`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`PO. Box 1450
`Alexandria1 Virginia 22313- 1450
`www.uspto.gov
`
`APPLICATION NO.
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`
`
`
`
` F ING DATE
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`FIRST NAMED INVENTOR
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`ATTORNEY DOCKET NO.
`
`
`
`
`
`CONF {MATION NO.
`
`13/355,458
`
`01/20/2012
`
`Ian Gibbons
`
`30696—733201
`
`1056
`
`Theranos, Inc.
`1601 S. California Avenue
`Palo Alto, CA 94304
`
`REYES, CHRISTOPHER R
`
`ART UNIT
`
`1639
`
`PAPER NUMBER
`
`
`
`
`NOT *ICATION DATE
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`DELIVERY MODE
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`07/08/2014
`
`ELECTRONIC
`
`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.
`
`Notice of the Office communication was sent electronically on above—indicated "Notification Date" to the
`following e—mail address(es):
`
`docketing @theranos.c0m
`
`PTOL—90A (Rev. 04/07)
`
`

`

`
`
`Applicant(s)
`Application No.
` 13/355,453 GIBBONS ET AL.
`
`Examiner
`Art Unit
`AIA (First Inventorto File)
`Office Action Summary
`
`1639CHRISTOPHER REYES first“
`
`-- 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 3 MONTHS FROM THE MAILING DATE OF
`THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR 1.136(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
`
`-
`-
`
`Status
`
`1)IXI Responsive to communication(s) filed on 06 January 2014 and 24 June 2013.
`[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.
`
`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.
`
`Disposition of Claims*
`
`5)|XI Claim(s) 1-35 37-64 72-82 95 99-104 107 and 108 is/are pending in the application.
`5a) Of the above claim(s) 1-33,38-64,72-82 and 100 is/are withdrawn from consideration.
`6)|:l Claim(s) _ is/are allowed.
`
`7)IZ| Claim(s) 34 35 37 95 99 101- 104 107 and 108 is/are rejected.
`8)I:I Claim(s)_ is/are objected to.
`
`9)|:l Claim((s)
`are subject to restriction and/or election requirement.
`* If any claims have been determined allowable, you may be eligible to benefit from the Patent Prosecution Highway program at a
`
`participating intellectual property office for the corresponding application. For more information, please see
`htt
`://www.usoto. ov/ atents/init events"
`
`
`
`h/index.‘3 , or send an inquiry to PRI-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)|:l All
`1.|: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
`
`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 20140416
`
`

`

`Application/Control Number: 13/355,458
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`Page 2
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`Art Unit: 1639
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`DETAILED ACTION
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`The present application is being examined under the pre-AIA first to invent provisions.
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`Responsive to communications entered 06 January 2014 and 24 June 2013.
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`Claims 1-35, 37-64, 72-82, 95, 99-104, 107, and 108 are pending.
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`Claims 36, 65-71, 83-94, 96-98, 105, and 106 are canceled.
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`Claims 1-33, 38-64, 72-82, and 100 are withdrawn.
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`Claims 34, 35, 37, 95, 99, 101 -104, 107 and 108 are herein examined on the merits.
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`Election/Restrictions
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`Applicant’s election of the species: (i) the sample is suitable for storage in a
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`pipette tip and the sample is biological in nature; (ii) the sample is imaged within a
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`pipette tip; and (iii) the illumination source is located on an opposing side of the pipette
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`tip as the imaging device in the reply filed on 06 January 2014 is acknowledged.
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`Because applicant did not distinctly and specifically point out the supposed errors in the
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`restriction requirement, the election has been treated as an election without traverse
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`(MPEP § 818.03(a)).
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`Species election requirements 2 and 4 as set forth in the office action mailed 04
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`November 2013 are withdrawn in view of the cancellation of claims 92, 97, and 98.
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`Claim 100 is withdrawn from further consideration pursuant to 37 CFR 1.142(b)
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`as being drawn to a nonelected species, there being no allowable generic or linking
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`claim. Election was made without traverse in the reply filed on 06 January 2014.
