DETAILED ACTION
Contents
I. Notice of Pre-AIA or AIA Status 4
II. Priority 4
III. Continued Examination Under 37 CFR 1.114 4
IV. Pertinent Prosecution History 5
V. Claim Status 7
VI. Reissue Requirements 8
VII. Specification Objections 9
VIII. Drawings Objections 10
IX. Claim Objections 11
X. Claim Interpretation 11
A. Lexicographic Definitions 12
B. 35 U.S.C. § 112 6th Paragraph 12
XI. Claim Rejections – 35 U.S.C. § 251 13
A. Original Patent Requirement 13
XII. Claim Rejections – 35 U.S.C. § 103 15
A. Claims 1 and 19 are rejected under 35 U.S.C. 103 as obvious over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Takaoka (U.S. Publication No. 2010/0268091) and Rabito (U.S. Publication No. 2003/0215391). 16
B. Claims 4, 5, 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Takaoka (U.S. Publication No. 2010/0268091) and Rabito (U.S. Publication No. 2003/0215391) as applied to claims 1 and 19 above, and further in view of Ruchti et al. (U.S. Publication No. 2004/027777)(“Ruchti”). 21
C. Claim 1 is rejected under 35 U.S.C. 103 as obvious over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Takaoka (U.S. Publication No. 2010/0268091), Rabito (U.S. Publication No. 2003/0215391) and Stepp et al. (International Publication No. WO 2016/131886 A1)(“Stepp”). 23
D. Claim 7 is rejected under 35 U.S.C. 103 as obvious over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Rabito (U.S. Publication No. 2003/0215391), Takaoka (U.S. Publication No. 2010/0268091), Rajagopalan et al. (U.S. Patent No. 7,674,902)(“ Rajagopalan”) and Dorshow et al., “Noninvasive Fluorescence Detection of Hepatic and Renal Function” (Dorshow”). 26
E. Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Rabito (U.S. Publication No. 2003/0215391), Takaoka (U.S. Publication No. 2010/0268091) and Rajagopalan et al. (U.S. Patent No. 7,674,902)(“ Rajagopalan”) and Dorshow et al., “Noninvasive Fluorescence Detection of Hepatic and Renal Function” (Dorshow”) as applied to claim 7 above, and further in view of Ruchti et al. (U.S. Publication No. 2004/027777)(“Ruchti”). 35
F. Claim 7 is rejected under 35 U.S.C. 103 as obvious over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Rabito (U.S. Publication No. 2003/0215391), Takaoka (U.S. Publication No. 2010/0268091), Rajagopalan et al. (U.S. Patent No. 7,674,902)(“ Rajagopalan”) and Dorshow et al., “Noninvasive Fluorescence Detection of Hepatic and Renal Function” (Dorshow”) and Stepp et al. (International Publication No. WO 2016/131886 A1)(“Stepp”). 37
XIII. Allowable Subject Matter 40
A. Claims 2, 3, 6, 8-12, 14, 15, 18, 22 and 23 40
XIV. Response to Arguments 42
A. Specification Objection(s) 42
B. Drawings Objection(s) 43
C. Claim Objection(s) 43
D. 35 U.S.C. § 112 Rejections 43
(1) 35 U.S.C.§ 112(a)-(b) Rejections 43
E. 35 U.S.C. § 251 Rejections 44
(1) Broadening Claim Issues 44
F. 35 U.S.C. § 103 Rejections 44
XV. Conclusion 45
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Priority
Applicant filed the instant reissue application 18/108,879 (“‘879 Reissue Application”) on 13 February 2023 for U.S. Application No. 15/884,371 (“‘371 Application”), filed 30 January 2018, now U.S. Patent No. 10,194,854 (“‘854 Patent”), issued 05 February 2019, which claims domestic priority to Provisional Application No. 62/452,021 (“‘021 Prov Application”), filed 30 January 2017.
Thus, the Examiner concludes that for examination purposes the instant ‘879 Reissue Application has an effective filing data of 30 January 2017, which is the filing date of the ‘021 Prov Application.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12 May 2026 has been entered.
Pertinent Prosecution History
As set forth supra, Applicant filed the application for the instant ‘879 Reissue Application on 13 February 2023. The Examiner finds that the instant ‘879 Reissue Application included a preliminary amendment (“Feb 2023 Preliminary Amendment”). The Feb 2023 Preliminary Amendment contained: “Remarks;” “Amendments to the Specification” (“Feb 2023 Spec Amendment”); and “Amendments to the Claims” (“Feb 2023 Claim Amendment”) including: amended original claims 1-10, 12, 14 and 15; original claims 11; canceled original claims 13 and 16; and new claims 17-23.
The Office issued a non-Final Office action on 21 August 2025 (“Aug 2025 Non-Final Office Action”). In particular, the Aug 2025 Non-Final Office Action provided rejections for claim 1-12,14-15 and 17-23 under 35 U.S.C. §§ 103, 112 and 251.1
On 20 November 2025, Applicant filed a Response to Non-Final Office Action (“Nov 2025 Response”). The Nov 2025 Response contained: “Remarks,” “Amendments to the Specification” (“Nov 2025 Spec Amendment”); and “Amendments to the Claims” (“Nov 2025 Claim Amendment”) including: twice amended original2 claims 2-4, 8-10, 14 and 15; amended original3 claims 1, 5-7, 11, 12; original and canceled claims 13 and 16; and amended new4 claims 17-23.
The Office issued a Final Office action on 12 February 2026 (“Feb 2026 Final Office Action”). In particular, the Feb 2026 Final Office Action provided rejections for claim 1-12, 14, 15 and 17-23 (“Rejected Claims”) under 35 U.S.C. §§ 103, 112 and 251.5
On 09 April 2026, Applicant filed a Response after Final Office Action (“April 2026 Response”). The April 2026 Response contained: “Remarks,” “Amendments to the Specification” (“April 2026 Spec Amendment”); “Amendments to the Drawings” (“April 2026 Drawings Amendment”); and “Amendments to the Claims” (“April 2026 Claim Amendment”).
The Office issued an Advisory action on 23 April 2026 (“April 2026 Advisory Action”): not entering the proposed April 2026 Claim Amendment; and asserting that the April 2026 Drawings Amendment is non-compliant.
On 12 May 2026, Applicant filed a second Response after Final Office Action (“May 2026 Applicant Response”). The May 2026 Applicant Response contained: “Remarks,” “Amendments to the Specification” (“May 2026 Spec Amendment”); “Amendments to the Drawings” (“May 2026 Drawings Amendment”);and “Amendments to the Claims” (“May 2026 Claim Amendment”) including: thrice amended original6 claims 2-4, 8, 9 and 15; twice amended original7 claims 1, 5-7, 10, 12 and 14; amended original8 claim 11; original canceled claims 13 and 16; twice amended new9 claims 17-19 and 21-23; and once amended new10 claim 20.
The instant Office Action is a Non-Final Office Action.
