DETAILED ACTION
Contents
I. Notice of Pre-AIA or AIA Status 4
II. Priority 4
III. Pertinent Prosecution History 4
IV. Claim Status 5
V. Reissue Requirements 6
VI. Specification Objections 7
VII. Drawings Objections 8
VIII. Claim Objections 10
IX. Claim Interpretation 11
A. Lexicographic Definitions 12
B. 35 U.S.C. § 112 6th Paragraph 12
X. Claim Rejections – 35 U.S.C. § 112 13
A. 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph 13
(1) New Matter 13
B. 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph 20
XI. Broadening of Examined Claims 23
A. Broadening of Examined Claims’ Limitations 23
(1) Claim 1-6 and 19-23 23
(2) Claim 7-12, 14 and 17-18 26
(3) Claim 15 28
XII. Claim Rejections – 35 U.S.C. § 251 30
A. Broadened Claims 30
XIII. Claim Rejections – 35 U.S.C. § 103 30
A. Claims 1 and 19 are rejected under 35 U.S.C. 103 as obvious over Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) in view of Takaoka (U.S. Publication No. 2010/0268091) and Rabito (U.S. Publication No. 2003/0215391). 31
B. Claims 4, 5, 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) 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”). 35
C. Claim 1 is rejected under 35 U.S.C. 103 as obvious over Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) 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”). 38
D. Claim 7 is rejected under 35 U.S.C. 103 as obvious over Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) in view of Takaoka (U.S. Publication No. 2010/0268091), Rabito (U.S. Publication No. 2003/0215391), Rajagopalan et al. (U.S. Patent No. 7,674,902)(“ Rajagopalan”) and Dorshow et al., “Noninvasive Fluorescence Detection of Hepatic and Renal Function” (Dorshow”). 40
E. Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) in view of Takaoka (U.S. Publication No. 2010/0268091) and Rabito (U.S. Publication No. 2003/0215391), 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”). 49
F. Claim 7 is rejected under 35 U.S.C. 103 as obvious over Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) in view of Takaoka (U.S. Publication No. 2010/0268091), Rabito (U.S. Publication No. 2003/0215391), 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”). 51
XIV. Allowable Subject Matter 53
A. Claims 2, 3, 6, 8-12, 14, 15, 18, 22 and 23 53
XV. Response to Arguments 55
A. Oath/Declaration Issue 55
B. Specification Objection(s) 56
C. Drawings Objection(s) 57
D. Claim Objection(s) 57
E. 35 U.S.C. § 112 Rejections 58
(1) 35 U.S.C.§ 112(a) Rejections 58
(2) 35 U.S.C.§ 112(b) Rejections 59
F. 35 U.S.C. § 251 Rejections 60
(1) Broadening Claim Issues 60
G. 35 U.S.C. § 103 Rejections 61
XVI. Conclusion 62
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.
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 1-24 (“Rejected Claims”) 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.
Claim Status
The Examiner finds that the claim status in the instant ‘879 Reissue Application is as follows:
Claim(s) 2-4, 8-10, 14 and 15 (Original and twice amended)
Claim(s) 1, 5-7, 11, 12 (Original and amended)
Claim(s) 13 and 16 (Original and canceled)
Claim(s) 17-23 (New and 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 proceed-ing 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.5, ll.47-48, 52, the ‘854 Patent provides disclosure to “intervening tissues 114.” The ‘854 Patent further recites “intervening tissue 114” without the “s” numerous times throughout the ‘854 Patent. The Examiner recommends that Applicant choose either “tissues” or – tissue –, and amend the specification accordingly.
In c.9, l.58, the ‘854 Patent provides disclosure to “an electrical cable.” The ‘854 Patent further recites “the cable” without the “electrical” descriptor numerous times throughout the ‘854 Patent. The Examiner recommends that Applicant choose either “electrical cable” or – cable –, and amend the specification accordingly.
In c.41, l.54, the disclosure to “… the corrected Fir signal data …” should instead read – … the corrected Flr signal data … – (emphasis added).
In c.42, l.54, the disclosure to “… the corrected Fir signal data …” should instead read – … the corrected Flr signal data … – (emphasis added).
The Examiner finds that the above issues are representative. The Examiner finds that the ‘854 Patent is replete with multiple and numerous instances of typographical issues. Thus, Applicant must review the entirety of the ‘854 Patent to ensure the ‘854 Patent does not include any typographical issues.
Drawings Objections
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(4) because reference character:
“1404” has been used to designate both “the measured raw fluorescence signal obtained after the injection of the endogenous fluorescent agent (i.e. Flrmeas 1404)” and “[s]tep sizes may be selected at 1404 for the ranges of values selected for each power (bkx, bkm, bkmFilt);
“902” has been used to designate both a “light source well” and a “source well;”
“908/910” has been used to designate both a “detection wells” and a “detector wells.”
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: 1004a, 1006a, 1606, 21045, 2220, 2220a, etc.
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference sign(s) mentioned in the description: 2212a, 2214a, 2218a, etc.
Similarly, the Examiner finds that the ‘854 Patent describes a signal as
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(see ‘854 Patent at Abstract; c.3, ll.16-23 (Figures 19A, 19B), c.3, ll.46-51 (Figures 27, 28)) however the Figures (i.e., Figures 19A, 19B, 27 28, etc.) utilize the reference sign “DRex” instead. The Examiner finds that Applicant must amend the various figures in the ‘854 Patent to utilize –
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– instead of “DRex” in order to provide clear and consistent disclosure of the invention.
The Examiner finds that the above issues are representative. The Examiner finds that the ‘854 Patent is replete with multiple and numerous instances of drawings/specification issues. Thus, Applicant must review the entirety of the ‘854 Patent to ensure the ‘854 Patent does not include any drawings/specification issues.
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
MPEP § 1453 states,
pursuant to 37 CFR 1.173(c), each claim amendment must be accompanied by an explanation of the support in the disclosure of the patent for the amendment (i.e., support for all changes made in the claim(s), whether insertions or deletions). The failure to submit an explanation will generally result in a notification to applicant that the amendment before final rejection is not completely responsive (see 37 CFR 1.135(c)).
(MPEP § 1453; emphasis added). The Examiner finds that Applicant has not provided sufficient explanation of support for at least the amendments to claims instantly provided in the Feb 2023 Claim Amendment, as set forth in 37 CFR 1.173(c). (Id.) While the Feb 2023 Preliminary Amendment provides direction for the Examiner to find support for the claim amendments, the Examiner finds that the direction is not sufficient. Specifically, the Examiner finds that appropriate explanation of support in accordance with Rule 1.173(c) – with reference to particular passages and/or figures in the specification, and preferably on a claim-by-claim and limitation-by-limitation basis – is required. (Emphasis added).