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`Withdrawn Objection(s) and/or Rejection(s)
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`

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`Application/Control Number: 13/355,458
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`Page 3
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`Art Unit: 1639
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`The objection to claims 34 and 35 because of informalities is withdrawn in view of
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`Applicant's amendments.
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`The rejection of claims 34 and 35 under 35 U.S.C. 102(b) as being anticipated by
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`PG-Pub 20030138140 (to Marcelpoil) is withdrawn in view of Applicant’s amendments.
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`The rejection of claim 36 under 35 U.S.C. 103(a) as being unpatentable over
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`Marcelpoil in view of Tholouli et al (2006 Biochemical and Biophysical Research
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`Communications 348: 628-636) and PG-Pub 20080038771 (to Taylor) is withdrawn in
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`view of applicant's cancellation thereof.
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`Maintained Claim Rejections - 35 USC § 103
`
`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all
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`obviousness rejections set forth in this Office action:
`
`(a) A patent may not be obtained though the invention is not identically disclosed or described as set
`forth in section 102 of this title, if the differences between the subject matter sought to be patented and
`the prior art are such that the subject matter as a whole would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which said subject matter pertains.
`Patentability shall not be negatived by the manner in which the invention was made.
`
`The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148
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`USPQ 459 (1966), that are applied for establishing a background for determining
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`obviousness under 35 U.S.C. 103(a) are summarized as follows:
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`1.
`
`2.
`
`3.
`4.
`
`Determining the scope and contents of the prior art.
`Ascertaining the differences between the prior art and the claims at issue.
`Resolving the level of ordinary skill in the pertinent art.
`Considering objective evidence present in the application indicating
`obviousness or nonobviousness.
`
`This application currently names joint inventors.
`
`In considering patentability of
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`the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of
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`Page 4
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`Art Unit: 1639
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`the various claims was commonly owned at the time any inventions covered therein
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`were made absent any evidence to the contrary. Applicant is advised of the obligation
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`under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was
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`not commonly owned at the time a later invention was made in order for the examiner to
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`consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g)
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`prior art under 35 U.S.C. 103(a).
`
`Claims 34 and 35 are rejected under 35 U.S.C. 103(a) as being unpatentable
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`over US 20030138140 (hereinafter Marcelpoil) in view of Tholouli et al (2006
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`Biochemical and Biophysical Research Communications 348: 628-636) and PG-Pub
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`20080038771 (hereinafter Taylor).
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`Regarding claims 34 (steps (a), (c), and (d)) and 35, Marcelpoil teaches an
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`image-based method of detecting and quantitating molecular species of interest in a
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`sample, as indicated in paragraph [0092] (Le. a method for characterizing an analyte
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`suspected to be present in a sample). Paragraphs [0069]-[0070] indicate recording an
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`image with a 3CCD RGB camera (e.g. an imaging device) such that the image is
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`comprised of a plurality of pixels arranged in a Cartesian coordinate system wherein
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`intensity values are measured at each pixel. Paragraph [0071] teaches that intensity
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`values are measured in red, green, and blue (per instant claim 35) channels for each
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`pixel (i.e. the obtained image is a digital image that comprises at least a two-
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`dimensional array of pixels wherein each pixel comprises a plurality of intensity values,
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`each of which corresponds to a distinct detection spectral region). Figure 1 and
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`paragraph [0053] indicate that the device comprises a computer which, as indicated in
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`Page 5
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`paragraph [0054], is configured to be capable of analyzing the image with respect to
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`each of the red, green, and blue channels (i.e. the method steps are executed with the
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`aid of a programmable device).