Claim Status
The Examiner finds that the claim status in the instant ‘879 Reissue Application is as follows:
Claim(s) 2-4, 8, 9 and 15 (Original and thrice amended)
Claim(s) 1, 5-7, 10, 12 and 14 (Original and twice amended)
Claim(s) 11 (Original and amended)
Claim(s) 13 and 16 (Original and canceled)
Claim(s) 20 (New and amended)
Claim(s) 17-19 and 21-23 (New and twice amended)
Thus, the Examiner concludes that claims 1-12, 14, 15 and 17-23 are pending in the instant ‘879 Reissue Application. Claims 1-12, 14, 15 and 17-23 are examined (“Examined Claims”).
Reissue Requirements
For reissue applications filed before September 16, 2012, all references to 35 U.S.C. 251 and 37 CFR 1.172, 1.175, and 3.73 are to the law and rules in effect on September 15, 2012. Where specifically designated, these are “pre-AIA ” provisions.
For reissue applications filed on or after September 16, 2012, all references to 35 U.S.C. 251 and 37 CFR 1.172, 1.175, and 3.73 are to the current provisions.
Applicant is reminded of the continuing obligation under 37 CFR 1.178(b), to timely apprise the Office of any prior or concurrent proceeding in which the ‘854 Patent is or was involved. These proceedings would include interferences, reissues, reexaminations, post-grant proceedings and litigation.
Applicant is further reminded of the continuing obligation under 37 CFR 1.56, to timely apprise the Office of any information which is mate-rial to patentability of the claims under consideration in this reissue appli-cation.
These obligations rest with each individual associated with the filing and prosecution of this application for reissue. See also MPEP §§ 1404, 1442.01 and 1442.04.
The Examiner notes that Amendment practice for Reissue Applications is NOT the same as for non-provisional applications. See MPEP §§ 1413 and 1453. Reissue application amendments must comply with 37 CFR 1.173, while non-provisional application amendments must comply with 37 CFR 1.121. Particularly,
Manner of making amendments under 37 CFR 1.173:
All markings (underlining and bracketing) are made relative to the original patent text, 37 CFR 1.173(g) (and not relative to the prior amendment).
For amendments to the abstract, specification and claims, the deleted matter must be enclosed in brackets, and the added matter must be underlined. See 37 CFR 1.173(d).
For amendments to the drawings, any changes to a patent drawing must be submitted as a replacement sheet of drawings which shall be an attachment to the amendment document. Any replacement sheet of drawings must be in compliance with § 1.84 and shall include all of the figures appearing on the original version of the sheet, even if only one figure is amended. Amended figures must be identified as "Amended," and any added figure must be identified as "New." In the event that a figure is canceled, the figure must be surrounded by brackets and identified as "Canceled." All changes to the drawing(s) shall be explained, in detail, beginning on a separate sheet accompanying the papers including the amendment to the drawings. See 37 CFR 1.173(d)(3).
The Examiner further notes that all amendments to the instant ‘879 Reissue Application must comply with 37 CFR 1.173(b)-(g).
Specification Objections
The disclosure is objected to because of the following informalities:
In c.49, ll.59-63, the disclosure to “… the fluorescence measurements exhibit a sharp increase 2106 to a peak concentration 2108, followed by a relatively smooth exponential decrease back to background fluorescence levels at the kidneys eliminate the exogenous fluorescence agent from the blood of the patient…” should instead read – … the fluorescence measurements exhibit a sharp increase 2104 to a peak concentration 2106, followed by a relatively smooth exponential decrease 2108 back to background fluorescence levels at the kidneys eliminate the exogenous fluorescence agent from the blood of the patient … – (emphasis added).
In doing so, Applicant should place element number “2104” back into Figure 21.
Appropriate correction is required.
Drawings Objections
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: 100411, 100612, 140413, 210414, etc.
Corrected drawing sheets in compliance with 37 CFR 1.173(b)(3), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.173(b)(1) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure of an amended drawing should be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be surrounded by brackets and identified as "Canceled," and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.173(b)(3). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Appropriate correction is required.
Claim Objections
The May 2026 Claim Amendment does not comply with 37 CFR 1.173(b)(2) and is objected to because Applicant has not provided the correct parenthetical expression (i.e., claim status) for the claims. Specifically, instantly: (1) amended original claims 2-4, 8, 9 and 15 are indicated as “(Twice Amended)” when instead they should be indicated as “(Thrice Amended); (2) amended original claim 11 is indicated as “(Twice Amended)” when instead it should be indicated as “(Amended); and (3) amended new claim 20 is indicated as “(New, Twice Amended)” when instead it should be indicated as “(New, Amended). (See 37 CFR 1.173(b); and MPEP §§ 1453.II, V.D-E).
Appropriate correction is required.
Claim Interpretation
During examination, claims are given the broadest reasonable interpretation consistent with the specification and limitations in the specification are not read into the claims. See MPEP § 2111, MPEP § 2111.01 and In re Yamamoto et al., 222 USPQ 934 (Fed. Cir. 1984). Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01(I). It is further noted it is improper to import claim limitations from the specification, i.e., a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment. See MPEP § 2111.01(II). Therefore, unless one of the exceptions applies below, Examiners will interpret the limitations of the pending and examined claims using the broadest reasonable interpretation.
Lexicographic Definitions
A first exception to the prohibition of reading limitations from the specification into the claims is when the Applicant for patent has provided a lexicographic definition for the term. (See MPEP § 2111.01(IV)). After careful review of the original specification, the prosecution history, and unless expressly noted otherwise by the Examiner, the Examiner finds that he is unable to locate any lexicographic definitions (either express or implied) with reasonable clarity, deliberateness, and precision. Because the Examiner is unable to locate any lexicographic definitions with reasonable clarity, deliberateness, and precision, the Examiner concludes that Applicant is not his/her own lexicographer. (Id.)
35 U.S.C. § 112 6th Paragraph
A second exception to giving words in the claims their ordinary and customary meaning is when a claimed phrase is interpreted in accordance with 35 U.S.C. § 112 6th paragraph. See MPEP § 2181 et seq.
The Examiner finds that because the Examined Claims do not recite “step,” “means” or a claim term used as a substitution for “means” (i.e. a generic placeholder for “means”), the Examined Claims fail Prong (A) as set forth in MPEP §2181. Because the twenty-one (21) Examined Claims fail Prong (A) as set forth in MPEP §2181 I., the Examiner concludes that all Examined Claims do not invoke 35 U.S.C. §112, 6th paragraph. See also Ex parte Miyazaki, 89 USPQ2d 1207, 1215-16 (B.P.A.I. 2008)(precedential).
Claim Rejections – 35 U.S.C. § 251
Original Patent Requirement
Claim 5 is rejected under 35 U.S.C. 251 as being in violation of the original patent requirement.
Section 251 requires that reissue is for “the invention disclosed in the original patent.” In order to satisfy the original patent requirement, “[i]t must appear from the face of the instrument that what is covered by the reissue was intended to have been covered and secured by the original.” U.S. Indus. Chems., Inc. v. Carbide & Carbon Chems. Corp., 315 U.S. 668, 676 (1942). Furthermore, “it is not enough that an invention might have been claimed in the original patent because it was suggested or indicated in the specification.” Id. In other words, the original patent “must clearly and unequivocally disclose the newly claimed invention as a separate invention.” Antares Pharma, Inc. v. Medac Pharma Inc., 771 F.3d 1354, 1362 (Fed. Cir. 2014).