In addition, the Nov 2025 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 amended new claims 17-23 are indicated as “(New)” when instead they 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. § 112
35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
New Matter
Claims 1-12, 14, 15 and 17-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 7
With respect to claims 1 and 7, the Examiner finds that claim 1 recites, in part,
providing a measurement data set comprising a plurality of measurement data entries, each measurement data entry comprising at least two measurements … comprising an Flr signal detected at a third region adjacent to the diffuse reflecting medium, and at least one DR signal selected from:
a DRex signal detected at a second region … by an unfiltered light detector during illumination of the diffuse reflecting medium by excitatory-wavelength light from the first region …;
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 at the third region by the filtered light detector during illumination of the diffuse reflecting medium by emission-wavelength light from the first region;…
transforming the Flr 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 Flr signal and removing the effects of autofluorescence contribution from the Flr signal; and
monitoring the corrected Flr signal for each measurement data entry within the post-agent-administration portion of the measurement data set.6
(Nov 2025 Claim Amendment at claim 1; emphasis added). Similarly, the Examiner finds that claim 7 recites, in part,
providing a measurement data set comprising a plurality of measurement data entries, each measurement data entry comprising at least two measurements … comprising an Flr signal detected at a third region adjacent to the diffuse reflecting medium, and at least one DR signal selected from:
a DRex signal detected at a second region … by an unfiltered light detector during illumination of the diffuse reflecting medium by excitatory-wavelength light from the first region …;
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 at the third region by the filtered light detector during illumination of the diffuse reflecting medium by emission-wavelength light from the first region;…
transforming each Flr signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent a corrected fluorescent signal, wherein the transforming comprises removing at least one of the effects of leak-through of excitation-level light into the Flr signal and removing the effects of autofluorescence contribution from the Flr signal; and
signal representing a corrected fluorescence intensity emitted by the exogenous fluorescent agent from within the diffuse reflecting medium, wherein transforming the Flr signal comprises at least one of removing the effects of leak-through of excitation-level light into the Flr signal and removing the effects of autofluorescence contribution from the Flr signal.
(Id. at claim 7; emphasis added). The Examiner finds that claims 2-6, 8-12, 14, 15 and 17-23 further recite the claim requirements of: 1) Flr signal; and 2) the DRex signal. (Id. at claims 2-6, 8-12, 14, 15 and 17-23).
With respect to the “1” (i.e., the Flr signal), the Examiner finds that recitation to the method comprising providing an Flr signal, broadly, detected at a third region adjacent to the diffuse reflecting medium is not sufficiently described in the ‘854 Patent. To support the Examiner’s position, the Examiner finds that the ‘854 Patent states,
[t]he measured raw fluorescence signal obtained after the injection of the endogenous fluorescent agent (i.e. Flrmeas 1404) may include the intensity of the fluorescence emitted by the endogenous fluorescent agent (Flragent ) superimposed over the background signal 1402 (i.e. Fauto and ExLT).
(‘854 Patent at c.6, ll.3-8; see Figure 14). In addition, the ‘854 Patent states,
[t]o remove the contribution of excitation light, the excitation leakthrough is taken to be a fraction of the diffuse reflectance excitation (
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) signal, where a universal calibration factor, CExLT, determines the fraction of the signal to subtract from Flrmeas as expressed below:
ExLT= CExLT *
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where CExLT is a calibration factor that is obtained by computing the ratio between the excitation light detected by both detectors on a non-fluorescing optical phantom as described below:
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This signal is then subtracted from Flrmeas to provide a fluorescence signal due only to fluorescent photons as expressed below:
Flrphotons = Flrmeas −ExLT
(Id. at c.38, l.61 – c.39, l.15; also see Abstract, c.42, ll.65-67 and c.44, l.67 – c.45, l.12). From this perspective, the Examiner finds that Flrmeas is most definitely a measurement signal obtained, whereas Flrphotons is a measurement signal that is determined from Flrmeas and not a measurement obtained. (Id.) Accordingly, the fluorescence measurements obtained by the method does not include fluorescence measurements determined by the method (i.e., Flrmeas is obtained and Flrphotons is not).
Thus, as such, the Examiner concludes that there is insufficient indication in the specification that Applicant had possession of a method comprising a memory comprising providing an Flr signal, broadly, detected at a third region adjacent to the diffuse reflecting medium, as recited.
With respect to the “2” (i.e., the DRex signal), the Examiner finds that recitation to the method comprising providing an DRex signal, broadly, detected at a second region … by an unfiltered light detector during illumination of the diffuse reflecting medium is not sufficiently described in the ‘854 Patent. To support the Examiner’s position, the ‘854 Patent states,
In an aspect, if the system 200 is used to obtain CExLT, Flrmeas and
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are from a non-fluorescent, homogeneous phantom in the context of the system 200 as described herein above.
(‘854 Patent at c.44, l.67 – c.45, l.3; emphasis added). Similarly, the Examiner finds that the ‘854 Patent further discloses the system 200 explicitly measuring the raw fluorescence, Flrmeas, and the various diffuse reflection signals (i.e.,
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, DRem , DRem,filtered ). (Id. at Abstract; c.3, ll.16-23 (Figures 19A, 19B), 46-51 (Figures 27, 28). Similarly, as with respect to the discussion regarding the “Flr signal” above, the Examiner finds that other “DRex” signals (i.e.,
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,
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and DRexphotons
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are determined based on various intrinsic characteristic of the various measurement signals. (Id. at c.37, ll.5-15; c.45, ll.38-52). From this perspective, the Examiner finds that
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is most definitely a measurement signal obtained, whereas
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,
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and DRexphotons are measurement signals that are determined from
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, and other various signals, and not measurements obtained. (Id.) Accordingly, the diffuse reflection measurement obtained by the method does not include diffuse reflection measurements determined by the method (i.e.,
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is obtained and
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and DRexphotons are not).
Thus, as such, the Examiner concludes that there is insufficient indication in the specification that Applicant had possession of a method comprising a memory comprising providing an DRex signal, broadly, detected at a second region … by an unfiltered light detector during illumination of the diffuse reflecting medium, as recited.
Claims 2-6, 8-12, 14, 15 and 17-23 are similarly rejected based on its dependency from independent claims 1 and 7.
