DETAILED ACTION
Applicant’s response, filed 24 Sept. 2025 has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
Status of Claims
Claims 4-5 and 17 are cancelled.
Claims 1-3, 6-16, and 18-20 are pending.
Claims 18-19 are no longer withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim based on the claim amendment filed 24 Sept. 2025. Claims 18-19 are now drawn to the elected species. Election was made without traverse in the reply filed on 15 Feb. 2025.
Claims 1-3, 6-16, and 18-20 are rejected.
Claim 15 is objected to.
Priority
Any newly recited portions are necessitated by claim amendment.
Applicant’s claim for the benefit of a prior-filed application, U.S. Provisional App. No. 63/983,045 filed 28 Feb. 2020, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/983,045 (herein after ‘045), fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Independent claim 1, and claims dependent therefrom, recite “…analyzing the baseline-corrected Raman spectrum to detect the presence of and/or quantify a condition of the subject by analyzing peak position, height and/or area under the curve of one or more peaks of interest”. Dependent claim 4 specifies the condition can be any of bladder cancer, acute cystitis, prostate cancer, etc. Claim 6 “…analyzing the transformed, baseline-corrected Raman spectrum and determining that the sample is classified as being from a subject who has kidney disease and the extent of the disease thereof, and based on the extent of the disease state, administering subsequent dialysis treatment…”. However, App. ‘045 does not provide support for detecting a presence or quantifying a condition, including kidney disease, by analyzing peak position, height, and/or the area under the curve of peaks of interest, and/or administering dialysis treatment based on the determination as claimed.
At best, App. ‘045 at pg. 2, para. 1 of the introduction of the specification discloses that Raman spectroscopy generally has found applications in a variety of medical studies, such as diagnosis and monitoring therapy. However, the specification of App. ’045 provides no detail on how to analyze the baseline-corrected Raman spectrum to detect or, more specifically, quantify a condition of the subject. The specification of App. 045’ at pg. 10, para. 3 to pg. 11, para. 1 further discloses analyzing spectra collected in a hemodialysis experiment, and that hemodialysis is a common treatment for patients with kidney disease. The specification of App. ‘045 discloses wastes in the blood are released to dialysate in the chamber, and that peaks in the right end of the spectral domain of these samples can be associated with important molecules used in dialysate, which can cause trouble for quantitative analysis of the compositions used in dialysate samples. Thus, the specification of App. 045 discloses analyzing the composition of dialysate samples, but provides no guidance as to how the detect or quantify a condition of a subject based on the composition, let alone specifically by the recited analysis in the claims.
Instant claim 13 recites the Raman spectrum is from a fluid, tissue, gas, and/or solid. Furthermore, instant claim 14 recites the Raman Spectrum can be from a dialysate or urine sample. However, the specification of App. 045 does not provide support for analyzing a Raman Spectrum from a urine sample, or a tissue or gas. Instead App. ‘045 discloses analyzing a chemical compound or dialysate sample (i.e. fluid) (claims 5 and 10).
Accordingly, the effective filing date of claims 1-3, 6-16, and 20 is 01 March 2021.
Response to Arguments
Applicant's arguments filed 24 Sept. 2025 regarding priority have been fully considered but they are not persuasive.
Applicant remarks the limitations relating to position height and area of the Raman spectra have been removed and thus the claims should be entitled to the ‘045 application filing date (Applicant’s remarks at pg. 25, para. 1).
This argument is not persuasive. The disclosure of App. ‘045 does not provide any support for analyzing a baseline-corrected Raman spectrum to detect or quantify a bladder cancer or kidney disease in the subject, as explained in the above priority statement, and nor does Applicant point to support in the priority document for these limitations.
Drawings
The replacement drawing sheets filed 24 Sept. 2025 have been entered.
The previous objection to the drawings filed 01 March 2021 in the Office action mailed 24 March 2025 has been withdrawn in view of the replacement drawings received 24 Sept. 2025.
