest communication from the United States Patent and Trademark
`Office in the above identified ex parte reexamination proceeding (87 CFR 1.550(f)).
`
`Wherethis copy is supplied after the reply by requester, 37 CFR 1.535, or the timeforfiling a
`reply has passed, no submission on behalf of the ex parte reexamination requester will be
`acknowledged or considered (37 CFR 1.550(g)).
`
`PTOL-465 (Rev.07-04)
`Page 712 of 1224
`
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`

`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Page 2
`
`Request for Ex Parte Reexamination
`
`A request for ex parte reexamination of claims 1-12, 14-16, 19-32, 38-44, 46-48
`
`and 51-64 of U.S. Patent 6,440,706 wasfiled on June 17, 2013 by a third party
`
`requester.
`
`Decision on Request
`
`A substantial new question of patentability (SNQ) affecting claims 1-12, 14-16,
`
`19-32, 38-44, 46-48 and 51-64 of U.S. Patent 6,440, 706 is raised by the request for ex
`
`parte reexamination.
`
`Scope of the Claims
`
`In reexamination, patent claims are construed broadly. In re Yamamoto, 740 F.2d
`
`1569, 1571, 222 USPQ 934, 936 (Fed. Cir. 1984) (claims given "their broadest
`
`reasonable interpretation consistent with the specification"). The independent claims
`
`subject to reexamination read as follows:
`
`1. A method for determining the ratio of a selected genetic sequencein a population of
`genetic sequences, comprising the stepsof:
`
`diluting nucleic acid template molecules in a biological sample to form a set
`comprising a plurality of assay samples;
`
`amplifying the template molecules within the assay samples to form a population
`of amplified molecules in the assay samplesofthe set;
`
`analyzing the amplified molecules in the assay samples of the set to determine a
`first number of assay samples which contain the selected genetic sequence and a
`second numberof assay samples which contain a reference genetic sequence;
`
`comparing the first number to the second numberto ascertain a ratio which
`reflects the composition of the biological sample.
`
`38. A method for determining the ratio of a selected genetic sequence in a population of
`genetic sequences, comprising the stepsof:
`
`Page 713 of 1224
`
`Page 713 of 1224
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`

`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Page 3
`
`amplifying template molecules within a set comprising a plurality of assay
`samples to form a population of amplified molecules in each of the assay samples of the
`set;
`
`analyzing the amplified molecules in the assay samples of the set to determine a
`first number of assay samples which contain the selected genetic sequence and a
`second numberof assay samples which contain a reference genetic sequence, wherein
`at least one-fiftieth of the assay samplesin the set comprise a number(N) of molecules
`suchthat 1/N is larger than the ratio of selected genetic sequencesto total genetic
`sequences required to determine the presenceof the selected genetic sequence;
`
`comparing the first number to the second numberto ascertain a ratio which
`reflects the composition of the biological sample.
`
`Claim Interpretation
`
`The biological sample of claim 1 can either be comprised of cells, tissues, bodily
`
`fluids, etc. or cell free, as recited in dependent claims 6 and 24.
`
`In either case, nucleic
`
`acids are distributed throughout the sample. Therefore any processin which the
`
`sample is diluted is considered "diluting nucleic acid template molecules in a biological
`
`sample.” The “ratio of a selected genetic sequence’is interpreted as the ratio of the
`
`selected genetic sequence to the reference genetic sequence.
`
`With regard to the limitation in claim 38 “the assay samplesin the set comprise a
`
`number (N) of molecules such that 1/N is larger than the ratio of selected genetic
`
`sequencesto total genetic sequences required to determine the presence of the
`
`selected genetic sequence,” it is impossible to ascertain a value for N becausethis
`
`numbercan only be determined after the method has been performed. The "plain
`
`English" meaning ofthis limitation is that, for example, if the selected sequenceis
`
`presentin the biological sample at a level of 1 copy in 50, then the assay samples
`
`should contain at least 50 total copies (“selected” + “reference”) of the genetic sequence
`
`to ensure a reasonable likelihood that there is a selected genetic sequence present in
`
`the sample to be amplified and detected. This assumesthat a single copy of a
`
`sequenceis sufficient to be detected after amplification and detection, which may or
`
`may not be true, depending on experimental conditions (how many amplification cycles,
`
`detection method used, etc.).
`
`It appears that this information can only be derived ex
`
`Page 714 of 1224
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`

