`
`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
`Alexandria1 Virginia 22313- 1450
`www.uspto.gov
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`APPLICATION NO.
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`
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` F ING DATE
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`FIRST NAMED INVENTOR
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`ATTORNEY DOCKET NO.
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`
`
`
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`CONF {MATION NO.
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`13/646,784
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`10/08/2012
`
`Masaya TAMURA
`
`MAT—10579US
`
`1082
`
`EXAMINER
`RATNERPRESTIA —
`09’3”“ —
`7590
`52473
`PO. BOX 980
`MARCSISIN, ELLEN JEAN
`VALLEY FORGE, PA 19482-0980
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`PAPER NUMBER
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`ART UNIT
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`1678
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`
`
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`NOT *ICATION DATE
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`DELIVERY MODE
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`09/3 0/2014
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`ELECTRONIC
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`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.
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`Notice of the Office communication was sent electronically on above—indicated "Notification Date" to the
`following e—mail address(es):
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`ptocorrespondence @ratnerprestia.c0m
`
`PTOL—90A (Rev. 04/07)
`
`

`

`
`
`Applicant(s)
`Application No.
` 13/646,784 TAMURA ET AL.
`
`
`AIA (First Inventorto File)
`Art Unit
`Examiner
`Office Action Summary
`
`
`Ellen J. Marcsisin a?” 1678
`-- 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
`
`-
`-
`
`Status
`
`1)IXI Responsive to communication(s) filed on 07/30/2014.
`[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
`
`
`; 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) 1-8 and 10-18 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) 1-Band10- 18is/are rejected.
`8)IZ| Claim(s) 1, Band 17is/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
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`
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`://www.usoto. ov/ atentS/init events"
`h/index.‘s orsend an inquiry to PF"I-Ifeedback{<‘buspto.qov.
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`htt
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`Application Papers
`
`10)I:I The specification is objected to by the Examiner.
`11)|Z| The drawing(s) filed on 10/08/2012 is/are: a)IXI 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)IZI 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)le 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.
`33.le 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) D Notice of References Cited (PTO-892)
`Paper No(s)/Mai| Date.
`.
`.
`—
`4) I:I Other'
`2) E InformatIon DIscIosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`
`Paper No(s)/Mai| Date 10/08/2012 05/27/2014.
`
`US. Patent and Trademark Office
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20140918
`
`

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`Application/Control Number: 13/646,784
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`Page 2
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`Art Unit: 1678
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`DETAILED ACTION
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`1.
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`The present application is being examined under the pre—AIA first to invent provisions.
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`Status of the Claims
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`2.
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`Claims 1, 8, 10—18 have been amended. Claim 9 and 19—20 have been cancelled. Claims
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`1—8 and 10—18 are pending and subject to examination below.
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`Priority
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`3.
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`The instant application is a continuation in part of PCT/JP2011/002567, filed on
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`05/09/2011. Acknowledgment is made of the claim of foreign priority to application No. 2010—
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`10980, filed 05/12/2010 in Japan.
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`Withdrawn Rejections/Objections
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`4.
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`The objections to claims 1 and 17—19 have been withdrawn in response to Applicant’s
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`amendments to the claims and in view of the cancellation of claim 19.
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`The previous rejections of claims under 35 U.S.C. 103(a) have been withdrawn in
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`response to Applicant’s amendments to the claims.
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`New Grounds of Rejection/Objection
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`Claim Objections
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`5.
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`Claims 1 and 8 are objected to because of the following informalities: The claims recite
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`(see claim 1, lines 6—8 and claim 8, lines 6—8) "wherein a hollow region provided between the
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`first metal layer and the second metal layer", said statement being grammatically incorrect, as it
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`appears the word “is” is missing after the word “region”. Appropriate correction is required.
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`Claim 17 recites the limitation "the plurality of analyte capturing bodies" in line 2,
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`previously referred to as “analyte capturing bodies” in claim 1. It appears, Applicant intends to
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`refer to “the analyte capturing bodies”, since claim 1 does not recite the word “plurality” in order
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`to provide antecedent basis for the limitation as amended.
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`Claims 1, l6 and 17 are objected to because the claims recite the limitation “physically
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`adsorbed to at least one of below the first metal layer and above the second metal layer”, such
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`that it is unclear to exactly what “one” refers to. Put another way, it is unclear to what exactly the
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`capturing bodies are physically adsorbed to.