The replacement drawings received 25 Sept. 2025 are objected to for the following reasons. This objection is newly recited.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color (FIG. 1A-F). Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The amendments to the abstract received 24 Sept. 2025 have been entered. Support for the amendments are provided in Applicant’s remarks filed 24 Sept. 2025 at pg. 25, para. 4-5 pointing to particular paragraphs of references incorporated by reference into the originally filed specification.
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The following objection is previously recited:
The abstract of the disclosure is objected to because:
The abstract refers to the purported merits of the invention and compares the invention with the prior art.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Response to Arguments
Applicant remarks a corrected abstract is provided in response to the abstract being objected to for referring to the purported merits of the invention and therefore the objection should be withdrawn (Applicant’s remarks at pg. 28, para. 6-7).
This argument is not persuasive. The last line of the abstract recites “ISREA is simple, fast, and can yield consistent and accurate baselines that preserve all the meaningful Raman peaks”, which only serves to provide purported merits of the invention. Therefore, the objection is maintained.
Claim Objections
Claim 15 is objected to because of the following informalities. This objection is newly recited and necessitated by claim amendment.
Claim 15 recites “The method of claim 8, wherein:…(e) wherein i is a wave number…”, which is grammatically incorrect. The extraneous “wherein” in (e) should be removed, and an “and” should be placed between steps (d) and (e), such that claim 15 recites “The method of claim 8, wherein:…(d) repeating…; and (e)
Appropriate correction is required.
Claim Interpretation
Claim 1 recites “determining that the sample is classified as being from a subject i) who has bladder cancer…; or ii) who has kidney disease…”. In the response filed 15 Feb. 2025, Applicant elected, without traverse, the species of “chronic kidney failure” from Group I, as acknowledged in the Office action mailed 24 March 2025. Therefore, the embodiment in which the sample is determined to have kidney disease is being examined herein.
Claim 3 similarly recites “…wherein the determining the sample is classified as being from a subject who has bladder cancer is performed in a manner…”, which further limits the optional embodiment of determining the subject has bladder cancer of claim 1. Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. See MPEP 21111.04 I. As discussed above, the embodiment in which the subject is determined to have kidney disease is being examined herein, and thus the step of determining the sample has bladder cancer is not required by claims 1 or 3.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-3 and 18-19 are rejected under 35 U.S.C. 112(a) 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, at the time the application was filed, had possession of the claimed invention. This rejection is newly recited and necessitated by claim amendment.
Claim 1, and claims dependent therefrom, recite “analyzing the baseline-corrected Raman spectrum of the sample and determining the sample is classified as being from a subject i) who has bladder cancer…; and administering cystoscopy to the subject whose sample has been classified as being from a subject who has bladder cancer”.
Applicant’s remarks at pg. 26, para. 4 states that support for administering cystoscopy is provided by new paragraph [0109]. However, Applicant’s specification at para. [0109] merely discloses “A definitive diagnosis for each patient presenting with clinical signs indicative of BCA was made using…direct visualization (cystoscopy) and a confirmation biopsy. The definitive diagnosis was used to classify urine specimens for subsequent RametrixTM analysis”. However, this does not provide support for analyzing a Raman spectrum to classify a subject has having bladder cancer and then administering cystoscopy to the patient based on the Raman spectrum indicating bladder cancer. Instead, this merely provide support for using cystoscopy to confirm a subject has bladder cancer before analyzing their Ramen spectrum (i.e. for subsequent RametrixTM analysis).
For the reasons discussed above, the specification does not provide a sufficient disclosure of the limitation above recited in claims 1-3 and 18-19 to demonstrate to one of ordinary skill in the art that the inventor possessed the invention at the time the application was filed. THS IS A NEW MATTER REJECTION. For more information regarding the written description requirement, see MPEP §2161.01- §2163.07(b).
Claim Rejections - 35 USC § 112(b)
The rejection of claims 3-5 under 35 U.S.C. 112(b) in the Office action mailed 25 March 2025 has been withdrawn in view of claim amendments and cancellations received 24 Sept. 2025.
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.
Claims 6-7 and 15-16 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. Any newly recited portion is necessitated by claim amendment.