In the instant case, it does not appear from the face of the original patent that Applicant intended to cover a method for: (1) monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties; or (2) determining renal function in a patient without the removing the effects of autofluorescence contribution step specifically including obtaining the IFagent signal through subtracting the IFauto signal from the Flrphotons signal.
The Technical Problem makes clear that the invention is drawn to a method for monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties to remove the effects of leak-through of excitation-level light and removing the effects of autofluorescence from the Flrmeas signal. (‘854 Patent at Abstract).
The Examiner finds the problem is solved by a particular method comprising embodiments in which:
the effect of autofluorescence may be removed by subtracting the IFauto value obtained in Eqn. (32) from the corrected fluorescence signal Flrphotons as expressed in Eqn. (33):
IFagent = Flrphotons − IFauto Eqn. (33)
where IFagent denotes the intrinsic fluorescence specifically representing the emission-wavelength light emitted by the exogenous fluorescent agent.
(‘854 Patent at c.47, ll.54-62). The claims as filed and during prosecution were always drawn to a method comprising the operation of multiple steps including the removing the effects of autofluorescence contribution step specifically including obtaining the IFagent signal through subtracting the IFauto signal from the Flrphotons signal. (Id.; emphasis added; also see original claims 5 and 11 filed 30 January 2018 in the ‘371 Application (“Jan 2018 ‘371 Application Claims”)).
This situation is also somewhat analogous to the recent Federal Circuit decision in Forum US, Inc. v. Flow Valve, LLC, 926 F.3d 1346 (Fed. Cir. 2019). In Forum US, the original patent claims were drawn to a workpiece having a body member and a plurality of arbors (arbors circled):
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Forum US, 926 F.3d at 1348-49. In reissue, patentee broadened the claims to remove the requirement as to arbors. Id. at 1349. The Federal Circuit determined that the new claims did not comply with the original patent requirement of section 251 because the face of the patent did not disclose any arbor-less embodiment, and the abstract, summary of invention, and all disclosed embodiments including arbors. Id. at 1352. The Court concluded that the specification did not clearly and unequivocally disclose an embodiment without arbors, thus the original patent requirement was violated by broadening the claims to no longer require arbors. Id. Similarly, the patent here does not clearly and unequivocally disclose any embodiment that includes a method comprising performing the step of:
claim 5, including:
wherein removing the effects of autofluorescence contribution further comprises subtracting the IFauto from the Flrphotons
(May 2026 Claim Amendment. at claim 5 without obtaining the IFagent signal through subtracting the IFauto signal from the Flrphotons signal.
Claim Rejections – 35 U.S.C. § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1 and 19 are rejected under 35 U.S.C. 103 as obvious over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Takaoka (U.S. Publication No. 2010/0268091) and Rabito (U.S. Publication No. 2003/0215391).
With respect to the limitations of claim 1, and
[1] [a] method of monitoring a time-varying fluorescence emitted from [a] an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties, the method comprising:
In this regard, the Examiner finds that Zand discloses a method of determining the characteristics of tissue organ (e.g., an organ) utilizing an exogenous fluorescent indicator and monitoring the fluorescence from the tissue of a patient. (Zand at Abstract; ¶¶ 0002, 0012, 0054-0055, 0079, 0082-0087, 0095, 0109; see Figures 1, 5a, 8a, 8b, 9, 10a-10c, 11d).
providing a measurement data set comprising a plurality of measurement data entries, each measurement data entry comprising at least two measurements obtained at one data acquisition time from a patient before and after administration of the exogenous fluorescent agent, the at least two measurements comprising a Flrmeas (fluorescence emission) signal detected at a third region adjacent to the diffuse reflecting medium by a filtered light detector during illumination of the diffuse reflecting medium by an excitatory-wavelength light from a first region, and at least one DR (diffuse reflection) signal selected from:
a DRexmeas signal detected at a second region adjacent to the diffuse reflecting medium by an unfiltered light detector during illumination of the diffuse reflecting medium by excitatory-wavelength light from the first region adjacent to the diffuse reflecting medium;
a DRem signal detected at the second region by the unfiltered light detector during illumination of the diffuse reflecting medium by an emission-wavelength light from the first region; and
a DRem,filtered signal detected at the third region by the filtered light detector during illumination of the diffuse reflecting medium by emission-wavelength light from the first region;
In this regard, the Examiner finds that Zand discloses an excitation light providing an illumination that irradiates an exogenous fluorescent indicator within the tissue of a patient. (Zand at ¶¶ 0082-0087). The Examiner finds that Zand discloses sensors providing data (i.e.. signals) obtained by measuring the intensity of the fluoresced response of various regions within the patient’s tissue before and after the introduction of the exogenous fluorescent indicator to the patient. (Id.)
Zand discloses the limitations, as previously set forth, except for specifically calling for each data point entry having two measurements obtained via sensors in which one data point is from a filtered light detector sensor and the other is from an unfiltered light detector sensor.
However, providing data point entries having two measurements each obtained via sensors in which one data point is from a filtered light detector sensor and the other is from an unfiltered light detector sensor is known in the art. The Examiner finds that Takaoka, for example, teaches a fluorescence imaging apparatus comprising a filtered light detector sensor and an unfiltered light detector sensor providing data point entries with two measurements at each data point. (Takaoka at Abstract; ¶¶ 0003, 0012, 0033, 0046).
The Examiner finds that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate providing data point entries having two measurements each obtained via sensors in which one data point is from a filtered light detector sensor and the other is from an unfiltered light detector sensor as described in Takaoka, in the method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium of Zand.
A person of ordinary skill in the art would be motivated to incorporate providing data point entries having two measurements each obtained via sensors in which one data point is from a filtered light detector sensor and the other is from an unfiltered light detector sensor, since it provides a mechanism to block excitation light and provide image data comprising data points in which candidate sites shine more brightly from the fluorescence. (Id. at ¶ 0046). In other words, such a modification would optimize the detection of characteristics excited by fluorescent agents within a patient, thereby inherently increasing the operational efficiency. (Id.)
identifying a post-agent-administration portion of the measurement data set
Zand and Takaoka discloses the limitations, as previously set forth, except for specifically calling for identifying a post-agent-administration portion of the measurement data set.
However, identifying a post-agent-administration portion of the measurement data set is known in the art. The Examiner finds that Rabito, for example, teaches the utilization of fluorescent agents for real-time measurement of organ function in which the identification agent of the measurement data is performed at a post-agent-administration portion of the measurement data set. (Rabito at ¶ 0046).
The Examiner finds that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate identifying a post-agent-administration portion of the measurement data set as described in Rabito, in the method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium of Zand and Takaoka.