`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Page 4
`
`postfacto, or at least after preliminary experiments have been performed with similar
`
`biological samples. For purposesofinterpreting the prior art, if a reference showsthat a
`
`selected genetic sequence was detected in an assay sample, then clearly that assay
`
`sample contained enough template nucleic acid molecules to enable detection of the
`
`selected genetic sequence and this claim limitation is met, whether or not “N”is
`
`specifically disclosed.
`
`Documents Submitted by Requester
`
`Li et al., "Amplification and analysis of DNA sequencesin single human
`sperm and diploid cells." Nature 335(6189):414-7 (1988)
`
`Zhang etal., "Whole genome amplification from a single cell: implications
`for genetic analysis." PNAS USA, 89(13):5847-51 (1992)
`
`Jeffreys et a/., "Amplification of human minisatellites by the polymerase
`chain reaction: towards DNAfingerprinting of single cells." Nucl. Acids.
`Res., vol 16, no. 23, pages 10953-10971 (1988)
`
`Kalinina et a/., "Nanoliter scale PCR with TaqMan detection," Nucl. Acids.
`Res. vol 25, 1999-2004 (1997)
`
`Chou et al., "Prevention of pre-PCR mis-priming and primer dimerization
`improves low-copy-number amplifications," Nucleic Acids Res., 20(7):
`1717-1723 (April 11, 1992)
`
`Burg, et al., "Direct and sensitive detection of a pathogenic protozoan,
`Toxoplasma gondii, by polymerase chain reaction." J. Clin. Microbiol. 27,
`1787-1792 (1989)
`
`Trumperet al., "Single-Cell Analysis of Hodgkin and Reed-Sternberg Cells:
`Molecular Heterogeneity of Gene Expression and p53 Mutations," Blood, 87 :
`3097-3115 (1993)
`
`Kanzler et a/., "Molecular Single Cell Analysis Demonstrates the Derivation
`of Peripheral Blood-Derived Cell Line (L 1236) From the Hodgkin/Reed-
`Sternberg Cells of a Hodgkin's Lymphoma Patient,” Blood, 87:3429-3436
`(1996)
`
`Gravel et al., "Single-cell analysis of the t(14; 18)(q32;q21) chromosomal
`translocation in Hodgkin's disease demonstrates the absenceofthis
`
`Page 715 of 1224
`
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`

`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Page 5
`
`translocation in neoplastic Hodgkin and Reed-Sternberg cells," Blood
`91(8):2866-74 (Apr 15, 1998)
`
`Marcucci et al., "Detection of Unique ALLA.(MLL) Fusion Transcripts in
`Normal Human Bone Marrow and Blood: Distinct Origin of Normal versus
`Leukemic ALL 1 Fusion Transcripts," Cancer Res, 58:790-793. (February 15,
`1998)
`
`Flint et al., "NR2A Subunit Expression Shortens NMDA Receptor Synaptic
`Currents in Developing Neocortex," J. Neurosci., 17(7):2469-2476 (April 1,
`1997)
`
`Ponten et al., "Genomic analysis of single cells from human basalcell cancer
`using laser-assisted capture microscopy," Mutation Research Genomics 382,
`45-55 (1997)
`
`Review of the ‘706 patentfile shows that Li and Zhang werecited in an information
`
`disclosure statement but not applied in any rejection. None of the other references
`
`were considered during prosecution.
`
`Requester’s Proposed SNQs
`
`Requester proposes 24 SNQs (summarized in Request, pp. 1-2).
`
`1. Requester considers claims 1-3, 7-11, 14-16, 19, 21, 22, 27 and 32
`
`unpatentable over Li (proposed SNQs1 and4).
`
`Li discloses a method in which a ratio of genetic sequences (B-globin) was
`
`obtained from a tissue culture flask containing co-cultured cells (the biological sample)
`of an individual homozygousfor the B° allele (“selected genetic sequence,” which
`causessickle cell anemia) and anotherindividual homozygousforthe B” allele (normal,
`
`“reference genetic sequence”). The nucleic acid template molecules, contained within
`
`the cultured cells, were diluted by isolating single cells from the culture. Thirty seven
`
`single cells (assay samples) were lysed, and the released DNA was subjected to
`
`polymerase chain reaction (PCR) to amplify the portion of the globin gene containing
`
`Page 716 of 1224
`
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`