Claim 6, and claims dependent therefrom, are indefinite for recitation of “(a) applying an iterative fitting procedure…; (b) in each iteration prediction errors are adjusted….; (c) applying smoothing splines to the new set of intensities to obtain a new baseline estimate and calculating a new set of prediction errors….; (d) and repeating the fitting procedure and stopping when errors fall…”. Overall, it is unclear which steps of claim 6 are intended to be a part of the “iterative fitting procedure” in (a). Claim 6 recites a separate step “ (b) in each iteration, prediction errors are adjusted…to form a new set of intensities”, which implies the iterative fitting procedure only includes the adjusting of prediction errors. However, the next step recites smoothing spines are applied to these new intensities to obtain a new baseline estimate and a new set of prediction errors are calculated, and the last step requires repeating the fitting procedure until errors fall below a desired level, implying the errors (i.e. the new set of prediction errors) change on each iteration and thus are part of the iteration. As a result, it is unclear if the “(c) applying smoothing splines” is part of the iterative fitting procedure, as suggested by step (d), or not part of the iterative fitting procedure as suggested by (b). If this applying step (c) is not part of the iterative fitting procedure, such that it is not repeated in the final step of “repeating the fitting procedure”, it is further unclear in what way the repeating of the fitting procedure is intended to stop if new prediction errors are not calculated. For purpose of examination, the claims will be interpreted to mean that the applying smoothing spines is part of the iterative fitting procedure. If Applicant agrees with this interpretation, it is suggested Applicant amends the claims to clarify which steps are part of the iterative procedures, such as by amending the claims to recite “…(a) applying an iterative fitting procedure…, comprising, in each iteration: (b) adjusting down prediction errors through a root…; and (c) applying smoothing splines…”. Any substep of the iteration (e.g. steps (b) and (c)) should be indented further relative to step (a) and step (d).
Claim 15 is indefinite for recitation of “The method of claim 8 wherein:…(b) adjusting the intensity values, such that areas with zero or negative intensity deviations….remain the same, while areas with positive intensity deviations; (c) feeding the new intensities…; repeating….”. The limiting effect of the wherein clause is unclear because claim 15 does not recite any verb or action relating to the step of “adjusting the intensity values…” recited in claim 8. For example, it is unclear if claim 15 intends to require that “(b) the adjusting the intensity values is performed such that….” (similar to how step (a) is amended) such that claim 15 further limits how the adjusting is performed in claim 8. Alternatively it is unclear if this is intended to be a separate step of adjusting the intensity values of the baseline estimate than the adjustment made in claim 8. See MPEP 2111.04. With further respect to (c)-(d), the limiting effect of “wherein:…(c) feeding…” and “wherein:…(d) repeating…” are similarly unclear. As previously discussed, steps (a)-(c) in claim 15 appear to correspond to the steps (a)-(c) in claim 8, albeit in more detail in claim 15, and furthermore step (d) in each of claims 15 and 8 is repeated until a certain deviation is met. As a result, it is not clear if the “(d) repeating one or more of steps (a)-(c)”, and thus steps (a)-(c) generally, are intended to require a separate performance and iteration in addition to the performance of (a)-(c) and iteration in (d) of claim 8, or if claim 15 simply intends to further limit steps (a)-(d) of claim 8. If Applicant intends for steps (a)-(d) in claim 15 to correspond to those in claim 8, to overcome the rejection, claim 15 should be amended to use wherein clauses where appropriate to properly further limit positively recited steps of claim 8. For example “The method of claim 8, wherein: (b) comprises adjusting…; (c) comprises feeding…; (d) comprises repeating…”.
Response to Arguments
Applicant's arguments filed 24 Sept. 2025 regarding 35 U.S.C. 112(b) regarding the outstanding rejections above have been fully considered but they are not persuasive.
Applicant remarks that Applicant has made the appropriate amendments regarding claim 6 due to claim 6 being unclear as to which steps are part of the iterative fitting procedure (Applicant’s remarks at pg. 28, para. 8).