A person of ordinary skill in the art would be motivated to incorporate identifying a post-agent-administration portion of the measurement data set, since it provides a mechanism to allow for background fluorescence to sufficient decay and prevent quenching. (Id.) In other words, such a modification would optimize the detection of characteristics excited by fluorescent agents within a patient, thereby inherently increasing the operational efficiency. (Id.)
transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium, wherein the transforming comprises at least one of removing the effects of leak-through of excitation-level light into the Flrmeas signal and removing the effects of autofluorescence contribution from the Flrmeas signal; and
In this regard, Zand discloses measuring fluorescence before and after the introduction of a fluorescence indicator. (Zand at Abstract; ¶¶ 0082-0087; see Figure 8a). In addition, the Examiner finds that Zand teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “baseline intensity” and subtracting this “baseline intensity” from the values measured at the other times. (Id. at ¶ 0085-0086). Since the “baseline intensity” is only based upon the tissue and the fluorophores found in the tissue prior to introduction of the fluorescence indicator, the Examiner finds that this “baseline intensity” would be equivalent to the effects of autofluorescence contribution from the Flrmeas signal.”
monitoring the IFagent signal for each measurement data entry within the post-agent-administration portion of the measurement data set.
In this regard, Zand discloses the corrected measurements being recorded and further processed. (Id. at ¶ 0086; also see ¶¶ 0106-0109 and Figure 14 for integrated system).
With respect to the limitations of claim 19, and
[19] wherein removing the effects of autofluorescence comprises determining IFbkrnd, representing intrinsic fluorescence data obtained before administration of the exogenous fluorescent agent, by combining the IFbkrnd signal with at least of one of the DRexmeas, a DRem signal and DRem,filtered signals wherein the signals are obtained before administration of the exogenous fluorescent agent
In this regard, the Examiner finds that Zand teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “baseline intensity” and subtracting this “baseline intensity” from the values measured at the other times. (Id. at ¶ 0085-0086). The Examiner finds that the this “baseline intensity” would inherently include the Flrmeas signal and at least one of the DRexmeas, a DRem signal and DRem,filtered signals.
Claims 4, 5, 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Takaoka (U.S. Publication No. 2010/0268091) and Rabito (U.S. Publication No. 2003/0215391) as applied to claims 1 and 19 above, and further in view of Ruchti et al. (U.S. Publication No. 2004/027777)(“Ruchti”).
With respect to the limitations of claims 4 and 20, and
[4] wherein the removing the effects of autofluorescence contribution to comprises determining IFauto, representing intrinsic autofluorescence emitted by endogenous chromophores within the diffuse reflecting medium, by determining a value of the Flrphotons signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent, the value selected from the group consisting of mean and median
[20] wherein the removing the effects of autofluorescence contribution to comprises determining IFauto, representing intrinsic autofluorescence contribution emitted by endogenous chromophores within the diffuse reflecting medium, by determining a value of the IFbkrnd signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent, the value selected from the group consisting of mean and median
As set forth above, Zand teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “baseline intensity” and subtracting this “baseline intensity” from the values measured at the other times. (Id. at ¶ 0085-0086). (See § XII.A.(1).(c), supra).
Zand, Takaoka and Rabito discloses the limitations, as previously set forth, except for specifically calling for the removing the effects of autofluorescence to comprise determining IFauto by determining a value of the Flr/ IFbkrnd signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent, the value selected from the group consisting of mean and median.
However, removing the effects of background noise comprising determining a value representation of a tissue measurement at some point time prior to collection data and that value being selected as an estimate of the mean of several values is known in the art. Ruchti, for example, teaches a system and method of measuring analytic properties of tissue and to remove the noise induced by the tissue by calculating a value representative of tissue measurement as some point in time prior to the collection of data which can be determined either from a single tissue measurement or from the mean of several tissue measurements. (Ruchti at Abstract; ¶¶ 0112-0115).
Therefore, because these two determinations of a tissue measurement noise factor were art-recognized equivalents at the time the invention was made, a person of ordinary skill in the art would have found it obvious to substitute determining a value from a single measurement of the Flr/ IFbkrnd signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent in Zand, Takaoka and Rabito with determining a mean value from a plurality of measurements of the Flr/ IFbkrnd signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent.
Moreover, the Examiner finds that simple substitution of one known element for another would obtain predictable results. That is, the substitution of one known element determining a mean value from a plurality of measurements of the Flr/ IFbkrnd signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent) for another (determining a value from a single measurement of the Flr/ IFbkrnd signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent) would have been obvious to one of ordinary skill in the art at the time of the invention since the substitution of determining a mean value from a plurality of measurements for determining a value from a single measurement would have yielded predictable results, namely, removing noise that is provided by tissue.
With respect to the limitations of claims 5 and 21, and
[5] wherein the removing the effects of autofluorescence contribution further comprises subtracting the IFauto from the Flrphotons signal.
[21] wherein the removing the effects of autofluorescence contribution further comprises subtracting the IFauto signal from the Flrphotons signal to obtain the IFagent signal.
As set forth above, Zand teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “baseline intensity” and subtracting this “baseline intensity” from the values measured at the other times. (Id. at ¶ 0085-0086). (See § XII.A.(1).(c), supra).
Claim 1 is rejected under 35 U.S.C. 103 as obvious over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Takaoka (U.S. Publication No. 2010/0268091), Rabito (U.S. Publication No. 2003/0215391) and Stepp et al. (International Publication No. WO 2016/131886 A1)(“Stepp”).
With respect to the limitations of claim 1, The Examiner finds that Zand, Takaoka and Rabito teaches and/or renders obvious all the claim requirements of claim 1. (See § XII.A.(1), supra).
However, to the degree a reviewing body finds that it is not inherent that Zand teaches “transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium, wherein the transforming comprises at least one of the effects of autofluorescence contribution from the Flrmeas signal,” the following alternative to this feature is provided as set forth below:
As set forth above, Zand teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “baseline intensity” and subtracting this “baseline intensity” from the values measured at the other times. (Id. at ¶ 0085-0086).
Zand, Takaoka and Rabito discloses the limitations, as previously set forth, except for specifically calling for transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium, wherein the transforming comprises removing at least one of the effects of leak-through of excitation-level light into the Flrmeas signal and removing the effects of autofluorescence contribution from the Flrmeas signal.
However, transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to a corrected fluorescent signal, wherein the transforming comprises removing at least one of the effects of leak-through of excitation-level light into the Flrmeas signal and removing the effects of autofluorescence contribution from the Flrmeas signal. The Examiner finds that Stepp, for example, teaches transforming the measured intensity of the fluorescent light emitted from a patient utilizing a determined correction factor which is based upon the autofluorescence emitted by tissue to determine the quantitative measure of the fluorescent analyte being utilized. (p.3, ll.6-13, 18-20; p.3, l.24 – p.4, l.4; p.4, ll.18-22; p.6, l.32 – p.7, l.7; p.12, l.5 – p.13, l.18; p16, l.20 – p.19, l.12; see claims 20, 24, 26).
The Examiner finds that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium, wherein the transforming comprises removing the effects of autofluorescence contribution from the Flrmeas signal, as described in Stepp in the method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium of Zand. Takaoka and Rabito.
A person of ordinary skill in the art would be motivated to incorporate transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium, wherein the transforming comprises removing the effects of autofluorescence contribution from the Flrmeas signal, since it provides a mechanism to remove the effects of fluorophores that are found in the tissue and provide a good location to take measurements. (Id. at p.3, ll.27-28; p.16, ll.20-24; p.18, ll.1-8). In other words, such a modification would optimize the detection of characteristics excited by fluorescent agents within a patient, thereby inherently increasing the operational efficiency. (Id.)