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`Claim Rejections - 35 USC § 112
`
`The following is a quotation of 35 USC. 112(b):
`(b) CONCLUSION.7The specification shall conclude with one or more claims particularly pointing
`out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the
`invention.
`
`The following is a quotation of 35 USC. 112 (pre—AIA), second paragraph:
`The specification shall conclude with one or more claims particularly pointing out and distinctly
`claiming the subject matter which the applicant regards as his invention.
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`6.
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`Claims 1 is rejected under 35 USC. 112(b) or 35 USC. 112 (pre—AIA), second
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`paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject
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`matter which the inventor or a joint inventor, or for pre—AIA the applicant regards as the
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`invention.
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`Claim 1 recites “wherein part of the analyte capturing bodies are desorbed and float
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`between the first metal layer and the second metal layer”, and prior the claim recites the
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`antibodies are adsorbed. It is noted that the claim is drawn to a product and not a method; as such
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`the limitation is not clearly describing the status of the capturing bodies of the product. It appears
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`Applicant’s intended meaning is that part of the capturing bodies can be desorbed, for example
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`interpreted to mean upon addition of specimen (e. g. instant claims 17 and 18); however, if this is
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`Applicant's intention, such a limitation is considered to be drawn to the intended use and is not
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`considered to specifically limit a product.
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`Claim Rejections - 35 USC § 103
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`The following is a quotation of pre—AIA 35 USC. 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.
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`Claims 1, 6—7, 17 are rejected under pre—AIA 35 USC. 103(a) as being unpatentable over
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`Song et al., US 2010/0097611A1 in view of Cohen et al. US PG Pub No. 2002/0196435A1; or
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`rather in the alternative as being unpatentable over Song et al. in view of Tung et al. US PG Pub
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`No. 2002/0058031A1.
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`Song et al. teach a long range surface plasmon optical waveguide sensor (see e. g. abstract
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`and entire document) which meets the structural limitations of the claims as described, see e. g.
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`para [0011], in that the sensor comprises a metal thin film and a metal strip such that each are
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`spaced apart by a predetermined interval, also comprising a channel in between so the metal
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`surfaces interface with the channel. Specifically see e. g. Figure 5, and also, paras [0039]—[0040],
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`Figure 5 embodiment 113 is the metal thin film, 115 indicates the metal strip, 117 is the channel
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`(i.e. hollow region). The sensor of Song et al. is used with an electromagnetic wave source; see
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`e. g. para [0064], halogen lamp, light emitting diode, laser or the like. The metal strip generates a
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`surface plasmon between the metal layers. The sensor is equipped with a detector that
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`quantitatively or qualitatively measures the change of wavelength propagating by the specimen
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`(i.e. wave generated in the channel where specimen is) (see also specifically para [0070],
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`measure a change of wavelength, change of mode size, change of intensity, etc.). See para
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`[0073], Song et al. also specifically teach that both the metal thin film and the metal strip are
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`sufficiently constrained by the long range surface plasmon to thereby propagate an
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`electromagnetic wave (i.e. propagate along the channel).
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`Furthermore, Song et al. teaches that analyte capturing bodies may be physically
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`adsorbed between the metal layers, see specifically para [0059]. The reference further teaches
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`that the sensor may be used as immunosensor, wherein biological material such as an antibody
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`(i.e. an analyte capturing body) is immobilized (i.e. adsorbed) on the exposed one side surface of
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`the metal strip. Also Song et al. teach at para [0075] that it is possible to fabricate a sensor of
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`various sizes such as small—sized or light—weight systems.
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`Song et al. does not specifically teach wherein the analyte capturing bodies are desorbed
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`and float between the first metal layer and the second metal layer.
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`Cohen et al. teach a microfluidic assay device comprising microfluidic circuitry (i.e.
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`hollow cavities, referred to as chambers, which appear to be channels/paths) (see e. g. entire
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`document and Figure 1), wherein the channel of the device are directly observed by optical
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`reader (see e. g. para [0060], i.e. optically scanning a chamber of said device to observe
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`reaction/assay). See e. g. para [0074] Cohen et al. teach biological reaction occurs in an entry
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`chamber (i.e. cavity) of the device. Specifically at para [0075] Cohen et al. teach assay reagent or
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`bioactive agent may include freeze dried material, which may for example be freeze dried in the
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`entry chamber; that said material may dissolve upon interaction with sample or specimen. At
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`para [0075] Cohen et al. teach an advantage to providing freeze—dried material in an assay device
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`is that the device need not be removed from a reader, that no extra step is necessary solely for the
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`purpose of introducing assay reagent or bioactive material. Furthermore, that another advantage
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`is that by using freeze—dried material, refrigeration and other preservation is not always needed,
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`making devices amenable to remote or resource—deprived locations or other places where
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`preservation would be difficult or impossible. At para [0127] for example, Cohen et al. teach
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`antibody may be a freeze—dried reagent (see also paras [0076]—[0077], regarding antibody as the
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`freeze dried assay reagent/bioactive agent).