This argument is not persuasive because claim 6 still does not clearly indicate which steps are part of the iterative fitting procedure as explained in the above rejection. Suggestions were proposed to overcome the rejection above.
Applicant remarks that claim 15 is amended to use wherein clauses as suggested by the Examiner to properly limit positively cited steps of claim 8 (Applicant’s remarks at pg. 29, para. 4).
This argument is not persuasive. Applicant simply added a “wherein” to the first line of claim 15, which resulted in grammatically incorrect and unclear phrases. Therefore, claim 15 is still indefinite for the reasons discussed in the above rejection, and a suggestion is made above to overcome the rejection.
Claim Rejections - 35 USC § 101
The rejections of claims 4-5 and 17 under 35 U.S.C. 101 in the Office action mailed 24 Sept. 2025 has been withdrawn in view of the cancellation of these claims received 24 Sept. 2025.
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3, 6-16, and 18-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and/or law of nature without significantly more. Any newly recited portion is necessitated by claim amendment.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355). Applicant is also directed to MPEP 2106.
Step 1: The instantly claimed invention (claims 1, 6, and 8 being representative) is directed to a method for analyzing Raman spectrum data. Therefore, the instantly claimed invention falls into one of the four statutory categories. [Step 1: YES]
Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A, Prong 1: Under the MPEP § 2106.04, the Step 2A (Prong 1) analysis requires determining whether a claim recites an abstract idea, law of nature, or natural phenomenon.
Claims 1 and 8 recite the following steps which fall under the mathematical concepts and/or mental processes groupings of abstract ideas:
obtaining a transformed, baseline-corrected Raman spectrum by baselining and transforming the Raman spectrum by (claim 1 only);
(a) obtaining a baseline estimate on the Raman spectrum by fitting smoothing splines to the Raman spectrum;
(b) determining a difference in intensity value at one or more wavenumber of the Raman spectrum as compared with a corresponding wavenumber of the baseline estimate;
(c) obtaining an adjusted baseline estimate by adjusting the intensity values of the baseline estimate where a positive difference is determined, or where there is a zero or negative difference determined, then the intensity value of the initial baseline estimate remains the same;
(d) iterating by repeating (a)-(c) on the adjusted baseline estimates; and (e) obtaining the transformed, baseline-corrected Raman spectrum by repeating (d) until a desired deviation between two consecutive adjusted baseline estimates is reached;
performing node optimization on the baseline-corrected Raman spectrum, wherein the node optimization: is performed in a manner to i) emphasize one or more peaks of interest, and ii) minimize other peak(s); and comprises placing a selected number of nodes to i) highlight regions of the Raman spectrum in which one or more compound(s) of interest appears, and/or ii) highlight one or more regions where the Raman spectrum and the baseline do not overlap (claim 1)/ performing node optimization on the transformed, baseline-corrected Raman spectrum by placing a selected number of nodes to highlight regions o the Raman spectrum in which one or more compound(s) of interest appears (claim 8);
analyzing the [transformed in claim 8] baseline-corrected Raman spectrum of the sample and determining that the sample is classified as being from a subject i) who has bladder cancer, and the severity or stage of the bladder cancer (claim 1 only); or ii) has kidney disease and the extent of the disease state thereof (claims 1 and 8)
Claim 6 recites the following steps which fall under the mathematical concepts and/or mental processes groupings of abstract ideas:
producing a transformed, baseline-corrected Raman spectrum by:
(a) applying an iterative fitting procedure to a Raman spectrum to adjust for peak invasion; (b) in each iteration, prediction errors are adjusted down through a root transformation and added back to fitted baseline intensities to form a new set of intensities;
(c) applying smoothing splines to the new set of intensities to obtain a new baseline estimate and calculating a new set of prediction errors based on the new baseline estimate;
(d) repeating the fitting procedure and stopping when errors fall below a desired level, such that a transformed, baseline-corrected Raman spectrum is obtained;
performing node optimization on the baseline-corrected Raman spectrum, wherein the node optimization: is performed in a manner to i) emphasize one or more peaks of interest, and ii) minimize other peak(s); and comprises placing a selected number of nodes to i) highlight regions of the Raman spectrum in which one or more compound(s) of interest appears, and/or ii) highlight one or more regions where the Raman spectrum and the baseline do not overlap; and
analyzing the transformed, baseline-corrected Raman spectrum and determining that the sample is classified as being from a subject who has kidney disease and the extent of the disease thereof.
