`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMIVHSSIONER FOR PATENTS
`PO. Box 1450
`Alexandria1 Virginia 22313-1450
`wwwusptogov
`
`
`
`
`
`14/374,181
`
`07/23/2014
`
`Takaomi Fukuhara
`
`061352—0530
`
`3739
`
`53080
`7590
`0971072015
`McDermon Will and Emery LLP —
`The McDermott Building
`WEIDNER’ ADAM M
`500 North Capitol Street, NW.
`WASHINGTON, DC 20001
`
`PAPER NUMBER
`
`1649
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`09/10/2015
`
`ELECTRONIC
`
`Please find below and/0r attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above—indicated "Notification Date" to the
`following e—mail address(es):
`
`mweipdocket @ mwe.com
`
`PTOL—90A (Rev. 04/07)
`
`

`

`
`
`Applicant(s)
`Application No.
` 14/374,181 FUKUHARA ET AL.
`
`
`AIA (First Inventorto File)
`Art Unit
`Examiner
`Office Action Summary
`
`
`ADAM M. WEIDNER first“ 1649
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE g MONTHS FROM THE MAILING DATE OF
`THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR1. 136(a).
`after SIX () MONTHS from the mailing date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`
`In no event, however, may a reply be timely filed
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`-
`-
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`Status
`
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`1)IXI Responsive to communication(s) filed on 5/28/15.
`[I A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
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`2b)|:| This action is non-final.
`a)IXl This action is FINAL.
`3)I:I An election was made by the applicant in response to a restriction requirement set forth during the interview on
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`; the restriction requirement and election have been incorporated into this action.
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`4)|:I Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under EX parte Quay/e, 1935 CD. 11, 453 O.G. 213.
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`Disposition of Claims*
`
`5)I:I Claim(s) 3 4 7-10 12 and 14 is/are pending in the application.
`5a) Of the above claim(s)
`is/are withdrawn from consideration.
`6)|:l Claim(s) _ is/are allowed.
`
`7)IZ| Claim(s) 34 7- 10 12 and 14 is/are rejected.
`8)I:I Claim(s)_ is/are objected to.
`
`9)|:l Claim(s
`are subject to restriction and/or election requirement.
`(I
`* If any claims have been determined allowable, you may be eligible to benefit from the Patent Prosecution Highway program at a
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`participating intellectual property office for the corresponding application. For more information, please see
`htt
`://\WIAN.usoto. ov/ atents/init events) .h/index.
`
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`‘3 , or send an inquiry to PF"I-Ifeedback{<‘buspto.qov.
`
`
`
`Application Papers
`
`10)I:I The specification is objected to by the Examiner.
`11)|:I The drawing(s) filed on _ is/are: a)I:I accepted or b)I:I objected to by the Examiner.
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`
`Priority under 35 U.S.C. § 119
`12)I:I Acknowledgment is made of a claim for foreign priority under 35 U.S.C. §119(a)-(d) or (f).
`Certified copies:
`
`b)I:I Some” c)I:I None of the:
`a)I:I All
`1.I:I Certified copies of the priority documents have been received.
`2.I:I Certified copies of the priority documents have been received in Application No.
`3.|:I Copies of the certified copies of the priority documents have been received in this National Stage
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`application from the International Bureau (PCT Rule 17.2(a)).
`** See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`
`
`
`3) D Interview Summary (PT0_413)
`1) E Notice of References Cited (PTO-892)
`Paper No(s)/Mai| Date.
`.
`.
`—
`4) I:I Other'
`2) D InformatIon DIscIosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`Paper No(s)/Mai| Date
`US. Patent and Trademark Office
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20150827
`
`

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`Application/Control Number: 14/374,181
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`Art Unit: 1649
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`Page 2
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`The present application is being examined under the pre-AIA first to invent provisions.
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`In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and
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`103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for
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`the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale
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`supporting the rejection, would be the same under either status.