Claims 2, 3, 6, 8, 9 and 12
With respect to claims 2, 3, 6, 8, 9 and 12, the Examiner finds that claims 2, 3, 6, 8, 9 and 12 recite equations with the variables DRex and Flr. (Feb 2023 Claim Amendment at claims 2, 3, 6, 8, 9 and 12). However, in examination of the equations in the ‘854 Patent the equations do not include the variables DRex and Flr. (See ‘854 Patent at Equations 21-23). Accordingly, the diffuse reflection measurement obtained by the method does not include any equations with the variables DRex and Flr.
Thus, as such, the Examiner concludes that there is insufficient indication in the specification that Applicant had possession of a method comprising the utilization of Equations with the variables DRex and Flr, as recited.
Claims 3, 6 and 10-12 are similarly rejected based on its dependency from dependent claims 2, 8 and 9.
Claims 4, 5, 17, 18, 21 and 23
With respect to claims 4, 5, 17, 18, 21 and 23, the Examiner finds that claims 4 and 17 recite,
wherein the removing the effects of autofluorescence contribution comprises determining IFauto, representing intrinsic autofluorescence emitted by endogenous chromophores within the diffuse reflecting medium by determining a value of the Flr 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.
(Nov 2025 Claim Amendment at claims 4 and 17; emphasis added); the Examiner finds that claims 5 recites,
wherein removing the effects of autofluorescence contribution further comprises subtracting the IFauto signal from the Flr signal.
(Id. at claim 5; emphasis added); the Examiner finds that claim 18 recites,
wherein the removing the effects of autofluorescence contribution further comprises subtracting the IFauto signal from Flr to obtain the IFagent signal.
(Id. at claim 18; emphasis added); and the Examiner finds that claims 21 and 23 recite,
wherein the removing the effects of autofluorescence contribution further comprises subtracting the IFauto signal from the Flr signal to obtain the IFagent signal.
(Id. at claims 21 and 23; emphasis added). The Examiner finds that recitations to the method comprising: 1) removing the effects of autofluorescence comprises determining IFauto by determining a value of the Flr signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent; 2) subtracting the IFauto signal from the Flr signal; and 3) subtracting the IFauto signal from the Flr signal to obtain the IFagent signal are not sufficiently described in the ‘854 Patent. To support the Examiner’s position, the Examiner finds that claim 4 was originally dependent from claims 2 and 3, thus, requiring the certain mathematical calculation to determine certain terms in order to attain Flrphotons. (‘854 Patent at original claims 1-3). Specifically, original claim 4 determined the IFauto by taking the mean, median, mode or trimmed mean value of the collection of Flrphotons determined. (Id. at claim 3; also see c.40, l.17 – c.41, l.67; c.47, ll.38-47; see Figure 18).
As set forth above, the Examiner finds that the Flr signals broadly include both the Flrmeas and Flrphotons signals. (See § X.A.(1).(a), supra). From this perspective, amended claim 4, and now new claim 17, broadly recite determining a mean or median value of the Flrmeas and/or Flrphotons signals. However, as noted above, the determined Flrphotons signals, and not the obtained Flrmeas signals, are utilized to determine a value for IFauto. Accordingly, the determining of IFauto by determining a value of the Flr signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent includes only the Flr signals determined (i.e., Flrphotons) and not the Flr signals obtained (i.e., Flrmeas). Similarly, since the determined IFauto can only be subtracted from the determined (i.e., Flrphotons) and not the Flr signals obtained (i.e., Flrmeas), this applies to claims 5, 18, 21 and 23 as well.
Thus, as such, the Examiner concludes that there is insufficient indication in the specification that Applicant had possession of a method comprising: 1) removing the effects of autofluorescence comprises determining IFauto by determining a value of the Flr signals, broadly, over a portion of the measurement dataset obtained prior to administration of the fluorescent agent; 2) subtracting the IFauto signal from the Flr signal, broadly; and 3) subtracting the IFauto signal from the Flr signal, broadly, to obtain the IFagent signal, as recited.
Claims 5 is also additionally rejected based on its dependency from dependent claim 4.
35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The 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 U.S.C. 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.
Claims 1-12, 14, 15 and 17-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 1 and 7 recite the limitation “… an Flr signal….” The Examiner finds that claims 2-6, 8-12, 14, 15 and 17-23 further recite “the Flr signal. The Examiner finds it unclear and indefinite as to what exactly the claim requirement “Flr signal” is. Further clarification is required to precisely recite exactly what an “Flr signal” is. The Examiner recommends Applicant amend “… an Flr signal…” to – … an fluorescence emission (Flr) signal…–. The claims will be examined as such.
Similarly, claims 1 and 7 recite the limitation “… at least one DR signal….” The Examiner finds that claims 2-6, 8-12, 14, 15 and 17-23 further recite variations of the “DR signal.” The Examiner finds it unclear and indefinite as to what exactly the claim requirement “DR signal” is. Further clarification is required to precisely recite exactly what an “DR signal” is. The Examiner recommends Applicant amend “DR signal” to – … at least one diffuse reflection (DR) signal…–. The claims will be examined as such.
Claims 2-6, 8-12, 14, 15 and 17-23 are rejected in light of their dependency from at least independent claims 1 and 7.
Claims 1 and 7 recite the limitation “Flr” signal. The Examiner finds that claims 3, 6, 9, and 12 further recite equations utilizing “Flr” signal as a variable. In examination of the ‘854 Patent, since the Flrmeas is most definitely a measurement signal obtained, the Examiner finds it unclear and indefinite to what exactly the obtained “Flr” signal is. (‘854 Patent at Abstract; c.6, ll.3-8; c.42, ll.65-67; c.44, l.67 – c.45, l.12; also see § X.A.(1).(a), supra, for further explanation). The Examiner recommends Applicant amend “Flr signal” to – …Flrmeas signal…–
Similarly, claims 1 and 7 recite the limitation “DRex” signal. The Examiner finds that claims 2, 6, 8 and 12 further recite equations utilizing “DRex” signal as a variable. In examination of the ‘854 Patent, since the obtained diffuse refection excitatory measurement signal is actually defined as “
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” not “DRex,” the Examiner finds it unclear and indefinite to what exactly the obtained “DRex” signal is. (‘854 Patent at Abstract; c.3, ll.16-23 (Figures 19A, 19B), 46-51 (Figures 27, 28); c.44, l.67 – c.45, l.3); also see § X.A.(1).(a), supra, for further explanation). The Examiner recommends Applicant amend “DRex signal” to – …
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signal…–.