The identified claim limitations falls into the mental process and/or mathematical concept groups of abstract ideas for the following reasons. In this case, the above step of (a) performing an iterative fitting of splines (e.g. piece-wise curves) to the Raman spectrum in claims 1 and 8 involves iteratively performing mathematical calculations such as addition and math to minimize a difference and can be practically performed in the mind aided with pen and paper. Thus this limitation recites a mental process and mathematical concept. The limitation of (b) determining a difference in claims 1 and 8 simply involves performing subtraction which is a mental process and mathematical concept. The step of (c) obtaining an adjusted baseline estimate by adjusting intensity values can be performed mentally by altering the values and further recites a mathematical concept by calculating positive, zero, or negative differences to determine the appropriate adjustment. Step (d)-(e) of iterating (a)-(c) in claims 1 and 8 recite both a mental process and mathematical concept for the same reasons applied to steps (a)-(c), and further recite the mental process and mathematical concept of determining the desired deviation (i.e. a subtraction) is reached. The step of performing node optimization further recites a mental process and by involving repeating of the fitting of splines while changing the number of knots/nodes to determine a best fit in order to emphasize peaks of interest, and then mentally evaluating the Raman spectrum to identify nodes and regions of the Raman spectrum with particular peaks for a compound. The step of analyzing the baseline-corrected Raman spectrum to detect kidney disease or bladder cancer further recites a mental process because it amounts to mentally analyzing the baseline-corrected spectrum to identify a signature corresponding to some disease. The steps of claim 6 similarly recites the mental process and mathematical concept of applying an iterative fitting procedure, adjusting prediction errors down through a root transformation and adding back to the fitted baseline intensities (i.e. mathematical operations), applying smoothing splines to the new set of intensities, repeating the process until errors fall below a desired level, performing node optimization, and analyzing the Spectrum to identify kidney disease for the same reasons discussed above for the steps in claims 1 and 8. Therefore, these limitations recite an abstract idea of a mental process and/or mathematical concept. See MPEP 2106.04(a)(2) I. and III.
Claims 1, 6, and 8 further recite a law of nature of a correlation between substances present in a sample of a subject (e.g. determined by Raman Spectroscopy) and the presence of kidney disease or cladder cancer in the subject.
Dependent claims 2-3, 7, 9-16, and 18-20 further recite an abstract idea and/or further limit the abstract idea of the independent claims. Dependent claim 2 further recites the mathematical concept and mental process of analyzing to comprise PCA, DAPC, PLS, and/or ANN to detect or quantify the condition. Dependent claim 3 further recites a mathematical concept and mental process of determining whether the baseline-corrected Raman spectrum is classified in (a) or (b) based on whether the spectrum is closer mathematically to one or the other statistically significant groups (a) or (b). Dependent claim 7 further limits the mathematical fitting process to comprise adjusting intensity values based on differences. Dependent claim 9 further limits the mental process and mathematical concept of adjusting of intensity values to be performed according to the recited mathematical relationship. Dependent claims 10-11 further limit the mental process and mathematical concept of iterating (d) until the desired deviation reaches a convergence criteria in the recited range. Dependent claim 12 further limits the mental process and mathematical concept of fitting smoothing splines to use a particular number of knots. Dependent claim 13-14 further limit the Raman spectrum being analyzed by claim 8, and thus are part of the abstract idea of claim 8. Dependent claim 15 further limits the mental process and mathematical concept of steps (a)-(d) of claim 8, and recites additional mathematical relationships. Claim 16 further recites a mathematical relationship and mental process of how the Raman spectrum is modeled. Dependent claims 18-19 further limit the mental process of performing node optimization of claim 1, and thus are part of the abstract idea. Dependent claim 20 further limits the mental process and mathematical concept of fitting smoothing splines by placing knots in particular areas. Therefore, claims 1-3, 6-16, and 18-20 recite an abstract idea and/or law of nature. [Step 2A, Prong 1: YES]
Step 2A: Prong 2: Under the MPEP § 2106.04, the Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. This judicial exception is not integrated into a practical application for the following reasons.