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`Paragraph [0070] teaches that the intensity values measured for each pixel may
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`be applied directly in a calculation of a concentration using the well-known Beer-
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`Lambert law as described in equation (1) at the end of paragraph [0061]. The Beer-
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`Lambert law, and derivatives thereof, define predetermined sets of values on the basis
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`of a known path length and known extinction coefficients (e.g. over a range of
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`observable intensity values in an experiment (a set predetermined by the technical
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`limitations of an apparatus), there is a range of concentrations that may be calculated (a
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`set predetermined by the Beer-Lambert law)). Thus the reference teaches a step of
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`correlating with the aid of a programmable device the obtained intensity values with a
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`predetermined set of values. Further, paragraph [0071] teaches that the method
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`handles a range of values that is defined by a minimal intensity value of a "black image"
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`that "will have an intensity value approaching 0" in each channel and white light image
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`that defines a maximum intensity value that may be recorded in each channel, and thus
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`defines a dynamic range for each detection spectral region. Regarding step (d) of
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`instant claim 34:”predicting the presence of said analyte based on said correlating...”
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`the Beer-Lambert law allows calculation of concentration given optical density,
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`extinction coefficient, and path length. Since the latter three values are known or
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`measured in the reference, it is clear that application of this method suggests being
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`used in a step of predicting the quantity of said analyte in the sample.
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`Page 6
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`Art Unit: 1639
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`Marcelpoil does not teach selection and illumination of the sample by an
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`illumination wavelength concurrently with obtaining the digital image as in claim 34
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`(step(b))-
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`Tholouli et al is drawn throughout the reference to a method of imaging a tissue
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`sample using quantum dot-labeled oligonucleotides as described in the abstract.
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`Regarding claim 34, Tholouli’s method involves excitation of the sample at 490
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`nm (e.g. selecting an illumination wavelength and illuminating the sample with selected
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`illumination wavelength), as described under the heading “Spectral imaging" on page
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`630. While illuminating the quantum dot-labeled sample with light at 490 nm, Tholouli et
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`al indicates recording images (e.g. obtaining a digital image) of the sample over a
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`detection range covering 450 to 720 nm (which includes blue, green, and red
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`wavelengths - distinct detection spectral regions), wherein an image is recorded every 5
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`nm within that range such that each image contains the complete spectral information
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`for every pixel at a given wavelength. This ensemble of images is subsequently
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`combined into a spectral 'cube' that indicates spectral information at each pixel across
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`all wavelengths measured.
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`It would have been prima facie obvious to one of ordinary skill in the art at the
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`invention was made to apply quantum dots and multispectral imaging in the manner of
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`Tholouli to the imaging method of Marcelpoil.
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`One of ordinary skill would have been motivated to apply quantum dots and
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`multispectral imaging in the manner of Tholouli to the imaging method of Marcelpoil
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`because Tholouli et al indicates in the first paragraph of the left column on page 629
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`that quantum dots possess several desirable properties that make them well suited
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`toward bioimaging of tissues samples (imaging tissues samples being of interest of
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`Marcelpoil; see paragraph [0057]) including high fluorescence efficiency, long
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`fluorescence lifetime, an excitation wavelength that is constant, and a detection
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`wavelength that is tunable. Thus per Tholouli et al, quantum dots are "near-optimal for
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`many fluorescent applications." Additionally, whereas Marcelpoil only implements
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`detection of red, blue, and green wavelengths (e.g. Marcelpoil uses a 3CCD RGB
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`camera as in paragraph [0069]), Tholouli's approach is spectral and implements
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`detection over a greater range of wavelengths (see abstract and penultimate paragraph
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`of left column on page 630 Tholouli et al). Taylor indicates in paragraphs [0082]-[0085]
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`that application of a spectral imaging process as in Tholouli represents a technological
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`improvement over 3CCD RGB device-based imaging as applied in Marcelpoil since
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`spectral imaging beneficially provides an enhancement in accurately distinguishing
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`colors and features, and allows for distinguishing between more than 3 colors.