Claim 7 is rejected under 35 U.S.C. 103 as obvious over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Rabito (U.S. Publication No. 2003/0215391), Takaoka (U.S. Publication No. 2010/0268091), Rajagopalan et al. (U.S. Patent No. 7,674,902)(“ Rajagopalan”) and Dorshow et al., “Noninvasive Fluorescence Detection of Hepatic and Renal Function” (Dorshow”).
With respect to the limitations of claim 7, and
[7] [a] method of determining renal function in a patient the method comprising:
In this regard, the Examiner finds that Zand discloses a method of determining the characteristics of tissue organ (e.g., an organ) utilizing an exogenous fluorescent indicator and monitoring the fluorescence from the tissue of a patient. (Zand at Abstract; ¶¶ 0002, 0012, 0054-0055, 0079, 0082-0087, 0095, 0109; see Figures 1, 5a, 8a, 8b, 9, 10a-10c, 11d).
Zand discloses the limitations, as previously set forth, except for specifically calling for the method of determining the characteristics of tissue organ (e.g., an organ) utilizing an exogenous fluorescent indicator to determine renal function.
However, a method of determining the characteristics of tissue organ (e.g., an organ) utilizing an exogenous fluorescent indicator to determine renal function is known in the art. The Examiner finds that Rabito, for example, teaches a system and method utilizing an exogenous fluorescent indicator to determine renal function in a patient. (¶¶ 0046-0049).
The Examiner finds that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the method of determining the characteristics of tissue organ (e.g., an organ) to utilize an exogenous fluorescent indicator to determine renal function as described in Rabito, in the method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium of Zand.
A person of ordinary skill in the art would be motivated to incorporate utilizing an exogenous fluorescent indicator to determine renal function, since it provides a mechanism for real-time monitoring of renal function. (Id. at ¶ 0049). In other words, such a modification would optimize the detection of characteristics excited by fluorescent agents within a patient, thereby inherently increasing the operational efficiency. (Id.)
providing a measurement data set comprising a plurality of measurement data entries, each measurement data entry comprising at least two measurements obtained at one data acquisition time from a patient before and after administration of the exogenous fluorescent agent, the at least two measurements comprising a Flrmeas (fluorescence emission) signal detected at a third region adjacent to a diffuse reflecting medium by a filtered light detector during illumination of the diffuse reflecting medium by an excitatory-wavelength light from a first region, and at least one DR (diffuse reflection) signal selected from:
a DRexmeas signal detected at a second region adjacent to the diffuse reflecting medium by an unfiltered light detector during illumination of the diffuse reflecting medium by excitatory-wavelength light from the first region adjacent to the diffuse reflecting medium;
a DRem signal detected at the second region by the unfiltered light detector during illumination of the diffuse reflecting medium by an emission-wavelength light from the first region; and
a DRem,filtered signal detected at the third region by the filtered light detector during illumination of the diffuse reflecting medium by emission-wavelength light from the first region;
In this regard, the Examiner finds that Zand discloses an excitation light providing an illumination that irradiates an exogenous fluorescent indicator within the tissue of a patient. (Zand at ¶¶ 0082-0087). The Examiner finds that Zand discloses sensors providing data (i.e.. signals) obtained by measuring the intensity of the fluoresced response of various regions within the patient’s tissue before and after the introduction of the exogenous fluorescent indicator to the patient. (Id.)
Zand and Rabito discloses the limitations, as previously set forth, except for specifically calling for each data point entry having two measurements obtained via sensors in which one data point is from a filtered light detector sensor and the other is from an unfiltered light detector sensor.
However, providing data point entries having two measurements each obtained via sensors in which one data point is from a filtered light detector sensor and the other is from an unfiltered light detector sensor is known in the art. The Examiner finds that Takaoka, for example, teaches a fluorescence imaging apparatus comprising a filtered light detector sensor and an unfiltered light detector sensor providing data point entries with two measurements at each data point. (Takaoka at Abstract; ¶¶ 0003, 0012, 0033, 0046).
The Examiner finds that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate providing data point entries having two measurements each obtained via sensors in which one data point is from a filtered light detector sensor and the other is from an unfiltered light detector sensor as described in Takaoka, in the method of determing renal function of a patient of Zand and Rabito.
A person of ordinary skill in the art would be motivated to incorporate providing data point entries having two measurements each obtained via sensors in which one data point is from a filtered light detector sensor and the other is from an unfiltered light detector sensor, since it provides a mechanism to block excitation light and provide image data comprising data points in which candidate sites shine more brightly from the fluorescence. (Id. at ¶ 0046). In other words, such a modification would optimize the detection of characteristics excited by fluorescent agents within a patient, thereby inherently increasing the operational efficiency. (Id.)
identifying a post-agent-administration portion of the measurement data set
Zand, Rabito and Takaoka discloses the limitations, as previously set forth, except for specifically calling for identifying a post-agent-administration portion of the measurement data set.
However, identifying a post-agent-administration portion of the measurement data set is known in the art. The Examiner finds that Rabito, for example, teaches the utilization of fluorescent agents for real-time measurement of organ function in which the identification agent of the measurement data is performed at a post-agent-administration portion of the measurement data set. (Rabito at ¶ 0046).
The Examiner finds that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate identifying a post-agent-administration portion of the measurement data set as described in Rabito, in the method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium of Zand, Rabito and Takaoka.
A person of ordinary skill in the art would be motivated to incorporate identifying a post-agent-administration portion of the measurement data set, since it provides a mechanism to allow for background fluorescence to sufficient decay and prevent quenching. (Id.) In other words, such a modification would optimize the detection of characteristics excited by fluorescent agents within a patient, thereby inherently increasing the operational efficiency. (Id.)
transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium, wherein the transforming comprises at least one of removing the effects of leak-through of excitation-level light into the Flrmeas signal and removing the effects of autofluorescence contribution from the Flrmeas signal; and
In this regard, Zand discloses measuring fluorescence before and after the introduction of a fluorescence indicator. (Zand at Abstract; ¶¶ 0082-0087; see Figure 8a). In addition, the Examiner finds that Zand teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “baseline intensity” and subtracting this “baseline intensity” from the values measured at the other times. (Id. at ¶ 0085-0086). Since the “baseline intensity” is only based upon the tissue and the fluorophores found in the tissue prior to introduction of the fluorescence indicator, the Examiner finds that this “baseline intensity” would be equivalent to the effects of autofluorescence contribution from the Flrmeas signal.”
identifying a post-equilibration portion of the measurement data set;
In this regard, Zand, Takaoka and Rabito teaches and/or renders obvious identifying a post-equilibration portion of the measurement data set. As set forth above, Rabito teaches the utilization of fluorescent agents for real-time measurement of organ function in which the identification agent of the measurement data is performed at a post-equilibrium portion of the measurement data set. (Rabito at ¶ 0046).
The Examiner finds that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate identifying a post-equilibrium portion of the measurement data set as described in Rabito, in the method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium of Zand and Takaoka.