`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Page 6
`
`the sickle cell mutation. Amplified DNA was hybridized with allele specific probes.
`
`It
`
`wasfound that 19 of the samples contained the normal allele, 12 contained the sickle
`
`cell allele, and 6 samples did not hybridize with either probe. These numerical values
`
`were “compared,” which inherently ascertains a ratio between the two values (19:12).
`
`See pp. 414-415, Fig. 1.
`
`In another experiment (p. 415, Fig. 2), the biological sample was semen obtained
`
`from a subject heterozygous for a polymorphism in the LDLr gene. Eighty individual
`
`sperm cells were lysed and the DNA subjected to PCR followed by hybridization with
`
`allele specific probes. A total of 55% of sperm cells (“assay samples”) gave a
`
`hybridization signal.
`
`It was found that 22 assay samples contained one allele and 21
`
`samples contained the other, a ratio of 22:21. Either allele can be considered the
`
`“selected genetic sequence”or the “reference genetic sequence.”
`
`A reasonable examiner would considerthe disclosure of Li important in
`
`determining whether claims 1-3, 7-11, 14-16, 19, 21, 22, 27 and 32 are patentable.
`
`Accordingly, Li raises a SNQ regarding claims 1-3, 7-11, 14-16, 19, 21, 22, 27 and 32.
`
`2. Requester considers claims 38, 39, 46 and 51 unpatentable over Zhang
`
`(proposed SNQ 14).
`
`Zhang discloses a method similar to that of Li.
`
`In Zhang’s method (p. 5847), a
`
`biological sample (semen) wasdiluted into 18 assay samples by selecting and isolating
`
`18 single sperm cells. Each cell was lysed and the released DNA waspre-amplified by
`
`repeated primer extension reactions with a set of random 15-merprimers (primer-
`
`extension preamplification, or PEP). The PEP process was estimated to produceat
`
`least 30 copies of every sequence capable of amplification (p. 5848, col. 1). After PEP,
`
`aliquots of each sample were subjected to a two-step hemi-nested PCR processto
`
`determine the genotypeat each of 12 different loci. PCR wasfirst performed using a
`
`first pair of primers designed to amplify the genetic sequenceof interest, then an aliquot
`
`of the sample was removed and subjected to a second PCR using one primerfrom the
`
`Page 717 of 1224
`
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`

`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Page 7
`
`first pair and a second primerinternal to the previously amplified sequenceofinterest.
`
`The second set of primers were chosenso that the two possible alleles would produce
`
`amplified fragments of different lengths. This method ensuresspecificity of the PCR
`
`and allows discrimination between the two reaction products (hence, alleles present in
`
`the template molecules) by gel electrophoresis of the final PCR product to determine
`
`fragmentlength (p. 5847, col. 2). Each of the 12 loci were successfully amplified in at
`
`least 15 of the 18 sperm cells (assay samples; see Table 2). The genotype of each cell
`
`wasdeterminedfor twoloci (results for 9 cells shown in Fig. 3). Each of the two APOC2
`
`alleles was foundin 9 cells, the expected 1:1 ratio for this heterozygous sperm donor.
`
`Similarly, analysis of the sex linked STS gene/pseudogene showedthat9 cells carried
`an X chromosomeand 8 carried a Y chromosome(the 18" cell did not yield detectable
`
`STS sequence).
`
`Independent assortment of these two loci was also observed (p. 5848,
`
`col. 2).
`
`A reasonable examiner would consider the disclosure of Zhang importantin
`
`determining whether claims 38, 39, 46 and 51 are patentable. Accordingly, Zhang
`
`raises a SNQ regarding claims 38, 39, 46 and 51.
`
`3. Requester considers claims 4-6, 12, 20, 23-26, and 28-31 unpatentable over
`
`Li in combination with one or more of Zhang, Jeffreys, Kalinina, Chou, Burg,
`
`Trumper, Kanzler, Gravel, Marcucci, Flint and Pontén (proposed SNQs2, 3 and 5-
`
`13).
`
`Li and Zhang are discussed above.
`
`Jeffreys discloses methodsfor amplification of human minisatellite DNA for the
`
`purposeof producing DNAfingerprints of individuals.
`
`In one method, a biological
`
`sample is split into multiple assay samples by isolating single cells, then analyzed in
`
`much the same wayas in Li and Zhang (pp. 10955-10956).
`
`In an alternative method,
`
`isolated (cell free) DNA wasdiluted into multiple assay samples, each containing 6 pg
`
`DNA. This amount was estimated to be equivalent to the amount of DNAin a single
`
`Page 718 of 1224
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`