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`One of skill in the art would have had an expectation of success in applying
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`quantum dots and multispectral imaging in the manner of Tholouli to the imaging
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`method of Marcelpoil because both references concern imaging biological samples (see
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`paragraph [0080] and Figure 11 of Marcelpoil, and Figure 2 of Tholouli et al), and the
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`approach to image deconvolution applied in Tholouli et al is similar to the image
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`deconvolution method found in Marcelpoil. Compare the penultimate paragraph of the
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`left column on page 630 of Tholouli et al ("a spectral library comprising the spectra of
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`tissue autofluorescence and that of each quantum dot used is created" and
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`subsequently applied in spectral unmixing) and paragraph [0075] of Marcelpoil (“After
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`the model for the combination of dyes used for the particular protocol has been
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`completed, the model may then be applied to unknown histological samples”).
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`Paragraph [0085] of Taylor also indicates that Lambert-Beer law analysis relating
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`concentration to absorbance is also applied in a linear unmixing algorithm regardless of
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`whether the images are collected as RGB images (as in Marcelpoil) or as multispectral
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`datasets (as in Tholouli). Accordingly, the modifications suggested by Tholouli et al fall
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`well within the scope of technology of interest to Marcelpoil.
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`Response to Arguments
`
`The remarks accompanying the response entered 24 June 2013 argue: (i) not all
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`elements are taught by the cited references; (ii) the disclosure of the cited references
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`teaches away from the claimed invention.
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`Applicant’s arguments have been fully considered but they are not deemed
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`persuasive for the following reasons.
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`Specifically regarding argument (i), the reply contends in the last three
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`paragraphs on page 13 that neither Marcelpoil, Tholouli et al, nor Taylor teaches or
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`suggests “selecting an illumination wavelength based on the analyte suspected to be
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`contained in the sample.” In this vein, applicant is respectfully invited to the penultimate
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`paragraph of the left column on page 630 of Tholouli et al which teaches selecting using
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`an excitation filter (e.g. selecting an illumination wavelength), which provides an
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`excitation wavelength for visualizing quantum dots conjugated to oligonucleotide probes
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`Page 9
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`Art Unit: 1639
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`assaying gene expression (see second paragraph of right column on page 630, and
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`abstract). Thus, contrary to the assertion of the reply, Tholouli et al does in fact teach
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`selecting an illumination wavelength (e.g. an excitation wavelength) based on the
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`analyte suspected to be contained in the sample (e.g. selecting an excitation
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`wavelength that corresponds to a quantum dot coupled to a probe designed for
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`detection of said analyte) and illuminating the sample with the selected illumination
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`wavelength.
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`Specifically regarding argument (ii), the reply contends in the last two paragraphs
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`on page 13 and the first paragraph on page 14 that the automatic collection of a series
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`of images at different wavelengths wherein the series of images covers a range of
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`wavelengths as in Tholouli and Taylor teaches away from "selecting a particular
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`illumination wavelength based on an analyte suspected to be contained the sample.” It
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`is noted that the features upon which applicant relies (i.e., selecting a particular
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`illumination wavelength) are not recited in the rejected claim(s). Although the claims are
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`interpreted in light of the specification, limitations from the specification are not read into
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`the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQZd 1057 (Fed. Cir. 1993).
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`Moreover, the examiner respectfully submits that the assertion of “teaching away” relies
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`on a misinterpretation of the teachings of Tholouli et al and Taylor.
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`In this vein,
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`Applicant is respectfully invited to the penultimate paragraph of the left column on page
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`630 of Tholouli et al and paragraph [0084] of Taylor. From these sections of the cited
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`references, it is clear that the automatic image collection is a detection step, not a step
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`of providing an illumination wavelength.
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`In other words, these automatic image
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`collection steps do not indicate anything about illumination at all, but merely are directed
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`to a means of recording a digital image (e.g. obtaining a digital image per claim 34,
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`step(b)). Furthermore, the citation to Tholouli et al demonstrates that in addition to this
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`automatic image collection (e.g. detection of images in 5 nm wavelength intervals over
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`the wavelength range 450 nm to 720 nm), there is also a step of selecting an
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`illumination wavelength (e.g. the Leitz Diaplan fluorescence microscope has a 490 nm
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`excitation filter).