A person of ordinary skill in the art would be motivated to incorporate identifying a post-equilibrium portion of the measurement data set, since it provides a mechanism to allow for background fluorescence to sufficient decay and prevent quenching. (Id.) In other words, such a modification would optimize the detection of characteristics excited by fluorescent agents within a patient, thereby inherently increasing the operational efficiency. (Id.)
transforming the IFagent signals corresponding to the post-equilibration portion of the measurement data set to a rate of change of the IFagent signals; and
determining the renal function in the patient based on the rate of change of the IFagent signals
In this regard, the Zand discloses a method of determining the characteristics of tissue organ (e.g., an organ) utilizing an exogenous fluorescent indicator and monitoring the fluorescence from the tissue of a patient. (Zand at Abstract; ¶¶ 0002, 0012, 0054-0055, 0079, 0082-0087, 0095, 0109; see Figures 1, 5a, 8a, 8b, 9, 10a-10c, 11d). In addition, Rabito teaches a system and method utilizing an exogenous fluorescent indicator to determine renal function in a patient. (¶¶ 0046-0049).
Zand, Takaoka and Rabito discloses the limitations, as previously set forth, except for specifically calling for transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals.
However, transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals is known in the art. The Examiner finds that Rajagopalan, for example, teaches the utilization of non-invasive probes utilizing the optical florescence agent tracer methods to characterize physiological functions based upon the clearance profiles and rates of the fluorescent agents from the body fluids. (Rajagopalan at c.9, ll.47-60). Moreover, with respect to such functionality, Rajagopalan references Dorshow to teach the slower rate of change of the “in vivo fluorescence time” correlating to impaired functionality of the organ in question. (Dorshow at § 3.1.3).
The Examiner finds that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals as described in Rajagopalan and Dorshow, in the method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium of Zand, Rabito and Takaoka.
A person of ordinary skill in the art would be motivated to incorporate transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals, since it provides a mechanism to actively determine organ functionality with optical florescence agent tracer methods alone. (Rajagopalan at c.9, ll.50-60; and Dorshow at 3.1.3). In other words, such a modification would optimize the utilization of detection characteristics excited by fluorescent agents within a patient, thereby inherently increasing the operational efficiency.
Furthermore, this combination of references also satisfies at least rationale C identified by the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385, 1395-97 (2007): "Use of known technique to improve similar devices (methods, or products) in the same way." (See MPEP 2143.) The elements of the Graham factual inquiry for supporting a finding of obviousness based on this rationale are provided below:
(1) A finding that the prior art (Zand, Rabito and Takaoka) contained a “base” device (a system and method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium) upon which the claimed invention can be seen as an “improvement” for including “transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals” in order to optimize the utilization of detection characteristics excited by fluorescent agents within a patient.
(2) A finding that the prior art (Rajagopalan, in light of Dorshow) contained a "comparable" device (a system and method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium) that has been improved in the same way as the claimed invention, i.e. the Rajagopalan, in light of Dorshow, system and method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium utilizing “transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals” in order to actively determine organ functionality with optical florescence agent tracer methods alone.
(3) A finding that one of ordinary skill in the art could have applied the known “improvement” technique in the same way to the “base” device (the Zand, Rabito and Takaoka system and method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium) and the results would have been predictable to one of ordinary skill in the art. Here, because Zand, Rabito and Takaoka indicates that system and method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium can utilize an exogenous fluorescent indicator and monitor the fluorescence from the tissue of a patient to determine the renal functionality of a patient and Rajagopalan, in light of Dorshow, teaches a manner for improving this, the results would be predictable. In other words, the Rajagopalan, in light of Dorshow, successful implementation or providing “transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals” proves that the implementation is both successful and entirely predictable. In Zand, Rabito and Takaoka, the system and method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium modified according to Rajagopalan, in light of Dorshow, would be capable of incorporating “transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals” to carry out the function of actively determine organ functionality with optical florescence agent tracer methods alone, as evidenced by the success in the optimized system and method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium.
In that regard, the Examiner asserts the use of known technique to improve similar devices in the same way is obvious to one of ordinary skill in the art. That is, the manner of enhancing a particular device (actively determining organ functionality with optical florescence agent tracer methods alone including “transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals”) was made part of the ordinary capabilities of one skilled in the art based upon the teaching of such improvement in Rajagopalan, in light of Dorshow. Accordingly, one of ordinary skill in the art would have been capable of applying this known “improvement” technique in the same manner to the prior art system and method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium of Zand, Rabito and Takaoka and the results would have been predictable to one of ordinary skill in the art, namely, one skilled in the art would have readily recognized that actively determining organ functionality with optical florescence agent tracer methods alone including “transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals”)” in Zand, Rabito and Takaoka would positively provide a means to carry out, in addition to simply utilizing an exogenous fluorescent indicator and monitoring the fluorescence from the tissue of a patient to determine the renal functionality of a patient, a new function of actively determine organ functionality with optical florescence agent tracer methods alone, without fluidic analysis, since such functionality is taught to be highly desirable by Rajagopalan, in light of Dorshow, as set forth above.
Thus, the rationale to support a conclusion that the claim would have been obvious is that a method of enhancing a particular class of devices (methods, or products) has been made part of the ordinary capabilities of one skilled in the art based upon the teaching of such improvement in other situations. One of ordinary skill in the art would have been capable of applying this known method of enhancement to a “base” device (method, or product) in the prior art and the results would have been predictable to one of ordinary skill in the art. The Supreme Court in KSR noted that if the actual application of the technique would have been beyond the skill of one of ordinary skill in the art, then using the technique would not have been obvious. KSR, 550 U.S. at 398, 82 USPQ2d at 1396.
Similarly, the Examiner asserts that applying a known technique to a known device ready for improvement would yield predictable results. That is, it would have been recognized by one of ordinary skill in the art that applying the known technique taught by Rajagopalan, in light of Dorshow, to the system and method of Zand, Takaoka and Rabito would have yielded predicable results and resulted in an improved system, namely, providing the system and method for transforming the IFagent signals to a rate of change of the IFagent signals; and determining the renal function in the patient based on the rate of change of the IFagent signals, in Zand, Takaoka and Rabito to deliver a mechanism for actively determining organ functionality with optical florescence agent tracer methods alone.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Rabito (U.S. Publication No. 2003/0215391), Takaoka (U.S. Publication No. 2010/0268091) and Rajagopalan et al. (U.S. Patent No. 7,674,902)(“ Rajagopalan”) and Dorshow et al., “Noninvasive Fluorescence Detection of Hepatic and Renal Function” (Dorshow”) as applied to claim 7 above, and further in view of Ruchti et al. (U.S. Publication No. 2004/027777)(“Ruchti”).
With respect to the limitations of claim 17, and
[17] wherein the removing the effects of autofluorescence contribution to comprises determining IFauto, representing intrinsic autofluorescence contribution emitted by endogenous chromophores within the diffuse reflecting medium, by determining a value of the Flrphotons signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent, the value selected from the group consisting of mean and median
As set forth above, Zand teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “baseline intensity” and subtracting this “baseline intensity” from the values measured at the other times. (See § XII.D.(1).(c), supra).