Claims 2-3, 7, 9-16, and 18-20 do not recite any elements in addition to the judicial exception.
The additional elements of claims 1 and 8 include:
obtaining a Raman spectrum from a sample from a subject; and
administering cystoscopy to the subject whose sample has been classified as being from a subject who has bladder cancer and confirming the severity or stage thereof (claim 1 only); or administering dialysis treatment to, or performing transplantation for, the subject who has kidney disease based on the extent thereof (claims 1 and 8)
The additional elements of claim 6 include:
obtaining a Raman spectrum from a sample from a subject receiving dialysis;
based on the extent of the disease state, administering subsequent dialysis treatment to the subject who has kidney disease by 1) increasing or decreasing the amount of time that the subject is on the dialyzer, 2) increasing or decreasing the blood flow through the dialyzer, or 3) a combination of those.
The additional element of obtaining a Raman spectrum from a sample only serves to collect information for use by the abstract idea, and thus amounts to insignificant extra-solution activity. See MPEP 2106.05(g), which does not integrate the recited judicial exception into a practical application.
Regarding claim 1, the step of “administering cystoscopy to the subject whose sample has been classified as being from a subject who has bladder cancer and confirming the severity or stage thereof” does not integrate the recited judicial exception into a practical application. MPEP 2106.04(d)(2) states one way to demonstrate such integration is when the additional elements apply or use the recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. The administration of “cystoscopy” does not actually treat or prevent bladder cancer. Instead, the administration of cystoscopy is merely a diagnostic procedure used to diagnose bladder cancer, thus merely confirming the results of the judicial exception of identifying bladder cancer. However, the judicial exception is not utilized in any particular way to actually inform or alter how the cytoscopy is being performed. Therefore this additional element amounts to insignificant extra-solution activity of an insignificant application, analogous to printing or downloading generated menus, Ameranth, 842 F.3d at 1241-42, 120 USPQ2d at 1854-55 or cutting hair after first determining the hair style, In re Brown, 645 Fed. App'x 1014, 1016-1017 (Fed. Cir. 2016).
Regarding claims 1 and 8, the administration of dialysis to or transplantation for the subject who has kidney disease does not integrate the judicial exception into a practical application of effecting a particular treatment for the following reasons. MPEP 2106.04(d)(2) states the treatment or prophylaxis limitation must have more than a nominal or insignificant relationship to the exception(s). MPEP 2106.04(d)(2) further explains examiners may find it helpful to evaluate other considerations such as the mere instructions to apply an exception consideration (see MPEP § 2106.05(f)), and the field of use and technological environment consideration (see MPEP § 2106.05(h)), when making a determination of whether a treatment or prophylaxis limitation is particular or general. Regarding, “mere instructions to apply an exception, MPEP 2106.05(f) explains the recitation of claim limitations that attempt to cover any solution to an identified problem with no restriction on how the result is accomplished and no description of the mechanism for accomplishing the result, does not integrate a judicial exception into a practical application or provide significantly more because this type of recitation is equivalent to the words "apply it". See Electric Power Group, LLC v. Alstom, S.A., 830 F.3d 1350, 1356, 119 USPQ2d 1739, 1743-44 (Fed. Cir. 2016).
First, claims 1 and 8 encompass only performing any transplantation in the subject (e.g. a heart transplant), and thus is not significantly related to the judicial exception of identifying kidney disease. Furthermore, the administration of dialysis treatment to a subject who has kidney disease further amounts to mere instructions to apply the exception in a generic way. Claims 1 and 8 are directed to an abstract idea of obtaining a transformed, baseline-corrected Raman Spectrum. The claims then broadly require “analyzing the baseline-corrected Raman spectrum” to determine the subject has kidney disease, and then, in an embodiment, require administering dialysis treatment to the subject. However, the claims do not recite any details regarding how the result of identifying kidney disease is accomplished and instead merely recite the idea of a solution of identifying and treating kidney disease by “analyzing” the corrected Raman spectrum. Therefore, the treatment step amounts to mere instructions to apply an exception.