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`DETAILED ACTION
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`This action is in response to preliminary claim amendments filed 5/28/15. Claims 3-4, 7-10, 12,
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`and 14 are pending and under examination.
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`Withdrawn Rejections
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`The objections to the claims are withdrawn as they either have been corrected by amendment or
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`rendered moot by cancellation of the claim(s).
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`The claims have been amended to remove the phrase “means for”. This creates the rebuttable
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`presumption that the claim elements are not to be treated in accordance with §112, sixth paragraph.
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`The rejection under §112, second paragraph is withdrawn. The claims have been amended to
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`clearly define the pretreatment step as well as removing the “means for” language.
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`The rejections under §102 over either Matson or Luminex are withdrawn. The system claims have
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`removed all “means for” language and are no longer directed to a physical system, but rather to a method
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`of diagnosis.
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`The remaining prior art rejections under §§102 and 103 are withdrawn in light of the amendments
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`and arguments. Both independent claims have been amended to include the limitation of calculating:
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`-
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`-
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`A square root of a sum of square of a value of the tau protein, and
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`A square of the value of AB
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`While such calculations were known in the art, Applicant persuasively argues that there is no
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`motivation in the cited references to select these methods of calculation over any number of alternate
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`known calculations. For example, Caroli (of record) teaches using sum of squares to analyze tau and AB.
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`Caroli does not, however, teach or suggest using the square root of the sum of squares to analyze tau or
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`

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`Application/Control Number: 14/374,181
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`Art Unit: 1649
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`Page 3
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`only the square of AB values. Further, there is no art of record which would render obvious these two
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`specific calculations or for using one to analyze tau and the other to analyze AB.
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`New Rejections Necessitated by Amendment
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`Claim Rejections - 35 USC § 101
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`35 U.S.C.101 reads as follows:
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`Whoever invents or discovers any new and useful process, machine, manufacture, or
`composition of matter, or any new and useful improvement thereof, may obtain a patent
`therefor, subject to the conditions and requirements of this title.
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`Claims 3-4, 7-10, 12, and 14 are rejected under 35 U.S.C. § 101 because the claims as a whole
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`are not directed to patent eligible subject matter. Note that claim 12 has been amended from a system
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`comprising various means for implementing a method (Le, a composition claim) to a system comprising
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`active steps (a method itself). Based upon an analysis with respect to the claim as a whole, these claims
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`do not recite something significantly different than a judicial exception. The rationale for this determination
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`is explained below:
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`New guidance with respect to patent eligibility under 35 U.S.C. § 101 has been provided, effective
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`16 December 2014 and published in the Federal Register V 79 No 241 (please visit
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`http://www.uspto.gov/patents/law/exam/interim_guidance_subject_matter_eligibility.jsp for the published
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`guidance). This guidance has been provided in light of recent court decisions such as Association for
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`Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. _, 133 S. Ct. 2107, 2116, 106, USPQ2d 1972
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`(2013), Mayo Collaborative Serivices v. Prometheus Laboratories, Inc., 566 U.S. _, 132 S. Ct. 1289, 101
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`USPQ2d 1961 (2012), and Alice Corporation PTY. LTD v CLS Bank International.
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`The first step under this guidance is determining if the claim is directed to one of the four statutory
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`categories (process, machine, manufacture, or composition of matter). In this case, the claims are
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`directed to a method (a process). The second step is determining if the claims recite or involve judicial
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`exception(s), such as laws of nature, natural phenomena, natural products, or an abstract idea. In this
`a!
`u
`case, the claims are drawn to observing a natural phenomenon (“detect tau , compare values”, "display
`a!
`it
`results , calculate”; natural phenomenon and abstract ideas) while claims 12 and 14 are drawn to a
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`Application/Control Number: 14/374,181
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`Art Unit: 1649
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`Page 4
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`generic system (as amended this is a method of diagnosing Alzheimer’s; natural correlation) and abstract
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`ideas (e.g., calculating) .