Zand, Rabito, Takaoka, Rajagopalan and Dorshow discloses the limitations, as previously set forth, except for specifically calling for the removing the effects of autofluorescence to comprises determining IFauto by determining a value of the Flrphotons signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent, the value selected from the group consisting of mean and median.
However, removing the effects of background noise comprising determining a value representation of a tissue measurement at some point time prior to collection data and that value being selected as an estimate of the mean of several values is known in the art. Ruchti, for example, teaches a system and method of measuring analytic properties of tissue and to remove the noise induced by the tissue by calculating a value representative of tissue measurement as some point in time prior to the collection of data which can be determined either from a single tissue measurement or from the mean of several tissue measurements. (Ruchti at Abstract; ¶¶ 0112-0115).
Therefore, because these two determinations of a tissue measurement noise factor were art-recognized equivalents at the time the invention was made, a person of ordinary skill in the art would have found it obvious to substitute determining a value from a single measurement of the Flrphotons signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent in Zand, Rabito, Takaoka, Rajagopalan and Dorshow with determining a mean value from a plurality of measurements of the Flrphotons signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent.
Moreover, the Examiner finds that simple substitution of one known element for another would obtain predictable results. That is, the substitution of one known element determining a mean value from a plurality of measurements of the Flrphotons signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent) for another (determining a value from a single measurement of the Flrphotons signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent) would have been obvious to one of ordinary skill in the art at the time of the invention since the substitution of determining a mean value from a plurality of measurements for determining a value from a single measurement would have yielded predictable results, namely, driving the NAND wafers in the device while saving space and cost in the device.
Claim 7 is rejected under 35 U.S.C. 103 as obvious over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”) in view of Rabito (U.S. Publication No. 2003/0215391), Takaoka (U.S. Publication No. 2010/0268091), Rajagopalan et al. (U.S. Patent No. 7,674,902)(“ Rajagopalan”) and Dorshow et al., “Noninvasive Fluorescence Detection of Hepatic and Renal Function” (Dorshow”) and Stepp et al. (International Publication No. WO 2016/131886 A1)(“Stepp”).
With respect to the limitations of claim 7, The Examiner finds that Zand, Rabito, Takaoka, Rajagopalan and Dorshow teaches and/or renders obvious all the claim requirements of claim 7. (See § XIII.D.(1), supra).
However, to the degree a reviewing body finds that it is not inherent that Zand teaches “transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium, wherein the transforming comprises at least one of the effects of autofluorescence contribution from the Flrmeas signal,” the following alternative to this feature is provided as set forth below:
As set forth above, Zand teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “baseline intensity” and subtracting this “baseline intensity” from the values measured at the other times. (Id. at ¶ 0085-0086).
Zand, Rabito, Takaoka, Rajagopalan and Dorshow discloses the limitations, as previously set forth, except for specifically calling for transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium, wherein the transforming comprises removing at least one of the effects of leak-through of excitation-level light into the Flrmeas signal and removing the effects of autofluorescence contribution from the Flrmeas signal.
However, transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to a corrected fluorescent signal, wherein the transforming comprises removing at least one of the effects of leak-through of excitation-level light into the Flrmeas signal and removing the effects of autofluorescence contribution from the Flrmeas signal. The Examiner finds that Stepp, for example, teaches transforming the measured intensity of the fluorescent light emitted from a patient utilizing a determined correction factor which is based upon the autofluorescence emitted by tissue to determine the quantitative measure of the fluorescent analyte being utilized. (p.3, ll.6-13, 18-20; p.3, l.24 – p.4, l.4; p.4, ll.18-22; p.6, l.32 – p.7, l.7; p.12, l.5 – p.13, l.18; p16, l.20 – p.19, l.12; see claims 20, 24, 26).
The Examiner finds that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium, wherein the transforming comprises removing the effects of autofluorescence contribution from the Flrmeas signal, as described in Stepp in the method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent of the diffuse reflecting medium of Zand, Rabito, Takaoka, Rajagopalan and Dorshow.
A person of ordinary skill in the art would be motivated to incorporate transforming the Flrmeas signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium, wherein the transforming comprises removing the effects of autofluorescence contribution from the Flrmeas signal, since it provides a mechanism to remove the effects of fluorophores that are found in the tissue and provide a good location to take measurements. (Id. at p.3, ll.27-28; p.16, ll.20-24; p.18, ll.1-8). In other words, such a modification would optimize the detection of characteristics excited by fluorescent agents within a patient, thereby inherently increasing the operational efficiency. (Id.)
Allowable Subject Matter
Claims 2, 3, 6, 8-12, 14, 15, 18, 22 and 23
Claims 2, 3, 6, 8-12, 14, 15, 18, 22 and 23 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
As set forth above, the prior art of record teaches the most salient features of a method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties. Specifically, the prior art of record teaches and/or renders obvious a method performing the steps of the claim requirements of independent claims 1 and 7.
Allowability of dependent claims 2 and 8 are indicated because none of the prior art of record teaches or fairly suggests a method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties with all of the equation claim requirements of dependent claims 2 and 8.
Allowability of dependent claims 3 and 9 are indicated because none of the prior art of record teaches or fairly suggests a method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties with all of the equation claim requirements of dependent claims 3 and 9.
Allowability of dependent claims 6 and 12 are indicated because none of the prior art of record teaches or fairly suggests a method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties with all of the equation claim requirements of dependent claims 3 and 9.
Allowability of dependent claim 14 is indicated because none of the prior art of record teaches or fairly suggests a method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties with all of the equation claim requirements of dependent claim 14.
Allowability of dependent claim 15 is indicated because none of the prior art of record teaches or fairly suggests a method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties in which the transforming the IFagent signals corresponding to the post-equilibration portion of the measurement data set to the rate of change of the IFagent signals step comprises: 1) log-transforming the IFagent signals at each corresponding data acquisition time; and 2) performing a linear regression of the log-transformed IFagent signals as a function of the corresponding data acquisition time to obtain a slope; wherein the slope represents the rate of change of the IFagent signals.
Allowability of dependent claim 22 is indicated because none of the prior art of record teaches or fairly suggests a method of monitoring a time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties in which removing the effects of autofluorescence contribution further comprises forward projecting a IFauto signal, representing the autofluorescence signal after the administration of the exogenous fluorescent agent, by combining the IFauto value with at least of one of the DRexmeas, a DRem signal and DRem,filtered signals, wherein the signals are obtained after administration of the exogenous fluorescent.
Claims 10, 11, 18 and 23 are similarly deemed as having allowable subject matter based on their dependency from dependent claims 8, 9 and 22, respectively.
Response to Arguments
Specification Objection(s)
Applicant contends that the May 2026 Spec Amendment overcomes the outstanding issues as set forth in the Feb 2026 Final Office Action. (May 2026 Response at 17).
The Examiner respectfully disagrees. First, the May 2026 Spec Amendment does resolve many Specification issues. However, as set forth above, based upon the May 2026 Spec Amendment, the Examiner finds that the instant ‘879 Reissue Application still has outstanding Specification Objection issues present. (See § VII., supra).
Drawings Objection(s)
Applicant contends that the May 2026 Drawings Amendment overcomes the outstanding issues as set forth in the Feb 2026 Final Office Action. (May 2026 Response at 17).