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`Alternatively to Cohen et al., Tung et al. teach a multifaceted invention which in one
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`aspect is related to the use of antibody compositions immobilized to an solid support/device for
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`the purposes of diagnostic/prognostic assay of an antigenic agent (see e. g. abstract, inventions
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`including a method for detection and a diagnostic tool, a test region or zone; see also e.g. paras
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`[0002], [0005], [0010], [0013], [0023], [0101]—[0102]). Specifically Tung et al. teach
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`immobilization of antibodies to supports (e. g. paras [0109]), that antibodies can be immobilized
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`upon solid supports by a variety of methods and reagents known to the art such to achieve either
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`irreversible, reversible, direct or indirect immobilization of antibody reagent (also see e. g. paras
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`[0157], [0217], [0234]—[0235], [0238], [0240]). Also, at para [0029], Tung et al. define the term
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`“immobilized” (para [0029]) as referring to a moiety that is irreversibly, reversibly, directly or
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`indirectly immobilized to a substrate, “reversibly” (see para [0031]) defined as via non—covalent
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`linking. Therefore, the teachings of Tung et al. are suggestive that such methods for
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`immobilization of antibody are well known to the assay art.
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`Furthermore, it is noted that the instant specification indicates the capturing bodies of the
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`instantly claimed invention are immobilized to the substrate by physical adsorption and not by
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`covalent chemical adsorptions, the instant specification indicating that antibodies immobilized
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`by physical adsorption are therefore apt to desorb from the substrate upon addition of specimen
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`as compared to chemical adsorption methods (i.e. covalent methods). As a result, one of
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`ordinarily skill in the art would appreciate that although Tung et al. does not explicitly recite that
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`reversibly binding antibody by non—covalent means results in some of the antibody coming
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`desorbed from the substrate surface, reversible immobilization (i.e. non—covalent immobilization)
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`would necessarily also lead to some of the immobilized antibody becoming desorbed from the
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`substrate surface as instantly claimed.
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`As such, although Song et al. is silent with respect to whether or not the antibodies are
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`desorbed from the hollow cavity upon addition of sample, it would have been primafacie
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`obvious to one of ordinary skill in the art, at the time of the invention, to provide antibody
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`reagent in freeze—dried form, as taught by Cohen et al., for the surface plasmon device as taught
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`by the Song et al., because Cohen et al. taught that by freeze drying reagent (said reagent thereby
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`being mobilizable upon addition of sample or specimen) one is able to supply the reagent as part
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`of the device, without the need for refrigeration or preservation of reagent, thereby eliminating a
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`step of reagent addition at the time of assay, and further making the device amenable to remove
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`locations or locations where preservation may not be an option. The ordinarily skilled artisan
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`would appreciate that by freeze drying capture bodies to said device as part of the device one is
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`making the device more versatile for the reasons as immediately provided. The ordinarily skilled
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`artisan would reasonably expect success in doing so because Cohen et al. teach the ability to
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`freeze—dry capture bodies (i.e. antibodies) and further because like a surface plasmon sensor as
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`described, the device of Cohen et al. teach fluidic chambers/channels containing said pre—loaded
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`reagent. One would be expected to similarly be able to freeze—dry reagent into a hollow cavity of
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`a plasmon sensor.
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`Alternatively to the preceding analysis, considering that Song et al. is silent with respect
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`to whether or not the antibodies are desorbed from the hollow cavity upon addition of sample, it
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`would have also been primafacie obvious to one of ordinary skill in the art, at the time of the
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`invention, to immobilize antibody to substrate via known methods in the art, including non—
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`covalent, reversible immobilization, as taught by Tung et al., when immobilizing antibody to the
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`surface plasmon device as taught by the Song et al., because Tung et al. taught that such methods
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`for antibody immobilization are well known in the art and used to immobilize antibody to solid
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`support.