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`In other words, not only does the automatic image collection procedure
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`say nothing about illumination (and therefore cannot teach away from selecting an
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`illumination wavelength based on the analyte suspected to be contained in the sample),
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`Tholouli explicitly approves of the use of automatic image collection with a step of
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`selecting an illumination wavelength based on an analyte suspected to be contained in
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`the sample (e.g. oligonucleotide probes coupled to quantum dots and hybridized with
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`targets), thereby teaching toward the presently claimed subject matter.
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`Claim 37 is rejected under 35 U.S.C. 103(a) as being unpatentable over
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`Marcelpoil in view of Tholouli et al and Taylor as applied to claims 34 and 35 above,
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`and further in view of Resch-Genger et al (September 2008 Nature Methods 5: 763-
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`775).
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`Marcelpoil in view of Tholouli et al and Taylor are relied on as above.
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`Additionally regarding claim 37, Tholouli et al teaches the use of multiple
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`quantum dots. The section entitled “Multiplexing” on page 630 references multiple
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`quantum dots, and the section entitled “Reagents" on page 629 indicates that quantum
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`dots with different emission spectra were used. As illustrated in Figures 4 and 5, such
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`multiplexing provides additional information regarding (e.g. predicts the presence of)
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`cells in bone marrow samples (e.g. analyte). Since Tholouli only describes one
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`excitation wavelength, it is presumed that all quantum dots used adequately absorb at
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`the selected excitation wavelength.
`
`Marcelpoil in view of Tholouli et al and Taylor do not explicitly teach the
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`illumination of the sample by a second wavelength as in claim 37.
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`Resch-Genger reviews quantum dots (QDs) and organic dyes.
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`Regarding claim 37, Table 2 on page 766 of Resch-Genger provides a
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`comparison of QDs and organic dyes. Figure 1 of Resch-Genger supports the
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`presumption that the quantum dots of Tholouli et al all adequately absorb at the
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`selected excitation wavelength (note the similarity absorption spectra for the QDs of
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`different sizes and composition, and in different solvents)
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`It would have been prima facie obvious to one of ordinary skill in the art at the
`
`time the invention was made to substitute the quantum dots of Tholouli with organic
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`dyes as suggested by Resch-GengerFurther regarding claim 37, whereas different
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`quantum dots have similar absorption spectra and may be excited using a single
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`wavelength, organic dyes may have very different absorption spectra and require
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`excitation with different wavelengths. See Figure 1(d-f) of Resch-Genger; for instance,
`
`whereas Cy3 absorbs significantly at 500 nm, Cy5 absorbs virtually no light at this
`
`wavelength. Thus using multiple different organic dyes in place of the multiple different
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`QDs of Tholouli et al would require recording multiple sets of images, wherein each set
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`is recorded concurrently with illumination of the sample by a different wavelength
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`selected specifically for the excitation of a particular organic dye.
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`One of ordinary skill would have been motivated to substitute the quantum dots
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`of Tholouli with organic dyes because as indicated by Resch-Genger in the second
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`paragraph of the right column on page 770, it is not known to what extent there is
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`leakage of toxic substances from the cores of ODs (as applied in Tholouli). On the
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`other hand, the second paragraph of the right column on page 770 that “cytotoxicity
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`data for many traditional dyes are available," and in general their cytotoxicity is not a
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`problem.
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`In other words, Resch-Genger indicates that whereas ODs may introduce
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`unknown variables into an experiment (such as leakage of toxic substances (e.g. Cd2+)
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`leaking from the cores of ODs as probes), organic dyes beneficially have been well-
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`explored, and their activity in a system is predictable. Also see Table 2 of Resch-
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`Genger which further indicates lack of information in regard to the means by which
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`quantum dots may be bound to biomolecules, the application of ODs in FRET
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`experiments, and signal amplification techniques involving ODs whereas organic dyes
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`have been well-described in regard to these topics.