In addition, the administration of dialysis treatment or transplantation merely link the abstract idea to a particular field of use of treating kidney disease. MPEP 2106.05(h) provides examples of limitations that the courts have described as merely indicating a field of use or technological environment in which to apply a judicial exception, including a step of administering a drug providing 6-thioguanine to patients with an immune-mediated gastrointestinal disorder, because limiting drug administration to this patient population did no more than simply refer to the relevant pre-existing audience of doctors who used thiopurine drugs to treat patients suffering from autoimmune disorders, Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 78, 101 USPQ2d 1961, 1968 (2012). Here the claims broadly link the abstract idea to an identification of kidney disease, as discussed above, and then merely refer to the pre-existing doctors who use dialysis to treat patients suffering from kidney disease.
Last, the administration of dialysis to the subject who has kidney disease by increasing or decreasing time on dialysis and/or increasing or decreasing blood flow through the dialyzer in claim 6 is not sufficient to integrate to the recited judicial exception into a practical application and instead amounts to mere instructions to apply an exception for the following reasons. Claim 6 involves obtaining a Raman spectrum from a sample of a subject already receiving dialysis, then broadly requires “analyzing the transformed, baseline-corrected Raman spectrum” to determine the sample has kidney disease and the severity of kidney disease, and finally increases or decreases the amount of dialysis the subject is receiving “based on the extent of the disease state”. Therefore, claim 6 attempts to cover any solution (i.e. analyzing) to identifying a kidney disease severity in a subject with no restriction on how the identification is made, and no description of how the Raman spectrum is analyzed to determine the extent of kidney disease, and then simply alters the dialysis treatment in the subject “based on the extent of the disease”, again with no details on how the dialysis treatment is intended to be altered based on the extent of the kidney disease. As a result, the administration step of claim 6 does not integrate a judicial exception into a practical application or provide significantly more because this type of recitation is equivalent to the words "apply it". See MPEP 2106.05(f).
Therefore, the additionally recited elements amount to insignificant extra-solution activity, mere instructions to apply an exception, and/or merely indicating a field of us, and, as such, the claims as a whole do no integrate the abstract idea into practical application. Thus, claims 1-3, 6-16 and 18-20 are directed to an abstract idea and/or law of nature. [Step 2A, Prong 2: NO]
Step 2B: In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP § 2106.05.
The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception.
Claims 2-3, 7, 9-16, and 18-20 do not recite any elements in addition to the judicial exception.
The additional elements of claims 1 and 8 include:
obtaining a Raman spectrum from a sample from a subject; and
administering cystoscopy to the subject whose sample has been classified as being from a subject who has bladder cancer and confirming the severity or stage thereof (claim 1 only); or administering dialysis treatment to, or performing transplantation for, the subject who has kidney disease based on the extent thereof (claims 1 and 8)
The additional elements of claim 6 include:
obtaining a Raman spectrum from a sample from a subject receiving dialysis;
based on the extent of the disease state, administering subsequent dialysis treatment to the subject who has kidney disease by 1) increasing or decreasing the amount of time that the subject is on the dialyzer, 2) increasing or decreasing the blood flow through the dialyzer, or 3) a combination of those.
Obtaining a Raman spectrum from a sample of a subject is well-understood, routine, and conventional. This position is supported by Applicant’s specification at para. [0004], which discloses Raman spectroscopy is an established tool for both qualitative and quantitative analysis of molecular composition of macro- and nano-materials and biological systems, citing a plurality of references.