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`The ordinarily skilled artisan would appreciate that it is considered obvious to apply a
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`known technique, such as reversible immobilization of antibody, for its known purpose, to
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`immobilize antibody to substrate. As such one would be performing a technique for its known
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`purpose, i.e. to predictably immobilize antibody. The ordinarily skilled artisan would reasonably
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`expect success in doing so because the teachings of Tung et al. teach reversible, non—covalent
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`linking achieves immobilization of antibody to a surface. Furthermore, as discussed in detail
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`above, the invention as described by the combination of Song et al. in view of Tung et al. would
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`similarly be expected to result in some antibody desorption since the invention described by the
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`art teaches a non—covalent immobilization, and the instant specification indicates that non—
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`covalent attachment means are apt to result in such observed desorption.
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`Regarding claim 6, Song et al. teach at para [0059] antibody immobilized on the exposed
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`one side surface of the metal strip 115; thereby Song et al. teach antibodies on one side of the
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`hollow cavity. This statement suggests that antibodies are present on only one metallic surface;
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`thereby indicating an uneven density distribution of the antibodies.
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`Regarding claim 7, Song et al. teach at para [0074], to be analyzed, specimen is injected
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`into the sensor through the channel 117 and comes into close contact with or is adsorbed onto the
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`metal strip; thereby indicating there is necessarily an opening (i.e. a specimen insertion section)
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`in which specimen is injected into the channel containing the capturing bodies. The teaching
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`describes upon insertion, the to—be—analyzed specimen comes in contact with capturing bodies,
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`thereby indicating after insertion (i.e. analyte capturing bodies not disposed in the insertion
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`section/opening, but in the channel).
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`Regarding claim 17, Applicant is directed to the analysis of claim 1 set forth above which
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`addresses the limitations of the instant claim, said limitations were incorporated into amended
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`claim 1.
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`7.
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`Claims 2—3 and 5 are rejected under pre—AIA 35 U.S.C. 103(a) as being unpatentable over
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`Song et al. in view of Cohen et al. (or alternatively Song et al. in view of Tung et al.) as applied
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`to claim 1 above, and further in view of Lyon et al., J. Phys. Chem. B, 103 (1999), p. 5826—5831.
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`Song et al. and Cohen et al., and Song et al. and Tung et al., are each as discussed in
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`detail above, teaching a plasmon sensor device substantially as claimed, but which fail to
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`specifically teach wherein particles are disposed between the first and second metal layers, and
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`that the analyte capturing bodies are chemically adsorbed to the surfaces of the particles; wherein
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`the particles are made of metal; and wherein the sensor further comprises an additive physically
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`adsorbed together with the analyte capturing bodies.
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`Lyon et al. (1999) teach throughout the document and at page 5826, col. 1—2, para [1] the
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`use of an antibody and a gold particle joined together, investigating the influence of the
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`conjugate pair on surface plasmon resonance and its ability to amplify a sensor's biosensing
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`ability. Specifically, Lyon et al. refer to reports that indicate amplified biosensing where large
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`particles are coupled to biomolecules, causing large refractive indeX shifts during bimolecular
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`recognitions events; and also Lyon et al. teach reporting a similar approach wherein colloidal
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`gold was employed as the biocompatible tag for a sandwich immunoassay. Lyon et al. teach
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`there was a greater than 20—fold increase in plasmon angle shift over the observed assay that
`
`employed an unlabeled antibody. The gold particles are disposed on the gold thin film surface,
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`e.g. page 5827, Fig. 1. Furthermore, at page 5826, col. 2, para 1, Lyon et al. teach that colloidal
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`particles pose excellent tags for the determination of extremely low quantities of analyte that are
`
`not routinely observable using traditional assay methods. Also, at page 5826, col. 2 para 1, Lyon
`
`et al. teach that their results demonstrate that by using colloidal gold particles in a sensing
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`device, one provides the potential for significant improvement in the sensitivity and dynamic
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`range of colloidal gold amplified bio—sensing, which is based on the size of the particle.