Claims 2-6, 8-12, 14, 15 and 17-23 are rejected in light of their dependency from at least independent claims 1 and 7.
Claims 2 and 8 recite the limitation “… transforming each DRex signal into an ExLT signal….” First, it is unclear and indefinite to what exactly an “ExLT” signal is. The Examiner recommends Applicant amend “… ExLT signal…” to – … excitation-wavelength light leak-through (ExLT) signal … –.
In addition, it is unclear and indefinite to how removing the effects from the Flr signal can transform each DRex signal when there is only one DRex signal, and not a plurality of DRex signals in each Flr signal. The Examiner recommends Applicant amend “each DRex signal” to – the DRex signal –. The Examiner further notes that “DRex signal” has its own issues, as asserted above.
Claim 5 recites the limitation “removing the effects of….” The Examiner finds that the preceding claims recites “removing the effects…”. The Examiner finds it unclear and indefinite to whether these steps are the same or different. Further clarification is required to either provide proper antecedent basis or further differentiate the claim requirements. The Examiner recommends Applicant amend: “removing the effects of …” to – … said/the removing the effects of …–.
Claim 1 recites the limitation “the corrected Flr signal in line 29. Claim 7 recites the limitation "the diffuse reflecting medium" in lines 6-7, 10-13, 15, 18 and 24; and claims 10, 17 and 20 recite the limitation "the diffuse reflecting medium" in line 3. Claim 18 recites the limitation “IFauto” in line 2. Claim 21 recites the limitation “the IFagent signal” in line 2. There is insufficient antecedent basis for these limitations in the claims.
Claim 12 recites the limitation “the fluorescence signal Flr representing emission-wavelength fluorescence measured using the filtered light detector” and claim 18 recites the limitation “Flr.” The preceding claims recites the limitation “an Flr signal detected at a third region adjacent to the diffuse reflecting medium.” It is unclear and indefinite to the metes and bounds/scope of the claim requirement “Flr.” Further clarification is required to either provide proper antecedent basis or further differentiate the claim requirements.
In general, the claims are replete with such 35 U.S.C. 112, second paragraph issues. The above notes are exemplary with respect to all of the 35 U.S.C. 112, second paragraph rejections present in the instant case, all claims must be carefully reviewed and appropriate corrections should be made in response to this rejection.
The Examiner finds that because claims 1-12, 14, 15 and 17-23 are indefinite under 35 U.S.C. §112 second paragraph as outlined above, it is impossible to properly construe claim scope at this time. See e.g. Honeywell International Inc. v. ITC, 68 USPQ2d 1023, 1030 (Fed. Cir. 2003) (“Because the claims are indefinite, the claims, by definition, cannot be construed.”). However, in accordance with MPEP § 2173.06 and the USPTO’s policy of trying to advance prosecution by providing art rejections even though these claims are indefinite, the claims are construed and the art is applied as much as practically possible.
Broadening of Examined Claims
Broadening of Examined Claims’ Limitations
Claim 1-6 and 19-23
As set forth infra, the Examiner further finds that claim 1 enlarges the scope of the patent, i.e., a claim which is greater in scope than each and every claim of the original patent.
Specifically, the Examiner finds that amended original claim 1 (“RI Claim 1”) of the instant ‘879 Reissue Application recites, in part,
providing a measurement data set comprising a plurality of measurement data entries, each measurement data entry comprising at least two measurements … comprising an Flr signal detected at a third region adjacent to the diffuse reflecting medium, and at least one DR signal selected from:
a DRex signal detected at a second region … by an unfiltered light detector during illumination of the diffuse reflecting medium by an excitatory-wavelength light from the first region …;
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 at the third region by the filtered light detector during illumination of the diffuse reflecting medium by emission-wavelength light from the first region;…
transforming the Flr 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 Flr signal and removing the effects of autofluorescence contribution from the Flr signal; and
monitoring the corrected Flr signal for each measurement data entry within the post-agent-administration portion of the measurement data set.
(“Broad RI Claim 1 FLR Signal,” “Broad RI Claim 1 DR Signal” and “Broad RI Claim 1 Transforming Step”; Feb 2023 Claim Amendment at claim 1; emphasis added). The Examiner finds that now patented claim 1 of the ‘854 Patent (“Patent Claim 1”), in part, recites,
providing a measurement data set comprising a plurality of measurement data entries, each measurement data entry comprising at least two measurements … comprising an Flrmeas (fluorescence emission) signal detected at a third region adjacent to the diffuse reflecting medium, and at least one DR signal selected from:
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signal detected at a second region … by an unfiltered light detector during illumination of the diffuse reflecting medium by excitatory-wavelength light from the first region …;
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 at the third region by the filtered light detector during illumination of the diffuse reflecting medium by emission-wavelength light from the first region;…
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 autofluorescence contribution to the Flrmeas signal;
monitoring the IFagent for each measurement data entry within the post-agent-administration portion of the measurement data set.
(“Narrow RI Claim 1 FLR Signal,” “Narrow RI Claim 1 DR Signal” and “Narrow RI Claim 1 Transforming Step”; ‘854 Patent, claim 1; emphasis added).
The Examiner finds that the Broad RI Claim 1 FLR Signal, Broad RI Claim 1 DR Signal and Broad RI Claim 1 Transforming Step are broader than the Narrow RI Claim 1 FLR Signal, Narrow RI Claim 1 DR Signal and Narrow RI Claim 1 Transforming Step. Specifically, the Examiner finds that the: 1) Broad RI Claim 1 FLR Signal does not have the requirement of the signal being an “Flrmeas (fluorescence emission) signal (see Feb 2023 Claim Amendment at claim 1 with replacement of “Flrmeas (fluorescence emission) signal” with “Flr signal”) (“RI Claim 1-6 FLR Signal Omission”)7; 2) Broad RI Claim 1 DR Signal does not have the requirement of the signal being a “
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signal” (see Feb 2023 Claim Amendment at claim 1 with replacement of “
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signal” with “DRex”) (“RI Claims 2/6/19/22 DR Signal Omission”) 8; and 3)” Broad RI Claim 1 Transforming Step does not have the requirement of transforming the Flrmeas signal to an “IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium” (see Feb 2023 Claim Amendment at claim 1 with replacement of “IFagent (intrinsic fluorescence) signal…” with “corrected fluorescence signal”) (“RI Claim 1 Transforming Step Omission”);
Thus, since the RI Claims 1-6 FLR Signal Omission, RI Claims 1/2/6/19/22 DR Signal Omission and RI Claim 1 Transforming Step Omission provide claims which are broader/greater in scope than each and every claim of the original patent, the Examiner concludes that at least RI Claim 1 is broadened reissue claim as compared to the claims of the ‘854 Patent.