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`Thus, it must be determined if the claim as a whole recites something significantly different than
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`the judicial exceptions.
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`Claim 9 is drawn to a method of diagnosing Alzheimer's disease (AD) by pretreating an intranasal
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`sample with an extraction liquid, detecting tau and AB, calculating a square root of a sum of squares of
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`the tau value and a square of a value of the AB value, comparing only the tau value (“the square root
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`calculated”) with some predetermined value, and displaying the results. Thus, claim 9 amounts to no
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`more than observing the levels of AB and tau in an intranasal specimen. The detection step covers every
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`possible process for detecting both proteins. The comparing step covers any possible comparison to any
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`possible predetermined value. The displaying step may use any possible means of displaying the
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`comparison. The claim itself amounts to no more than an attempt to foreclose others from detecting tau or
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`A8 in intranasal specimens for any reason, as the comparing and displaying steps must be used by
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`others to generate any meaning from the collected data. No specific machine is required and no
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`transformation of the data is achieved. The method simply informs a relevant audience about the natural
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`relationship (i.e., the calculated value is a description of the natural correlation between these biomarkers
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`and AD), the relationship being a natural consequence of how the body expresses tau and the natural,
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`unaltered relationship between tau and a tauopathy. There is nothing in the claim that requires the
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`gathered data (detecting tau protein and AB in an intranasal sample) to be applied in any meaningful way
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`and it would effectively monopolize the judicial exception itself.
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`In other words, the claim as amended is directed to a required data gathering step (detecting tau
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`and AB), indicates a particular sample in which to detect these proteins (which was a routine and
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`conventional choice), describes the natural correlation (the calculating step) and adds abstract steps at a
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`high level of generality (i.e., instructions to "apply it").
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`Claims 3-4 and 7-8 include limitations to the pretreatment step. However, the elements in these
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`claims are no more than what was routine and conventional in the art (using swabs and metering tools to
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`collect intranasal specimens, using formic acid to detect AB, etc). Claim 3 introduces the new limitation of
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`Application/Control Number: 14/374,181
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`Art Unit: 1649
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`Page 5
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`removing proteins greater than 100 kDa. However, the claims remain directed to observing natural
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`intranasal AB and/or tau levels using well-established techniques and performing steps required to utilize
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`the natural correlation. See for example Cizas, cited on form 892, which describes passing AB samples
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`through a 100 kDa-cutoff filter, specifically to analyze the toxicity (and by extension the relevance to
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`Alzheimer's) of AB peptides smaller than this (abstract; introduction; section 2.3). This is similar to the fact
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`pattern in Mayo where the concluding step—that the gathered data “indicated” a certain need—did not in
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`fact require any treatment modification was performed, only that the data indicated the need. The data
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`indicate this need regardless of recognition by another, in the same way displaying a comparison result
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`does not require any actual diagnosis is made. Such is the case with the instant claims that data is
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`gathered and compared, which is used in some way in a "method of diagnosing Alzheimer’s disease”.
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`Using standard collection tools represent routine and conventional methods of gathering the necessary
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`data, while removing proteins greater than 100 kDa serves only to further describe the natural correlation,
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`i.e., it is these proteins which correlate to the disease. All such pre-solution steps were both known in the
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`art and are required to utilize the recited correlation, without significantly more added to the claim once
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`the data is gathered and analyzed.
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`Claim 10 as amended includes extracting in ultrapure water, and extracting AB in a liquid which
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`decomposes AB (e.g., formic acid). These steps were all routine and conventional in the art and none of
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`these steps add significantly more than observing the phenomenon itself. The newly added limitation that
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`the extraction liquid "decomposes AB" (i.e., dissociates aggregates) remains not only a well-known,
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`conventional step (this is the purpose of formic acid extraction) but it is also tied to the natural correlation
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`as described above and previously. Such steps are "insignificant extrasolution activity" to the judicial
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`exception; in other words, collecting the data is required to utilize the natural correlation regarding the
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`relationship between tau/AB and AD as recited by the claims (the calculating step).