The Examiner respectfully disagrees. First, the May 2026 Drawings Amendment does resolve many Drawings issues. However, as set forth above, based upon the May 2026 Drawings Amendment, the Examiner finds that the instant ‘879 Reissue Application still has outstanding Drawings Objection issues present. (See § VIII., supra).
Claim Objection(s)
Applicant contends that the May 2026 Response properly provides sufficient explanation of support for the May 2026 Claim Amendment. (May 2026 Response at 17).
The Examiner respectfully agrees. However, as set forth above, based upon the May 2026 Claim Amendment, the Examiner finds that the instant ‘879 Reissue Application still has outstanding Claim Objection issues present. (See § IX., supra).
35 U.S.C. § 112 Rejections
35 U.S.C.§ 112(a)-(b) Rejections
Applicant contends that the May 2026 Claim Amendment overcomes all of the 35 U.S.C. 112(a)-(b) rejections. (May 2026 Response at 17-18).
The Examiner finds that May 2026 Response, including the May 2026 Claim Amendment, has been fully considered and is persuasive. Thus, the Examiner withdraws the corresponding U.S.C. 112(a)-(b) rejections.
35 U.S.C. § 251 Rejections
Broadening Claim Issues
Applicant contends that the May 2026 Claim Amendment overcomes the broadening of the claims issues, and thus, requests the withdrawal of the 35 U.S.C. 251 rejection. (May 2026 Response at 18-19).
The Examiner finds that May 2026 Response, including the May 2026 Claim Amendment, has been fully considered and is persuasive. Thus, the Examiner withdraws the corresponding U.S.C. 251 rejections.
35 U.S.C. § 103 Rejections
Since the prior at of Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) is commonly owned, Applicant contends that Heinrich cannot be utilized by the Office for prior rejection purposes. (May 2026 Response at 19-21).
The Examiner finds that May 2026 Response has been fully considered and is persuasive. Thus, the Examiner withdraws the corresponding 35 U.S.C. 103 rejections over Heinrich. However, the Examiner presents new 35 U.S.C. 103 rejections over Zand et al. (U.S. Publication No. 2016/0073909) (“Zand”).
Conclusion
Applicant is respectfully reminded that any suggestions or examples of claim language provided by the Examiner are just that—suggestions or examples—and do not constitute a formal requirement mandated by the Examiner. To be especially clear, any suggestion or example provided in this Office Action (or in any future office action) does not constitute a formal requirement mandated by the Examiner.
Should Applicant decide to amend the claims, Applicant is also reminded that—like always—no new matter is allowed. The Examiner therefore leaves it up to Applicant to choose the precise claim language of the amendment in order to ensure that the amended language complies with 35 U.S.C. § 112(a).
Independent of the requirements under 35 U.S.C. § 112(a), Applicant is also respectfully reminded that when amending a particular claim, all claim terms must have clear support or antecedent basis in the specification. See 37 C.F.R. § 1.75(d)(1) and MPEP § 608.01(o). Should Applicant amend the claims such that the claim language no longer has clear support or antecedent basis in the specification, an objection to the specification may result. Therefore, in these situations where the amended claim language does not have clear support or antecedent basis in the specification and to prevent a subsequent ‘Objection to the Specification’ in the next office action, Applicant is encouraged to either (1) re-evaluate the amendment and change the claim language so the claims do have clear support or antecedent basis or, (2) amend the specification to ensure that the claim language does have clear support or antecedent basis. See again MPEP § 608.01(o) (¶3). Should Applicant choose to amend the specification, Applicant is reminded that—like always—no new matter in the specification is allowed. See 35 U.S.C. § 132(a). If Applicant has any questions on this matter, Applicant is encouraged to contact the Examiner via the telephone number listed below.
Applicant is reminded of the obligation to apprise the Office of any prior or concurrent proceedings in which the ‘854 Patent is or was involved, such as interferences or trials before the Patent Trial and Appeal Board, other reissues, reexaminations, or litigations and the results of such proceedings.
In accordance with MPEP § 1406, the Examiner has reviewed and considered the prior art cited or ‘of record’ in the original prosecution of the ‘854 Patent. Applicant is reminded that a listing of the information cited or ‘of record’ in the original prosecution of the ‘854 Patent need not be resubmitted in this reissue application unless Applicant desires the information to be printed on a patent issuing from this reissue application.
Applicant is further reminded of the continuing obligation under 37 C.F.R. §1.56 to timely apprise the Office of any information which is material to patentability of the claims under consideration in this reissue application.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN J RALIS whose telephone number is (571)272-6227. The examiner can normally be reached on Monday-Friday 8:30am-5:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Hetul Patel can be reached on 571-272-4184. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Stephen J. Ralis/Primary Examiner, Art Unit 3992 Conferees:
/Luke S. Wassum/
Primary Examiner, Art Unit 3992
/H.B.P/Hetul PatelSupervisory Patent Examiner, Art Unit 3992
SJR
07/282026
1 The Examiner notes that all of claims 1-12,14-15 and 17-23 stood rejected under 112(a), 112(b) and 251; and claims 1, 4, 5, 7, 17 and 19-21 stood rejected under 103.
2 Claims 2-4, 8-10, 14 and 15 amended in the Nov 2025 Claim Amendment.
3 Claim 11 amended in the Nov 2025 Claim Amendment; and claims 1, 5-7 and 12 amended in the Feb 2023 Claim Amendment.
4 Claims 17-23 amended in the Nov 2025 Claim Amendment.
5 The Examiner notes that all of the Rejected Claims stood rejected under 112(a), 112(b) and 251; and claims 1, 4, 5, 7, 17 and 19-21 stood rejected under 103.
6 Claims 2-4, 8, 9 and 15 amended in the instant May 2026 Claim Amendment.
7 Claims 1, 5-7 and 12 amended in the instant May 2026 Claim Amendment; and claims 10 and 14 amended in the Nov 2025 Claim Amendment.
8 Claim 11 amended in the Nov 2025 Claim Amendment.
9 Claims 17-23 amended in the instant May 2026 Claim Amendment.
10 Claim 20 amended in the Nov 2025 Claim Amendment.
11 The ‘854 Patent discloses Figure 24 having “first and second detector apertures 1004/1006.” (See ‘854 Patent at c.54, ll.33-39). However, Figure 24 of the May 2026 Drawings Amendment does not have the elements. Applicant should place elements “1004” and “1006” in a newly Amended Figure 24 to indicate the “first and second detector apertures.
12 Id.
13 The ‘854 Patent discloses “[s]tep sizes may be selected at 1404 for the ranges of values selected for each power (bkx, bkm, bkmFilt).” However, element “1404” is not shown as such in the Figures of the ‘854 Patent. Applicant should place element “”1404” back in c.5, l.58 – c.6, l.8) and amend this portion of the ‘854 Patent appropriately.
14 See § VII, supra (i.e. the Examiner finds that: 1) 2104 should be the “sharp increase;” 2) 2106 should instead be the “peak concentration;” and 3) 2108 should be the “relatively smooth exponential decrease back to background fluorescence levels. (See ‘854 Patent at c.49, ll.51-67; see Figure 21).
Prosecution Insights