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`One of ordinary skill would have had an expectation of success in substituting the
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`quantum dots of Tholouli with organic dyes because as indicated in the penultimate
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`paragraph of the right column on page 770 of Resch-Genger, organic dyes are suited
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`for acquiring reliable and comparable fluorescence measurements, and their application
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`is less challenging that the quantum dots applied in Tholouli.
`***
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`

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`Application/Control Number: 13/355,458
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`Page 13
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`Applicant does not offer further arguments regarding the above obviousness
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`rejection(s) beyond what was set forth with regard to the first 35 U.S.C. § 103 rejection,
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`over Marcelpoil in view of Tholouli et al and Taylor above. To the extent that Applicant is
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`merely repeating their previous argument, the Examiner contends that those issues
`
`were adequately addressed in the above section(s), which is/are incorporated in their
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`entireties herein by reference.
`
`New Claim Rejections - 35 USC § 103
`
`Claims 34, 35, 37, 95, 99, 101, 102, 103, 104, 107, and 108 are rejected under
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`pre-AlA 35 U.S.C. 103(a) as being unpatentable over US 6013528 (hereinafter Jacobs)
`
`in view of Marcelpoil
`
`Jacobs is drawn throughout the reference and especially the title, equations 1)-
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`3), 18-25 of col. 11, figures programming a spectrometer with an algorithm for “through-
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`the-tip” analysis of fluid samples which may contain, for instance hemoglobinMore
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`particularly Regarding claim 34 (steps (b)-(d)), Jacobs teaches in lines 25-45 of column
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`3 a method wherein near-infrared and adjacent visible radiation is passed through a
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`liquid to test for target substances, such as albumin and glucose. Also see lines 45-55
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`of column 9 wherein Jacobs relates absorption values at particular wavelengths to the
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`concentrations of particular target substances, including hemoglobin (Hb). Jacobs
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`indicates that each set of equations only faithfully indicates true concentration values
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`over certain concentration regimes; thus Jacobs indicates that each predetermined set
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`of concentration values and absorption/intensity values defines a dynamic range (e.g.
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`each set is applied only over the concentration ranges (dynamic range) with which it
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`produces a linear/ true relationship between absorbance values and calculated
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`concentration values). It is noted that absorbance is inherently an intensity value of light.
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`Regarding claim 35, Jacobs suggests in lines 50-55 of column 3 that radiation
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`applied in the invention is selected from the range of wavelengths spanning 400 to 2500
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`nm. This range includes wavelengths for red (620-750 nm), green (495-570 nm), and
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`blue (450-495 nm). Jacobs thus suggests a plurality of intensity values (reported as
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`absorbance values) for these three colors/ detection spectral regions.
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`Regarding claim 37 (in part), as in lines 1-3 of column 4, the analysis
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`implemented by Jacobs is spectrophotometric analysis at various bands (e.g. the
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`analysis requires illumination and detection of absorbance wavelengths at multiple
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`wavelengths). Jacobs thus teaches selecting another illumination wavelength (instant
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`step (a)), illuminating the sample with the other selected illumination wavelength (instant
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`step (b)); and predicting the presence of an analyte in the sample on the basis of
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`intensity values collected using the first selected wavelength and the second selected
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`wavelength (instant step (d)). See the equations in lines 45-55 of column 9 which each
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`use absorbance values at multiple wavelengths to calculate the concentration of
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`hemoglobin, for example.
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`Regarding claim 95, Jacobs indicates in line 43 of column 3 that the sample may
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`be blood or urine [a biological sample suitable for storage in a pipette tip; elected
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`species].
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`Regarding claim 99 (in part), as indicated by the title and lines 45-50 of column 5
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`of Jacobs, the sample is in a pipette tip while absorbance signals are measured.
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`Regarding claim 101, as is necessary for absorbance measurements, Jacobs
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`illustrates in figure 2A that an illumination source (element 98) is located on an opposing
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`side of the pipette tip as an imaging device (element 98’) [elected species]. Element 98
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`and 98’ are fiber optic components. See lines 42-45 of column 5.