Claim 7-12, 14 and 17-18
As set forth infra, the Examiner further finds that claim 7 enlarges the scope of the patent, i.e., a claim which is greater in scope than each and every claim of the original patent.
Specifically, the Examiner finds that amended original claim 7 (“RI Claim 7”) of the instant ‘879 Reissue Application recites, in part,
providing a measurement data set comprising a plurality of measurement data entries, each measurement data entry comprising at least two measurements … comprising an Flr signal detected at a third region adjacent to the diffuse reflecting medium, and at least one DR signal selected from:
a DRex signal detected at a second region … by an unfiltered light detector during illumination of the diffuse reflecting medium by excitatory-wavelength light from the first region …;
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 at the third region by the filtered light detector during illumination of the diffuse reflecting medium by emission-wavelength light from the first region;…
transforming each Flr signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent signal representing a corrected fluorescence intensity emitted by the exogenous fluorescent agent from within the diffuse reflecting medium, wherein transforming the Flr signal comprises at least one of removing the effects of leak-through of excitation-level light into the Flr signal and removing the effects of autofluorescence contribution from the Flr signal;
(“Broad RI Claim 7 FLR Signal,” “Broad RI Claim 7 DR Signal” and “Broad RI Claim 7 Transforming Step”; Feb 2023 Claim Amendment at claim 7; emphasis added). The Examiner finds that now patented claim 7 of the ‘854 Patent (“Patent Claim 7”), in part, recites,
providing a measurement data set comprising a plurality of measurement data entries, each measurement data entry comprising at least two measurements … comprising an Flrmeas (fluorescence emission) signal detected at a third region adjacent to the diffuse reflecting medium, and at least one DR signal selected from:
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signal detected at a second region … by an unfiltered light detector during illumination of the diffuse reflecting medium by excitatory-wavelength light from the first region …;
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 at the third region by the filtered light detector during illumination of the diffuse reflecting medium by emission-wavelength light from the first region;…
transforming each 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 transforming each the Flrmeas signal comprises at least one of removing the effects of leak-through of excitation-level light into the Flrmeas signal and removing the autofluorescence contribution to the Flrmeas signal;
(“Narrow RI Claim 7 FLR Signal,” “Narrow RI Claim 7 DR Signal” and “Narrow RI Claim 7 Transforming Step”; ‘854 Patent, claim 7; emphasis added).
The Examiner finds that the Broad RI Claim 7 FLR Signal, Broad RI Claim 7 DR Signal and Broad RI Claim 7 Transforming Step are broader than the Narrow RI Claim 7 FLR Signal, Narrow RI Claim 7 DR Signal and Narrow RI Claim 7 Transforming Step. Specifically, the Examiner finds that the: 1) Broad RI Claim 7 FLR Signal does not have the requirement of the signal being an “Flrmeas (fluorescence emission) signal (see Feb 2023 Claim Amendment at claim 7 with replacement of “Flrmeas (fluorescence emission) signal” with “Flr signal”) (“RI Claims 7-9/12/17/18 FLR Signal Omission”)9; 2) Broad RI Claim 7 DR Signal does not have the requirement of the signal being a “
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signal” (see Feb 2023 Claim Amendment at claim 7 with replacement of “
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signal” with “DRex”) (“RI Claim 7/8/12 DR Signal Omission”) 10; and 3)” Broad RI Claim 7 Transforming Step does not have the requirement of transforming the Flrmeas signal to an IFagent (intrinsic fluorescence) signal representing a detected fluorescence intensity emitted solely by the fluorescent agent from within the diffuse reflecting medium” (see Feb 2023 Claim Amendment at claim 7 with replacement of “detected” with “corrected” and “emitted solely by” with “emitted by ) (“RI Claim 7 Transforming Step Omission”);
Thus, since the RI Claim 7-9/12/17/18 FLR Signal Omission, RI Claim 7/8/12 DR Signal Omission and RI Claim 7 Transforming Step Omission provide claims which are broader/greater in scope than each and every claim of the original patent, the Examiner concludes that at least RI Claim 7 is broadened reissue claim as compared to the claims of the ‘854 Patent.
Claim 15
As set forth infra, the Examiner further finds that claim 15 enlarges the scope of the patent, i.e., a claim which is greater in scope than each and every claim of the original patent.
Specifically, the Examiner finds that amended original claim 15 (“RI Claim 15”) of the instant ‘879 Reissue Application recites, in part,
wherein 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:
log-transforming the IFagent signals at each corresponding data acquisition time; and
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.
(“Broad RI Claim 15 Slope Characteristic”; Feb 2023 Claim Amendment at claim 15; emphasis added). The Examiner finds that now patented claim 15 of the ‘854 Patent (“Patent Claim 15”), in part, recites,
wherein 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:
log-transforming the IFagent signals at each corresponding data acquisition time; and
performing a linear regression of the log-transformed IFagent signals as a function of the corresponding data acquisition time to obtain a slope;
inverting the slope to obtain the RDTC, wherein RDTC represents the rate of change of the IFagent signals.
(“Narrow RI Claim 15 Slope Characteristic”; ‘854 Patent, claim 15; emphasis added).
The Examiner finds that the Broad RI Claim 15 Slope Characteristic is broader than the Narrow RI Claim 15 Slope Characteristic. Specifically, the Examiner finds that the Broad RI Claim 15 Slope Characteristic does not have the requirement of inverting the slope to obtain the RDTC in which the RDTC represents that rate of change of the IFagent signals (see Feb 2023 Claim Amendment at claim 15 with replacement of “inverting the slope to obtain the RDTC wherein the RDTC represents …” with “the slope represents”) (“RI Claim 15 Slope/RDTC Omission”).
Thus, since the RI Claim 15 Slope/RDTC Omission provide claims which are broader/greater in scope than each and every claim of the original patent, the Examiner concludes that at least RI Claim 15 is broadened reissue claim as compared to the claims of the ‘854 Patent.
Claim Rejections – 35 U.S.C. § 251
Broadened Claims
Claims 1-12, 14, 15 and 17-23 are rejected under 35 U.S.C. 251 as being broadened in a reissue application filed outside the two year statutory period. The Examiner finds that at least amended original claims 1, 7 and 15 are broadened with the removal of the various omitted claimed requirements as set forth above. (See § XI.A, supra). A claim is broader in scope than the original claims if it contains within its scope any conceivable product or process which would not have infringed the original patent. A claim is broadened if it is broader in any one respect even though it may be narrower in other respects.