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`It would have been prima facie obvious to one of ordinary skill in the art, at the time of
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`the invention to have used a conjugate metal antibody pair, disposed on a metallic thin film, as
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`taught by Lyon et al., when constructing the plasmon sensor of Song et al. and Cohen et al. (or
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`alternatively, Song et al. and Tung et al.) because Lyon et al. taught that colloidal gold
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`particle/antibody conjugate pairs perform as excellent signal enhancement of up to a greater than
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`20—fold increase in plasmon angle shift over the observed assay that employed an unlabeled
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`antibody in such sensing devices; and further because Lyon et al. taught that colloidal particles
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`pose excellent tags for the determination of extremely low quantities of analyte that are not
`
`routinely observable using traditional assay methods. Additionally, the ordinarily skilled artisan
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`would have been motivated to perform said modification because Lyon et al. taught that by using
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`colloidal gold particles in a sensing device, one provides the potential for significant
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`improvement in the sensitivity and dynamic range of colloidal gold amplified biosensing. It
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`would therefore have been obvious to improve an apparatus described by the combination of
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`Song et al. and Cohen et al. (or alternatively, Song et al. and Tung et al.) in a similar manner by
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`using the colloidal gold metallic particles of Lyon et al. because said modification would not be
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`expected to change the device so as to alter the way it is used, but rather would be expected to
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`improve the detection capabilities of the device, making it more sensitive.
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`Regarding claim 3, as discussed above, Lyon et al. teaches wherein the particle is made
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`of metal (i.e. gold).
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`Regarding claim 5, as discussed in the analysis above, Lyon et al. addresses wherein the
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`gold colloidal particle is considered to be an additive physically adsorbed together with the
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`analyte capturing body (i.e. antibody). As discussed above, it would be obvious to use colloidal
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`gold to enhance detection.
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`8.
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`Claim 4 is rejected under pre—AIA 35 U.S.C. 103(a) as being unpatentable over Song et
`
`al., in view of Cohen et al. and Lyon et al. (or alternatively, Song et al. in view of Tung et al. and
`
`Lyon et al.) as applied to claim 2 above, and further in view of Yamaguchi et al., Top. Curr.
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`Chem., 288, (2003), p. 237—258.
`
`Song et al., Cohen et al. and Lyon et al. (as well as Song et al., Tung et al. and Lyon et
`
`al.) are each as discussed in detail above, teaching a plasmon sensor substantially as claimed, but
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`which fail to specifically teach wherein the particles are dendrimer.
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`Yamaguchi et al. (2003), at page 254, para 2, teach that antibody biosensor technique
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`based on surface plasmon resonance using antibody dendrimer, allows an advantageous
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`amplification of the detection of signals for antigens. At page 254, para 2, Yamaguchi et al. teach
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`that antibody dendrimer produces an increased signal intensity over the signal of just one
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`antibody alone. Additionally at page 240, para 2, Yamaguchi et al. teach that surface plasmon
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`resonance response reflects a change in mass concentration at the detector surface as molecules
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`bind or dissociate and the specific sensing of substrates with low molecular weight is difficult,
`
`therefore functional molecules with high molecular weight (e. g. antibody dendrimers) have a
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`great potential for amplification.
`
`It would have been prima facie obvious to one of ordinary skill in the art, at the time of
`
`the invention, to have used antibody dendrimer (i.e. dendrimer particles), as taught by
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`Yamaguchi et al., to modify the plasmon sensor as taught by the combination of Song et al.,
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`Cohen et al. and Lyon et al. (or alternatively Song et al., Tung et al. and Lyon et al.), to arrive at
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`the claimed invention because Yamaguchi et al. specifically teach that particles made of antibody
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`dendrimer are advantageous for surface plasmon resonance, specifically that antibody dendrimer
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`also allows amplification of detected signal. It would be obvious to amplify signal of an
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`apparatus used for detection, thereby improving the performance of the apparatus. Furthermore,
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`the ordinarily skilled artisan would be motivated to use antibody dendrimer to modify the
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`invention as taught by the prior art, and achieve amplification of signal, because Song et al. teach
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`that it is possible to make the devices of their invention small and light—weight, the ordinarily
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`skilled artisan appreciating that a small device would utilize minimal sample (i.e. low
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`concentrations). It would be therefore obvious to use known methods to amplify the low
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`concentration signal. The ordinarily skilled artisan would reasonably expect success because the
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`choice of particle would only enhance the performance of the sensor, and not change or interfere
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`with its mode of operation.
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`9.
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`Claims 8, 10, 12—14 and 18 are rejected under pre—AIA 35 U.S.C. 103(a) as being
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`unpatentable over Song et al. in view of Kataoka et al. US PG Pub No. 2005/0106570 (IDS
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`entered 05/27/2014).
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`Song et al. is as discussed in detail above teaching a plasmon sensor substantially as
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`claimed (see rejection of claim 1 above for a complete discussion of the teachings of Song et al.),
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`but fails to specifically teach a plurality of particles are disposed between the first metal layer
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`and the second metal layer, wherein a plurality of analyte capturing bodies are adsorbed to the
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`surface of each of the particles, wherein the plurality of particles are adsorbed to at least one of
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`the first metal layer and the second metal layer via at least a respective one of each plurality of
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`analyte capturing bodies.