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`Regarding claims 102-104, the pipette tip is indicated by element 48 in Figure 2A
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`(see lines 913 of column 5). The pipette tip has a generally conical shape, has two
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`open ends (e.g. one end connected to aspirator means, the other end able to take in
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`sample), and the first open end (e.g. the portion closer to element 111) has a greater
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`diameter than a second open end (e.g. the portion closer to element 83).
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`Regarding claims 107 and 108, as illustrated by the equations in lines 45-55 of
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`column 9, Jacobs is directed toward quantitating (e.g. predicting the quantity of)
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`analytes of interest.
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`Jacobs does not teach obtaining a digital image of the sample with an imaging
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`device, wherein the digital image comprises at least a two-dimensional array of pixels,
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`and wherein each pixel comprises a plurality of intensity values, each of which
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`corresponds to a distinct spectral region, as in claim 34 (steps(a and b)), claim 37 (step
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`(c)), and claim 99.
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`Marcelpoil is drawn to an algorithm for modeling a dye using images of a
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`sample. See paragraph [0018].
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`Regarding claims 34 (step (a)), 37 (step (c)), and 99, Marcelpoil teaches
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`throughout the reference, and especially in paragraph [0021], a procedure wherein a
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`digital image of a sample is recorded with an imaging device (such as with a RGB color
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`CCD camera; see paragraph [0024]) wherein the digital image comprises at least a two
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`dimensional array of pixels (see figures 11A-11E and corresponding description in
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`paragraphs [0041]-[0043], indicating that the images recorded by the imaging device
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`are at least two dimensional, and paragraphs [0069]-[0070] which indicate representing
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`an image as a Cartesian coordinate system with (x,y) coordinates), wherein each pixel
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`comprises a plurality of intensity values, each of which corresponds to a distinct
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`detection spectral region (as in paragraphs [0018] and [0021], each pixel has a color
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`defined by a RGB triplet which represents transmittance of red, green, and blue
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`wavelengths for each pixel; also see paragraph [0071]).
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`It would have been prima facie obvious to one of ordinary skill in the art at the
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`time the invention was made to replace the fiber optic-based detection of Jacobs with
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`the color-CCD based detection of Marcelpoil. Regarding claim 99, please note the test
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`for obviousness is not that the claimed invention must be expressly suggested in any
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`one or all of the references. Rather, the test is what the combined teachings of the
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`references would have suggested to those of ordinary skill in the art. See In re Keller,
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`642 F.2d 413, 208 USPQ 871 (CCPA 1981). Here, it is the combination of the through-
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`the-tip analysis of Jacobs (see title) and the digital image-based analysis of Marcelpoil
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`(see paragraph [0018]) which would have suggested to the skilled artisan a method step
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`acquiring a digital image of a sample while the sample is disposed in a pipette tip.
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`One of ordinary skill in the art would have been motivated to replace the fiber
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`optic-based detection of Jacobs with the color-CCD based detection of Marcelpoil
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`because as indicated in paragraph [0025] of Marcelpoil, a color-CCD based detection
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`applied in the manner of Marcelpoil beneficially enables quantification of more species
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`of interest than possible with Jacobs by overcoming limiting factors that are not
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`addressed by Jacobs, such as spectral overlapping and/or interfering colored
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`substances overlapping in space and/or challenges associated with calibration
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`particularities.
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`One of ordinary skill would have had a reasonable expectation of success in
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`replacing the fiber optic-based detection of Jacobs with the color-CCD based detection
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`of Marcelpoil because Jacobs and Marcelpoil both concern applying absorbance/
`
`transmission values to quantitate analytes. See abstract of Jacobs and of Marcelpoil
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`and lines 45-55 of column 9 of Jacobs. Additionally, evidence provided by paragraph
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`[0030] of Redfern (drawn to using a pipette tip as a containment vessel during
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`spectrophotometric analysis of a liquid sample contained therein; see paragraphs [