Claim Rejections – 35 U.S.C. § 103
35 USC § 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 Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) 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 Heinrich discloses a method of determining an organ (i.e., kidney) function utilizing an exogenous fluorescent indicator and monitoring the fluorescence from the tissue of a patient. (Heinrich at Abstract; ¶¶ 0001, 0014-0015, 0019-0022, 0025-0026, 0029-0033).
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 an Flr 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 signal selected from:
a DRex 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 Heinrich discloses an excitation light providing an illumination that irradiates an exogenous fluorescent indicator within the tissue of a patient. (Heinrich at ¶¶ 0047-0049, 0072, 0083-0085). The Examiner finds that Heinrich discloses sensors providing data (i.e.. signals) obtained by “transcutaneously measuring fluorescence indicator compound” of various regions within the patient’s tissue before and after the introduction of the exogenous fluorescent indicator to the patient. (Id.)
Heinrich discloses all 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 a 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 a 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 Heinrich.
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
Heinrich and Takaoka discloses all 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 Heinrich 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 Flr 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 Flr signal and removing the effects of autofluorescence contribution from the Flr signal; and
In this regard, the Heinrich discloses measuring fluorescence before and after the introduction of a fluorescence indicator. (Heinrich at Abstract; ¶¶ 0001, 0014-0015, 0019-0022, 0025-0026, 0029-0033). In addition, the Examiner finds that Heinrich teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “background fluorescence” and subtracting this “background fluorescence” from the values measured at the other times. (Id. at ¶ 0026). Since the “background fluorescence” 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 “background fluorescence” would be equivalent to the effects of autofluorescence contribution from the Flr signal.”
monitoring the corrected Flr signal for each measurement data entry within the post-agent-administration portion of the measurement data set.
In this regard, the Heinrich discloses the corrected measurements being recorded and further processed. (Id. at ¶¶ 0044-0045).
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 Flr signal with at least of one of the DRex, 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 Heinrich teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “background fluorescence” and subtracting this “background fluorescence” from the values measured at the other times. (Id. at ¶ 0026). The Examiner finds that the this “background fluorescence” would inherently include the Flr signal and at least one of the DRex, 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 Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) 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 Flr 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, Heinrich teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “background fluorescence” and subtracting this “background fluorescence” from the values measured at the other times. (See § XIII.A.(1).(c), supra, also see Heinrich at ¶ 0026).
Heinrich, Takaoka and Rabito discloses all 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 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 Heinrich, 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 removing the effects of autofluorescence contribution further comprises subtracting the IFauto from the Flr signal.
[21] wherein the removing the effects of autofluorescence contribution further comprises subtracting the IFauto from the Flr signal to obtain the IFagent signal.
As set forth above, Heinrich teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “background fluorescence” and subtracting this “background fluorescence” from the values measured at the other times. (See § XIII.A.(1).(c), supra, also see Heinrich at ¶ 0026).
Claim 1 is rejected under 35 U.S.C. 103 as obvious over Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) 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 Heinrich, Takaoka and Rabito teaches and/or renders obvious all the claim requirements of claim 1. (See § XIII.A.(1), supra).
However, to the degree a reviewing body finds that it is not inherent that Heinrich teaches “transforming the Flr 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 autofluorescence contribution from the Flr signal,” the following alternative to this feature is provided as set forth below:
As set forth above, the Examiner finds that Heinrich discloses the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “background fluorescence” and subtracting this “background fluorescence” from the values measured at the other times. (Id. at ¶ 0026)
Heinrich, Takaoka and Rabito discloses all the limitations, as previously set forth, except for specifically calling for transforming the Flr 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 Flr signal and removing the effects of autofluorescence contribution from the Flr signal.
However, transforming the Flr 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 Flr signal and removing the effects of autofluorescence contribution from the Flr 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 Flr 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 the effects of autofluorescence contribution from the Flr 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 Heinrich. Takaoka and Rabito.
A person of ordinary skill in the art would be motivated to incorporate transforming the Flr 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 the effects of autofluorescence contribution from the Flr 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 Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) in view of Takaoka (U.S. Publication No. 2010/0268091), Rabito (U.S. Publication No. 2003/0215391), 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 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 Heinrich discloses a method of determining an organ (i.e., kidney) function utilizing an exogenous fluorescent indicator and monitoring the fluorescence from the tissue of a patient. (Heinrich at Abstract; ¶¶ 0001, 0014-0015, 0019-0022, 0025-0026, 0029-0033).
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 an Flr 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 signal selected from:
a DRex 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 Heinrich discloses an excitation light providing an illumination that irradiates an exogenous fluorescent indicator within the tissue of a patient. (Heinrich at ¶¶ 0047-0049, 0072, 0083-0085). The Examiner finds that Heinrich discloses sensors providing data (i.e.. signals) obtained by “transcutaneously measuring fluorescence indicator compound” of various regions within the patient’s tissue before and after the introduction of the exogenous fluorescent indicator to the patient. (Id.)
Heinrich discloses all 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 a 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 a 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 Heinrich.
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
Heinrich and Takaoka discloses all 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 Heinrich 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 each Flr signal of each measurement data entry within the post-agent-administration portion of the measurement data set to an IFagent signal representing a corrected fluorescence intensity emitted by the exogenous fluorescent agent from within the diffuse reflecting medium, wherein transforming the Flr signal comprises at least one of removing the effects of leak-through of excitation-level light into the Flr signal and removing the effects of autofluorescence contribution from the Flr signal ;
In this regard, the Heinrich discloses measuring fluorescence before and after the introduction of a fluorescence indicator. (Heinrich at Abstract; ¶¶ 0001, 0014-0015, 0019-0022, 0025-0026, 0029-0033). In addition, the Examiner finds that Heinrich teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “background fluorescence” and subtracting this “background fluorescence” from the values measured at the other times. (Id. at ¶ 0026). Since the “background fluorescence” 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 “background fluorescence” would be equivalent to the effects of autofluorescence contribution from the Flr signal.”
identifying a post-equilibration portion of the measurement data set;
In this regard, Heinrich, 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 Heinrich 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 Heinrich discloses the corrected measurements being recorded and further processed to determine the renal function. (Id. at ¶¶ Abstract; 0044-0045).
Heinrich, Takaoka and Rabito discloses all 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 Heinrich, Takaoka and Rabito.