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`Claims 12 and 14 are drawn to a system (method) for diagnosing AD in a similar manner as claim
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`9. The differences between amended claim 12 and amended claim 9 are that claim 12 does not require
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`any pretreatment step (and is therefore more generic than claim 9) while requiring the "detecting" step is
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`performed using an immunoassay. However, the requirement that tau and A8 are detected by an
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`Application/Control Number: 14/374,181
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`Art Unit: 1649
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`Page 6
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`immunoassay does not serve to add significantly more to the method as immunoassays are the most
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`popular and ubiquitous method of detecting tau and AB levels; ELISA, Western blot, and immunostaining
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`are all well-known, routine, and conventional methods for detecting these proteins. Claim 12 is therefore
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`ineligible for the same reasons as claim 9: the claim instructs a user to collect the necessary data by
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`routine, conventional methods (detect), informs the user of the natural correlation (calculate), and
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`instructs the user to “apply it” at a high level of generality (compare and display). New claim 14 adds the
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`mental step of determining if the calculated square root (tau value) falls within "a predetermined range of
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`values for Alzheimer's disease". This only adds further, generic instructions to "apply“ the correlation, and
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`such a comparison step is required to utilize the gathered data and calculations.
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`Response to Arguments
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`Applicant's arguments filed 5/28/15 have been fully considered but they are not persuasive.
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`Applicant argues the claims do significantly more than observing and detecting levels of tau and
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`AB. Applicant argues conventional methods of diagnosing AD "typically involved highly-invasive
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`techniques" whereas the instant claims reduce invasiveness (remarks p.9). Applicant further argues that
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`AB is low in an intranasal specimen and tau protein “has not been readily detected in an intranasal
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`specimen” (remarks p.10). This position has been fully considered but is not persuasive. The art of record
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`demonstrates that both AB and tau were known at the time of filing to be detectable in intranasal
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`specimens. For example, Nanjoh (WO 2011/092796; FOR citation 3 on IDS submitted 9/11/14) was
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`discussed in the previous action. To reiterate, Nanjoh claims an AB measurement method comprising
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`treating an irrigated nasal mucosa specimen (claim 20) with a solubilizer (extraction liquid) and measuring
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`the AB quantitatively (claim 3). Nanjoh teaches this method in the context of diagnosing AD (paragraphs
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`3-10). This clearly indicates that methods were known and being practiced at the time of the instant
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`invention for extracting and measuring AB from intranasal specimens for diagnosing AD, supporting the
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`assertion that these methods were routine and conventional. In another example, Yamagishi (citation 9
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`on IDS filed 1/12/15) teaches pretreating an intranasal specimen collected from a nasal cavity (p. 421,
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`CZ: “olfactory mucosa was obtained...by means of the special biopsy instruments we routinely use in our
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`Application/Control Number: 14/374,181
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`Art Unit: 1649
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`Page 7
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`small clinic”; p.422, C1: “the specimens were fixed...dehydrated...and embedded”). Yamagishi teaches
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`detecting tau in the sample (table on page 425), comparing this value with predetermined values
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`(compared to healthy controls, see table on p.425; compared to positive and negative control values to
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`validate the assay, see p.422 C1 -2), and displaying the comparisons (see figures and table throughout).