`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Page 8
`
`cell.
`
`It was concluded that single DNA molecules could befaithfully amplified (pp.
`
`10960-10962).
`
`In the experiment shownin Fig. 4, each assay sample was subjected to
`
`PCR with 4 sets of primers (in a single reaction), the primers designed to amplify two
`
`alleles for each of 2 minisatellites. Successful amplification was obtained, with a mean
`
`failure rate of 638%perallele per reaction, equating to an estimated 0.46 successful
`
`amplification events per 6 pg sample (becausestatistically one would not expect the
`
`template sequence to be present in every sample; p. 10961).
`
`Kalinina discloses a method for PCR amplification and detection using TaqMan
`
`probes. Samplesdiluted to contain approximately 1 template molecule are subjected to
`
`TaqMan PCR in sealed capillary tubes containing a few nanoliters of reactants, then
`
`presence of PCR productis determined by measuring the probe fluorescence (entire
`
`document, see especially p. 2000). The method is considered especially useful for
`
`assays meantto determine the presence or absence of PCR product(i.e. not
`
`quantitative analysis; p. 2004, last paragraph).
`
`Chou discloses a method for “hot start? PCR. The method uses a wax barrier to
`
`separate one or more PCR componentsfrom the remainderof the reactants until heatis
`
`applied to melt the wax (entire document). This method reduces amplification due to
`
`mispriming and primer oligomerization, and is said to be especially useful for PCR with
`
`a sample containing a low numberof template molecules (p. 1722, col. 1).
`
`Burg discloses a method for PCR detection of a single cell of Toxoplasma
`
`gondii. Cells are lysed and PCR is performed for 60 cycles (p. 1790, col. 1; Fig. 4).
`
`Trumperisolated single cells from lymph nodes of patients diagnosed with
`
`Hodgkin's disease. Cells were lysed, cDNA was producedbyreversetranscription and
`
`PCR performed on the cDNA (see methods, pp. 3098-3100). One cell was found to
`
`have a mutation in exon 7 of the p53 gene, at a known "hot spot."
`
`Page 719 of 1224
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`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Page 9
`
`Kanzler isolated single cells from bone marrow of patients diagnosed with
`
`Hodgkin's disease (p. 3429). PCR analysis identified three gene rearrangements
`
`(abstract). Kanzler suggests, “Using tumor clone-specific primers ... residual tumor
`
`cells may be detected after therapy” (p. 3434, col. 2).
`
`Gravel used single cell PCR analysis to determine the presence or absence of a
`
`chromosomaltranslocation, t(14;18)(q32;q21), in cells from bone of patients diagnosed
`
`with Hodgkin’s disease (see methods, pp. 2866-2868).
`
`Marcucci discloses a chromosome segment which is subject to partial tandem
`
`duplication, which is a common defect found in acute myeloid leukemia.
`
`Flint used single cell reverse transcription and PCR to study gene expression in
`
`developing neocortex tissues (abstract).
`
`Pontén performed single cell PCR on cells derived from a single tumor and
`
`showedthat the tumor contained multiple p53 mutations. Some cells contained more
`
`than one mutation of the p53 gene (see overview on p. 52).
`
`A reasonable examiner would consider the disclosure of Li, in combination with
`
`one or more of Zhang, Jeffreys, Kalinina, Chou, Burg, Trumper, Kanzler, Gravel,
`
`Marcucci, Flint and Pontén, important in determining whetherclaims 4-6, 12, 20, 23-26,
`
`and 28-31 are patentable. Accordingly, Li in combination with one or more of Zhang,
`
`Jeffreys, Kalinina, Chou, Burg, Trumper, Kanzler, Gravel, Marcucci, Flint and Pontén
`
`raises a SNQ regarding claims 4-6, 12, 20, 23-26, and 28-31.
`
`4. Requester considers claims 40-44, 47, 48 and 52-64 unpatentable over
`
`Zhang in combination with one or more of Li, Kalinina, Chou, Burg, Trumper,
`
`Kanzler, Gravel, Marcucci, Flint and Pontén (proposed SNQs 15-24).
`
`Page 720 of 1224
`
`Page 720 of 1224
`
`