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 (Heinrich, Takaoka and Rabito) 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 Heinrich, Takaoka and Rabito 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 Heinrich, Takaoka and Rabito 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 Heinrich, Takaoka and Rabito, 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 Heinrich, Takaoka and Rabito 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 Heinrich, Takaoka and Rabito 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 Heinrich, 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 Heinrich, 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 Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) in view of Takaoka (U.S. Publication No. 2010/0268091) and Rabito (U.S. Publication No. 2003/0215391), 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 Flr 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, Heinrich teaches the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “background fluorescence” and subtracting this “background fluorescence” from the values measured at the other times. (See § XIII.A.(1).(c), supra, also see Heinrich at ¶ 0026).
Heinrich, Takaoka, Rabito, Rajagopalan and Dorshow discloses all 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 Flr 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 signals over a portion of the measurement dataset obtained prior to administration of the fluorescent agent in Heinrich, Takaoka, Rabito, Rajagopalan and Dorshow with determining a mean value from a plurality of measurements of the Flr 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 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 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 Heinrich et al. (U.S. Publication No. 2016/0249808)(“Heinrich”) in view of Takaoka (U.S. Publication No. 2010/0268091), Rabito (U.S. Publication No. 2003/0215391), 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 Heinrich, Takaoka, Rabito, 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 Heinrich teaches “transforming the Flr 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 autofluorescence contribution from the Flr signal,” the following alternative to this feature is provided as set forth below:
As set forth above, the Examiner finds that Heinrich discloses the fluorescence value measured at the first time, prior to introduction of the fluorescence indicator, as the “background fluorescence” and subtracting this “background fluorescence” from the values measured at the other times. (Id. at ¶ 0026)
Heinrich, Takaoka, Rabito, Rajagopalan and Dorshow discloses all the limitations, as previously set forth, except for specifically calling for transforming the Flr 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 Flr signal and removing the effects of autofluorescence contribution from the Flr signal.
However, transforming the Flr 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 Flr signal and removing the effects of autofluorescence contribution from the Flr 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 Flr 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 the effects of autofluorescence contribution from the Flr 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 Heinrich, Takaoka, Rabito, Rajagopalan and Dorshow.
A person of ordinary skill in the art would be motivated to incorporate transforming the Flr 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 the effects of autofluorescence contribution from the Flr 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 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112 and 251 set forth in this Office action.
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 DRex, 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
Oath/Declaration Issue
Applicant contends that the Feb 2023 Oath/Declaration is sufficient and complies with the direction provided in 37 CFR 1.175 and MPEP § 1414. (Nov 2025 Response at 10-11).
With respect to the defective Feb 2023 Oath/Declaration, the Examiner finds that the Nov 2025 Response has been fully considered and is persuasive. Thus, the Examiner withdraws the defective Feb 2023 Oath/Declaration determination and correlating 35 U.S.C. 251 rejection.
Specification Objection(s)
Applicant contends that amending the specification with respect “… the corrected Fir signal data …” and “cable” is not required. (Nov 2025 Response at 11). Since the Office is “required to indicate how rejections may be overcome and how problems may be resolved,” Applicant contends that they have not been provided enough direction to correct issues with the Specification. (Id. at 11-12)
The Examiner respectfully disagrees. First the Nov 2025 Spec Amendment does resolve several Specification issues. However, as set forth above, based upon the Nov 2025 Spec Amendment, the Examiner finds that the instant ‘879 Reissue Application still has outstanding Specification Objection issues present from the Specification Objection issues provided in the previous Aug 2025 Non-Final Office Action. (See § VI, supra).
With respect to the ‘854 Patent being replete with typographical errors, the Examiner has provided Applicant several examples of issues that are within the ‘854 Patent. The Examiner finds that the ‘854 Patent has fifty-nine (59) columns of disclosure and over twenty-nine (29) Figures. The Examiner finds that the direction of “whenever practicable…” does not apply to the Specification objections because of the sheer size of the Application. Thus, Applicant must review the entirety of the ‘854 Patent to ensure the ‘854 Patent does not include any typographical issues.
Drawings Objection(s)
Since the Office is “required to indicate how rejections may be overcome and how problems may be resolved,” Applicant contends that they have not been provided enough direction to correct issues with the Drawings. (Nov 2025 Response at 12-13).
The Examiner respectfully disagrees. First, the Examiner finds that Applicant made no amendments to the Specification, nor the Drawing to address the issues provided to Applicant in the previous Aug 2025 Non-Final Office Action, Thus, the instant ‘879 Reissue Application still has outstanding Drawing Objection issues present from the Drawings Objection issues provided in the previous Aug 2025 Non-Final Office Action. (See § VII, supra).
With respect to the ‘854 Patent being replete with multiple issues/errors, the Examiner has provided Applicant several examples of issues that are within the ‘854 Patent. The Examiner finds that the ‘854 Patent has fifty-nine (59) columns of disclosure and over twenty-nine (29) Figures. The Examiner finds that the direction of “whenever practicable…” does not apply to the Drawings objections because of the sheer size of the Application. Thus, Applicant must review the entirety of the ‘854 Patent to ensure the ‘854 Patent does not include any drawing/specification issues.
Claim Objection(s)
Since Applicant cited to sections of the ‘854 Patent to support the claim amendments, Applicant contends that the explanation of support provided by Applicant for the claim amendments is sufficient. (Nov 2025 Response at 13-14).
The Examiner respectfully disagrees. The MPEP states,
Also pursuant to 37 CFR 1.173(c), each claim amendment must be accompanied by an explanation of the support in the disclosure of the patent for the amendment (i.e., support for all changes made in the claim(s), whether insertions or deletions).
(MPEP § 1453.II). The Examiner finds that a broad explanation of support stating “support for the amendments to original claims 1-12 and 14-15, and new claims 17-23, is provided throughout the specification and claims, for instance, at least in…” is not specific to insertion, nor deletions. (Nov 2025 Response at 13). Thus, the Examiner finds that appropriate explanation of support in accordance with Rule 1.173(c) – with reference to particular passages and/or figures in the specification, and preferably on a claim-by-claim and limitation-by-limitation basis – is required. (Emphasis added).
35 U.S.C. § 112 Rejections
35 U.S.C.§ 112(a) Rejections
Applicant contends that c.42, ll.4-34 of the ‘854 Patent provides sufficient support for claim requirement Flr signal not being new matter. (Nov 2025 Response at 14-15).
The Examiner respectfully disagrees. The Examiner finds that the citation provided by Applicant actually support the Examiner’s position. Specifically, the ‘854 Patent references Flr as being “”the measured florescence signal,” not a broad Flr signal that could include Flrphotons or other florescence signals. Thus, the Examiner concludes and maintains that the “Flr signal” claim requirement is new matter, as set forth above.