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`Yamagishi teaches this method for its use as a definitive diagnosis of AD (abstract). Thus, contrary to
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`Applicant’s assertion that tau has not been readily detected in an intranasal specimen, Yamagishi, which
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`was discussed in depth in the prior action, indicates that such measurements were known in the art and
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`being developed for the same purpose. It is noted that Yamagishi also detected AB in the intranasal
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`specimens as discussed previously. These are also clearly immunoassays as antibodies were employed
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`in the detection step. Finally, Matson (US 6194217; cited on IDS), also discussed in the previous action,
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`teaches using intranasal specimens to measure both AB and tau and states “the possibility of using
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`biopsy of nasal epithelium as a clinical marker of Alzheimer's disease during life was suggested" (C19
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`L40-48). Matson uses a saline suspension of mucosa (extraction liquid). Thus, the evidence supports that
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`such measurements were well-known and routine in the art, even within the context of diagnosing AD.
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`Applicant argues that, in addition, the claims calculate a square root value from the sum of the
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`squares of the detected tau protein and A8 for comparison. First, it is noted that the claims do not reflect
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`this assertion: only the square of AB values are used and not the square root of the sum of squares of the
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`AB value. In either case, Applicant does not elaborate on this statement to indicate why this is
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`significantly more than the judicial exception. To the contrary, as discussed above and previously, the
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`calculation is a description of the judicial exception (an abstract idea and/or natural correlation). Thus,
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`reciting this calculation does not offer significantly more. This fact pattern can be compared to the facts in
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`Diehr, 450 Us at 184. In Diehr, a natural correlation (also a mathematical representation of said
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`correlation) was claimed. However, in Diehr, the data was gathered, the equation was utilized, and an
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`article was transformed; raw, uncured rubber was transformed into a different state. It is this
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`transformation--the application of the law of nature--which the Court found patentable. In the instant case,
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`no such transformation occurs. The patient either has AD or not prior to the method, and the method does
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`not alter this. Detecting the levels, even in the specific ways claimed, does not transform or alter those
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`Application/Control Number: 14/374,181
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`Art Unit: 1649
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`Page 8
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`levels in anyway but is rather a necessary step to recognizing the correlation and, once recognized, the
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`claims require no more. The instant case is more akin to the fact patterns of Mayo and Alice (see federal
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`register citation above for specific case citations). Instructions at a high level of generality to apply a
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`natural correlation, even with the use of a generic computer performing generic functions or appending
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`well-understood, routine and conventional activities previously known to the industry does not add
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`significantly more to the judicial exception. In Mayo, metabolites were measured and the claims added no
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`more than instructions at a high level of generality regarding what to do with that information. Nothing was
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`transformed and the claim recited no more than the judicial exception itself along with elements already
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`engaged in by those in the field.
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`Therefore, claims 3-4, 7-10, 12, and 14 are drawn to patent ineligible subject matter.
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`No claim is allowed.
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`Conclusion
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`Applicant's amendment necessitated the new ground(s) of rejection presented in this Office
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`action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of
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`the extension of time policy as set forth in 37 CFR 1.136(a).
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`A shortened statutory period for reply to this final action is set to expire THREE MONTHS from
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`the mailing date of this action.
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`In the event a first reply is filed within TWO MONTHS of the mailing date
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`of this final action and the advisory action is not mailed until after the end of the THREE-MONTH
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`shortened statutory period, then the shortened statutory period will expire on the date the advisory action
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`is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of
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`the advisory action.
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`In no event, however, will the statutory period for reply expire later than SIX
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`MONTHS from the date of this final action.
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`Any inquiry concerning this communication or earlier communications from the examiner should
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`be directed to ADAM M. WEIDNER whose telephone number is (571)272-3045. The examiner can
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`normally be reached on Monday - Friday, 800 - 1630 EST.
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`Application/Control Number: 14/374,181
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`Art Unit: 1649
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`Page 9
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`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor,
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`Jeffrey Stucker can be reached on 571 -272-091 1. The fax phone number for the organization where this
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`application or proceeding is assigned is 571-273-8300.
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`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
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`Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should
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`you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC)
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`at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative
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`or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-
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`1000.
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`/A. M. W./
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`Examiner, Art Unit 1649
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`/GREGORY S EMCH/
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`Primary Examiner, Art Unit 1649
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`