`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Each referenceis discussed above.
`
`Page 10
`
`A reasonable examiner would consider the disclosure of Zhang in combination
`
`with Li, Kalinina, Chou, Burg, Trumper, Kanzler, Gravel, Marcucci, Flint and Pontén
`
`important in determining whether claims 40-44, 47, 48 and 52-64 are patentable.
`
`Accordingly, Zhang in combination with Li, Kalinina, Chou, Burg, Trumper, Kanzler,
`
`Gravel, Marcucci, Flint and Pontén raises a SNQ regarding claims 40-44, 47, 48 and
`
`52-64.
`
`Conclusion
`
`In view of the analysis above, the requestfor reexamination is GRANTED.
`
`Claims 1-12, 14-16, 19-32, 38-44, 46-48 and 51-64 of US Patent 6,440,706 will be
`
`reexamined.
`
`Duty to Disclose
`
`The patent owneris reminded of the continuing responsibility under 37 CFR
`
`1.565(a) to apprise the Office of anylitigation activity, or other prior or concurrent
`
`proceeding, involving Patent No. 6,440,706 throughout the course of this reexamination
`
`proceeding. The third party requesteris also remindedof the ability to similarly apprise
`
`the Office of any suchactivity or proceeding throughoutthe course of this reexamination
`
`proceeding. See MPEP §§ 2207, 2282 and 2286.
`
`Waiver of Right to File Patent Owner Statement
`
`In areexamination proceeding, Patent Owner may waivethe right under 37
`
`C.F.R. 1.530 to file a Patent Owner Statement. The waiver document must contain a
`
`statement that Patent Ownerwaivesthe right under 37 C.F.R. 1.530 to file a Patent
`
`OwnerStatementand proof of service in the mannerprovided by 37 C.F.R. 1.248, if the
`
`request for reexamination was madebya third party requester (see 37 C.F.R 1.550(f)).
`
`Page 721 of 1224
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`Page 721 of 1224
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`

`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Page 11
`
`Amendment in Reexamination Proceedings
`
`Patent owneris notified that any proposed amendmentto the specification and/or
`
`claimsin this reexamination proceeding must comply with 37 CFR 1.530(d)-(j), must be
`
`formally presented pursuant to 37 CFR 1.52(a) and (b), and must contain any fees
`
`required by 37 CFR 1.20(c).
`
`Service of Papers
`
`After thefiling of a request for reexamination by a third party requester, any
`
`documentfiled by either the patent ownerorthe third party requester must be served on
`
`the other party (or parties where two or morethird party requester proceedings are
`
`merged) in the reexamination proceeding in the manner provided in 37 CFR 1.248. See
`
`37 CFR 1.550/(f).
`
`Correspondence
`
`Anyinquiry concerning this communication or earlier communications from the
`
`examiner should be directed to BRUCE CAMPELL whosetelephone numberis 571-
`
`272-0974. The examiner can normally be reached on Monday- Thursday from 8:00 to
`
`5:00. The examiner can also be reached on alternate Fridays.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
`
`supervisor, Deborah Jones, can be reached on 571-272-1535. The fax phone number
`
`for the organization wherethis application or proceeding is assigned is 571-273-9900.
`
`Information regarding the status of an application may be obtained from the
`
`Patent Application Information Retrieval (PAIR) system. Status information for
`
`published applications may be obtained from either Private PAIR or Public PAIR.
`
`Status information for unpublished applications is available through Private PAIR only.
`
`For more information about the PAIR system, see http://pair-direct.uspto.gov. Should
`
`you have questions on accessto the Private PAIR system, contact the Electronic
`
`Business Center (EBC) at 866-217-9197(toll-free).
`
`Page 722 of 1224
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`Page 722 of 1224
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`

`

`Application/Control Number: 90/012,894
`Art Unit: 3991
`
`Page 12
`
`All correspondencerelating to this ex parte reexamination proceeding should be
`directed:
`By EFS:
`
`Registered users may submit via the electronic filing system EFS-Webat
`
`htips://efs.uspto.gov/efile/myportal/efs-registered
`
`By Mail to:
`
`Mail Stop Ex Parte Reexam
`Central Reexamination Unit
`Commissioner for Patents
`United States Patent & Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`By FAX to:
`
`(571) 273-9900
`Central Reexamination Unit
`
`By hand:
`
`Customer Service Window
`Randolph Building
`401 Dulany Street
`Alexandria, VA 22314
`
`/Bruce Campell/
`Patent Reexamination Specialist
`Central Reexamination Unit 3991
`
`Conferee:
`
`/Padmashri Ponnaluri/
`Patent Reexamination Specialist
`CRU-3991
`
`/Deborah D Jones/
`Supervisory Patent Examiner, Art Unit 3991
`
`Page 723 of 1224
`
`Page 723 of 1224
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`