With respect to the claim requirement of “the DRex signal,” Applicant provided no arguments to the new matter rejection. Thus, the Examiner concludes and maintains that the “DRex signal” claim requirement is new matter, as set forth above.
35 U.S.C.§ 112(b) Rejections
Applicant contends that the Nov 2025 Claim Amendment satisfies the antecedent basis issues. (Nov 2025 Response at 15-16). In addition, since the Office is “required to indicate how rejections may be overcome and how problems may be resolved,” Applicant contends that they have not been provided enough direction to correct issues with the indefinite claim issues. (Id. at 16). Moreover, Applicant contends that the claim requirements “Flr signal” and “DRex signal” are clear. (Id.)
The Examiner respectfully disagrees. First, with respect to antecedent basis claim issues, the Examiner finds that the amendments to claims 2-4, 8-11 and 17-23 overcome the 35 U.S.C. 112(b) rejections provided in the Aug 2025 Non-Final Office Action. However, in light of the Nov 2025 Claim Amendment, the Examiner finds that there is an outstanding 35 U.S.C. 112(b) rejections still present. (See § X.B, supra).
With respect to the ‘854 Patent being replete with multiple 35 U.S.C. 112(b)issues/rejections, the Examiner has provided Applicant several examples of issues that are within the ‘854 Patent. The Examiner finds that the ‘854 Patent has fifty-nine (59) columns of disclosure and over twenty-nine (29) Figures. The Examiner finds that the direction of “whenever practicable…” does not apply to the 35 U.S.C. 112(b)issues/rejections because of the sheer size of the Application. Thus, Applicant must review the entirety of the ‘854 Patent to ensure the ‘854 Patent does not include any 35 U.S.C. 112(b)issues/rejections issues.
With respect to the contention that the claim requirements “Flr signal” and “DRex signal” are definite, the Examiner respectfully disagrees. The Examiner has provided Applicant with a detailed analysis to why the claim requirements “Flr signal” and “DRex signal” are indefinite. (See § X.B, supra). Applicant has simply provided a statement, without sufficient support from the ‘854 Patent, to support Applicant’s contention. Thus, the Examiner concludes and maintains that the “Flr signal” and “DRex signal” claim requirement are indefinite, as set forth above.
35 U.S.C. § 251 Rejections
Broadening Claim Issues
Applicant states,
[t]he present claims do not broaden the terms of the patent. Rather, they make corrections for consistency with the descriptions of the present application. The claims comply with the written description requirement and are not indefinite as described above.
(Nov 2025 Response at 17). Applicant further contends that RDTC may be replaced with the claim language of claim 15. (Id.) Moreover, Applicant contends that claims 17-23 cannot be broadening claims because the substance of the claims are not broadened. (Id.)
The Examiner respectfully disagrees. The test for whether broadening is present is not dependent on whether said corrections (i.e., claim amendments) are being made for consistency with the description, but to whether the corrections (i.e., claim amendments) enlarge the scope of the patent, i.e., a claim which is greater in scope than each and every claim of the original patent. As set forth above, the Examiner has provided sufficient support that both the Feb 2023 Claim Amendment and the Nov 2025 Claim Amendment have broadened the ‘854 Patent claims. (See § XI.A.1-2, supra). Thus, the Examiner concludes and maintains that the claims in Nov 2025 Claim Amendment are broadened, as set forth above.
With respect to claim 15, the Examiner finds that new claim 15 limitation clearly removes performing an inverting step to obtain the RDTC value. Thus, the Examiner concludes and maintains that the RI Claim 15 Slope/RDTC Omission broadens claim 15, as set forth above. (See § XI.A.3, supra)
With respect to claims 17-23, while the Examiner agrees that claims 17-23 provide new claim requirements, the Examiner finds that claims 17-23 still recite the claim requirements “Flr signal” and “DRex signal,” hence claims 17-23 still comprise broadened claim requirements similarly as the other claims do. (See § XI.A.1-2, supra).
35 U.S.C. § 103 Rejections
Applicant contends that the present claims are patentable over the prior are because Applicant does not agree with the claim interpretation. (Nov 2025 Response at 18-19).
The Examiner respectfully disagrees. The Examiner finds Applicant’s contention just a statement without any evidence to support the statement. Thus, the Examiner concludes and maintains the 35 U.S.C. 103 rejections, as set forth above. (See § XIII, supra).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Because this application is now final, Applicant are reminded of the USPTO’s after final practice as discussed in MPEP §714.12 and §714.13 and that entry of amendments after final is not a matter of right. “The refusal of an examiner to enter an amendment after final rejection of claims is a matter of discretion.” In re Berger, 279 F.3d 975, 984, 61 USPQ2d 1523, 1529 (Fed. Cir. 2002) (citations omitted). Furthermore, 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. Unless stated otherwise by an express indication that a claim is “allowed,” exemplary claim language provided by the Examiner to overcome a particular rejection or to change claim interpretation has not been addressed with respect to other aspects of patentability (e.g. §101 patentable subject matter, §112, first paragraph written description and enablement, §112, second paragraph indefiniteness, and §102 and §103, prior art). Therefore, any claim amendment submitted under 37 C.F.R. §1.116 that incorporates an Examiner suggestion or example or simply changes claim interpretation will nevertheless require further consideration and/or search and a patentability determination as noted above.
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 1st paragraph.
Independent of the requirements under 35 U.S.C. § 112 1st paragraph, 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.
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 Monday-Friday 8:30am-5:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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
2/06//2026
1 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.
2 Claims 2-4, 8-10, 14 and 15 amended in the instant Nov 2025 Claim Amendment.
3 Claim 11 amended in the instant 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 instant Nov 2025 Claim Amendment.
5 In addition, 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).
6 The claim requirement is only in claim 1.
7 The Examiner finds that claims 2-6 similarly recite the Flr signal instead of the “Flrmeas (fluorescence emission) signal.
8 The Examiner finds that claims 2, 6, 19 and 22 similarly recite the DRex signal instead of the “
D
R
e
x
m
e
a
s
signal.”
9 The Examiner finds that claims 8, 9, 12, 17 and 18 similarly recite the Flr signal instead of the “Flrmeas (fluorescence emission) signal.”
10 The Examiner finds that claims 8 and 12 similarly recite the DRex signal instead of the “
D
R
e
x
m
e
a
s
signal.”
Prosecution Insights