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`Kataoka specifically teach providing a high sensitivity bioassay sensor system technique
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`that inhibits non—specific adsorption, said system employing polyethylene glycolated coated
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`particles for signal amplification (see e. g. abstract). At para [0002] Kataoka et al. teach it is
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`known that sensors that utilize surface plasmon resonance are sensitive to refractive index
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`changes near their surface. At para[0005] Kataoka et al. teach sensors chips implementing for
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`example colloidal gold, in general, exhibit advantages of achieving large shifts in plasmon
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`angles, broad width plasmon resonance and remarkable increase in reflectivity, that using
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`colloidal gold or gold nanoparticles for amplification or enhancement of surface plasmon
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`resonance is recognized in the art. Kataoka et al. teach at para [0007], the idea of using gold
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`nanoparticles for improving SPR sensitivity, wherein the sensitization is suggested as depending
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`from the distance between the gold particle and the thin gold membrane surface (i.e. the thin
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`metal layer) of the sensor device. (See also para [0060] regarding surface material as metal). As
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`such, Kataoka et al. teach combination of said plasmon sensor device chips with PEG—modified
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`metal particles for improving dispersion stability (see e. g. para [0008]) (see also paras [0009]—
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`[0019]). Kataoka et al. additional teach a method for detection of analyte in a biological fluid
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`(see e. g. para [0023]—[0028]), using said PEG—modified particles in a competitive assay format
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`(see also para [0071] regarding competitive assay format). At para [0029] teaching particle—
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`biosensor chip set can be linked covalently or non—covalently. See for example, Figure 1,
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`demonstrates the particles at the sensor surface, wherein (i) represents the PEG chain inhibiting
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`non—specific adsorption, (ii) represents the ligand molecule, (iii) represent the gold (see also e. g.
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`[0044] regarding the material as gold) particle (see para [0032]). At para [0040] Kataoka et al.
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`teach the use of the invention for bioassay, wherein one is detection one of a biological specific
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`binding pair such as an antigen or antibody.
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`As such, Kataoka et al. is considered to address a plurality of particles disposed at the
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`metal layer of a sensor, and a plurality of analyte capturing bodies (i.e. a member of a biological
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`specific binding pair, e. g. antibody) adsorbed to the surface of each of the plurality of particles,
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`wherein the plurality of particles are each adsorbed to the metal layer via one of each plurality of
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`analyte capturing bodies (see above and as indicated, Figure 1b).
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`It would have been prima facie obvious to one of ordinary skill in the art, at the time of
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`the invention, to have used PEG—modified gold particles adsorbed to a plasmon sensor surface
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`via a biological specific binding partner such as an antibody, as taught by Kataoka et al., for the
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`plasmon sensor device of Song et al., because Kataoka et al. teach said format allows one to
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`perform competitive binding assay to detect analyte in a biological fluid, Kataoka et al. teaching
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`that the PEG—modified particle technique inhibits non—specific adsorption of components in a
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`sample and makes a more sensitive assay by exploiting known use of a gold particle to enhance
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`detection. One of ordinary skill in the art would reasonably expect success modifying the sensor
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`device of Song et al. with the particle technique of Kataoka et al. because like Kataoka et al.
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`Song et al. describes a plasmon sensor device comprising a metal layer, one of ordinary skill in
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`the art would reasonably expect by introducing the particles of Kataoka et al. into the device of
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`Song et al. that one would achieve a more sensitive device achieving the same signal
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`enhancement effect as Kataoka et al.
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`Regarding claim 10, as discussed above, Kataoka et al. teach the use of colloidal gold or
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`gold nanoparticles, thereby addressing wherein the plurality of particles are made of metal.
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`Regarding claim 12, the gold colloidal particle above is considered to be an additive
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`physically adsorbed together with the analyte capturing body (i.e. antibody). As indicated in the
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`analyses above, it would be obvious to use colloidal gold to enhance detection.
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`Regarding claim 13, Song et al. teach at para [0059] antibody immobilized on the
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`exposed one side surface of the metal strip 115; thereby Song et al. teach antibodies on one side
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`of the hollow cavity. This statement suggests that antibodies are present only on one metallic
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`surface, and modifying the method of Song et al. to implement the particles of Kataoka et