`

`Order Granting / Denying Request For
`.
`:
`Ex Parte Reexamination
`
`Control No.
`
`90/012,894
`
`Examiner
`
`BRUCE CAMPELL
`
`Patent Under Reexamination
`
`6,440,706 BIE
`
`Art Unit
`
`3991
`
`--The MAILING DATEof this communication appears on the cover sheet with the correspondence address--
`
`The request for ex parte reexamination filed 17 June 2013 has been considered and a determination has
`been made. Anidentification of the claims, the references relied upon, and the rationale supporting the
`determination are attached.
`
`Attachments: a)L_] PTO-892,
`
`b)X] PTO/SB/08,
`
`c)L_] Other:
`
`1. The request for ex parte reexamination is GRANTED.
`
`RESPONSE TIMES ARE SET AS FOLLOWS:
`
`For Patent Owner's Statement (Optional): TWO MONTHS from the mailing date of this communication
`(37 CFR 1.530 (b)). EXTENSIONS OF TIME ARE GOVERNED BY 37 CFR 1.550(c).
`
`For Requester's Reply (optional): TWO MONTHS from the date of service of any timelyfiled
`Patent Owner's Statement (37 CFR 1.535). NO EXTENSION OF THIS TIME PERIOD IS PERMITTED.
`lf Patent Owner does notfile a timely statement under 37 CFR 1.530(b), then no reply by requester
`is permitted.
`
`2.[_] The request for ex parte reexamination is DENIED.
`
`This decision is not appealable (35 U.S.C. 303(c)). Requester may seek review by petition to the
`Commissioner under 37 CFR 1.181 within ONE MONTH from the mailing date of this communication (37
`CFR 1.515(c)). EXTENSION OF TIME TO FILE SUCH A PETITION UNDER 37 CFR 1.181 ARE
`AVAILABLE ONLYBY PETITION TO SUSPEND OR WAIVE THE REGULATIONS UNDER
`37 CFR 1.183.
`
`In due course, a refund under 37 CFR 1.26 (c ) will be made to requester:
`
`a) L] by Treasury checkor,
`
`b) L] by credit to Deposit Account No.
`
`, or
`
`c) L] by credit to a credit card account, unless otherwise notified (35 U.S.C. 303(c)).
`
` cc:Requester (
`
`/Bruce Campell/
`Patent Reexamination Specialist
`Central Reexamination Unit 3991
`
`if third party
`U.S. Patent and Trademark Office
`
`requester
`
`PTOL-471 (Rev. 08-06)
`
`Office Action in Ex Parte Reexamination
`
`Part of Paper No. 20130725
`
`Page 724 of 1224
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`Page 724 of 1224
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`

`

`EXHIBIT 2
`
`Page 725 of 1224
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`

`

`Doc code: IDS
`Doc description: Information Disclosure Statement (IDS) Field
`
`PTO/SB/08a (01-10)
`Approvedfor use through 07/31/2012. OMB 0651-0031
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unlessit contains a valid OMB control number.
`
`
`
`Application Number
`Unknown
`INFORMATION DISCLOSURE
`Filing Date
`June 17, 2013
`
`STATEMENT BY APPLICANT
`-
`;
`
`
`(Not for submission under 37 CFR 1.99) First Named Inventor|Bert Vogelstein
`Art Unit
`Unknown
`
`
`
`Examiner Name
`
`Unknown
`
`
`
`
`
`
`Sheet
`4
`of
`2
`Docket Number
`LT00831 REX
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`CHOU, QUIN et al., "Prevention of pre-PCR mis-priming and primer dimerization improves
`
`IBC
`low-copy-number amplifications", Nucleic Acids Research, Vol. 20, No. 7, Oxford University
`
`Press, 1992, 1717-1723
`FLINT, ALEXANDER C. etal., "NR2A Subunit Expression Shortens NMDA Receptor Synaptic
`
`Currents in Developing Neocortex", The Journal of Neuroscience, Vol. 17, No. 7, 1997, 2469-
`B.C.
`
`ue
`2476
`GRAVEL, SYLVIA etal., "Single-Cell Analysis of the t(14;18)(q32;q21) Chromosomal
`Translocation in Hodgkin's Disease Demonstrates the Absence of This Translocation in
`
`IB.C/
`Neoplastic Hodgkin and Reed-Sternberg Cells", Blood, Vol. 91, No. 8. 1998, 2866-2874
`JEFFREYS, ALEC et al., "Amplification of human minisatellites by the polymerase chain
`
`BOS
`reaction. towards DNAfingerprinting of single cells", Nucl. Acids Res., Vol. 16, No. 23, 1988,
`10953-10971
`nr |
`C6
`KALININA, OLGA et al., "Nanoliter Scale PCR with TaqMan Detection", Nucleic Acids
`
`/8.G./ Research, Vol. 25, No. 10, 1997, 1999-2004
`cT
`KANZLER, H et al., "Molecular single cell analysis demonstrates the derivation of a peripheral
`blood-derived cell line (L1236) from the Hodgkin/Reed-Sternberg cells of a Hodgkin's
`IB.
`lymphoma patient", Blood, Vol. 87, No. 8, 1996, 3429-3436
`MARCUCCI, GUIDO et al., "Detection of Unique ALL1 (MLL) Fusion Transcripts in Normal
`Human Bone Marrow and Blood:Distinct Origin of Normal versus Leukemic ALL1 Fusion
`Transcripts", Cancer Research, Vol. 58, 1998, 700-793
`cg
`PONTEN, FREDRIK et al., "Genomic analysis of single cells from human basal cell cancer
`using laser-assisted capture microscopy", Mutation Research Genomics, Vol. 382, No. 1-2,
`im]
`
`B.C 1997, 45-55
`
`
`
`
`U.S.PATENTS
`Examiner
`Cite
`Patent
`Kind
`Issue Date
`Nameof Patentee or Applicant of
`Pages, Columns,Lines, Where
`Initial*
`No
`Number
`Code!
`cited Document
`Relevant Passages or Relevant Figures
`Appear
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`U.S.PATENT APPLICATION PUBLICATIONS
`Examiner
`Cite
`Publication
`Kind
`Publication Date
`Nameof Patentee or Applicant of
`Pages, Columns, Lines, Where
`Initial*
`No
`Number
`Code’
`cited Document
`Relevant Passages or Relevant
`Figures Appear
`
`
`
`
`
`
`
`
`FOREIGN PATENT DOCUMENTS
`
`
`
`Country
`Code”
`
`Kind
`Code"
`
`
`
`
`
`Publication
`Date
`
`T
`
`
`
`Pages,Columns,Lines where
`Nameof Patentee or
`Foreign
`Relevant Passages or Relevant
`Applicant of cited
`Document
`Number
`Document
`Figures Appear
`
`
`NON-PATENT LITERATURE DOCUMENTS
`Examiner
`Cite
`Include nameof the author (in CAPITAL LETTERS),title of the article (when appropriate),title of the item (book,
`T
`Initial*
`No
`magazine, journal, serial, symposium, catalog, etc.), date, page(s), volume-issue number(s), publisher, city and/or country
`
`where published.
`mA
`ci
`BURG, J. L. etal., "Direct and Sensitive Detection of a Pathogenic Protozoan, Toxoplasma
`Al
`gondii, by Polymerase Chain Reaction", Journal of Clinical Microbiology, Vol. 27, No. 8, 1989,
`
`1787-1792
`
`Examiner
`Initial*
`
`Cite
`No
`
`c2
`
`c3
`
`c4
`
`c5
`
`cs
`
`BC/
`1d td
`
`Page 726 of 1224
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`Page 726 of 1224
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`

`

`Doc code: IDS
`Doc description: Information Disclosure Statement (IDS) Field
`
`PTO/SB/08a (01-10)
`Approvedfor use through 07/31/2012. OMB 0651-0031
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unlessit contains a valid OMB control number.
`
`
`
`Application Number
`Unknown
`INFORMATION DISCLOSURE
`Filing Date
`June 17, 2013
`
`STATEMENT BY APPLICANT
`-
`;
`
`
`(Not for sub