Furthermore, administering dialysis to a subject with kidney disease, as recited in claims 1, 6, and 8, is well-understood, routine, and conventional. This position is supported by Collins et al. (The State of Chronic Kidney Disease, ESRD, and Morbidity and Mortality in the First Year of Dialysis, 2009, Clin J Am Soc Nephrol, 4, pg. S5-S11; newly cited). Collins reviews the state of kidney disease during the first year of dialysis (Abstract), and discloses the number of kidney disease patients on dialysis tripled from 1989 through 2007 (Abstract; pg. S5, col. 2, para. 2-3; Fig. 1), demonstrating the conventionality of the treatment. Collins further discloses durations of individual dialysis patients vary, demonstrating increased or decreased times on dialysis (pg. S8, col. 1, para. 2-3). Furthermore, simply increasing or decreasing how long the subject is on dialysis amounts to mere instructions to apply the exception, which cannot provide significantly more.. See Electric Power Group, LLC v. Alstom, S.A., 830 F.3d 1350, 1356, 119 USPQ2d 1739, 1743-44 (Fed. Cir. 2016); Intellectual Ventures I v. Symantec, 838 F.3d 1307, 1327, 120 USPQ2d 1353, 1366 (Fed. Cir. 2016); Internet Patents Corp. v. Active Network, Inc., 790 F.3d 1343, 1348, 115 USPQ2d 1414, 1417 (Fed. Cir. 2015).
Therefore, the claims as a whole do not amount to significantly more than the exception itself. [Step 2B: NO]
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea and/or natural correlation without significantly more. For additional guidance, applicant is directed generally to applicant is directed generally to the MPEP § 2106.
Response to Arguments
Applicant's arguments filed 24 Sept. 2025 regarding 35 U.S.C. 101 have been fully considered but they are not persuasive.
Applicant remarks that claims 1, 6, and 8 have been amended to recite various steps of treating a subject, and therefore, the rejection should be withdrawn (Applicant’s remarks at pg. 29, para. 6 to pg. 30, para. 2).
This argument is not persuasive for the reasons discussed in detail above under Step 2A, Prong 2 regarding the newly amended limitations of treating a subject. The limitations do not integrate the recited judicial exception into a practical application and instead amount to mere instructions to apply an exception and/or generally link the abstract idea to a particular field of use for the reasons discussed above, which do not provide integration.
Claim Rejections - 35 USC § 102
The rejection of claims 6-13, 15-16, and 20 under 35 U.S.C. 102(a)(1) as being anticipated by Cai et al. (2018) in the Office action mailed 24 March 2025 has been withdrawn in view of claim amendments received 24 Sept. 2025.
However, after further consideration a new grounds of rejection necessitated by Applicant’s claim amendment is set forth below under 35 U.S.C. 103.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 6-16, and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Cai (2018) in view of Robertson (2017). Any newly recited portion is necessitated by claim amendment.
Cited references:
Cai et al., Baseline correction for Raman spectra using penalized spline smoothing based on vector transformation, 2018, Anal. Methods, 10, pg. 3535-3533 and suppl (previously cited); and
Robertson et al. US 2017/0045455 A1; cited in IDS filed 29 Dec. 2021 (previously cited).
Regarding claims 1 and 8, Cai discloses a method for producing a baseline-corrected Raman spectrum (Abstract; Fig. 4), comprising the following steps:
Cai discloses (a) obtaining a baseline estimate on a Raman spectrum by fitting smoothing splines to the Raman spectrum (Figure 1; Figure 3; pg. 3527, col. 1, para. 1-3, e.g. spline smoothing on original Raman Spectrum).
Cai discloses (b) determining a difference in intensity values at a wavenumber, n, of the Raman spectrum compared to the baseline estimate (pg. 3527, col. 2, para. 1, e.g. eqn. 8, yb -yr).
Cai discloses (c) obtaining an updated baseline estimate by adjusting the intensity values of the baseline estimate where the spectral residual is larger than the estimated baseline (i.e. a positive difference), and other values are unchanged (pg. 3528, col. 1, para. 1-2, e.g. estimated baseline updated by comparing with spectral residual and corresponding intensities updated and vector elements set to 0).
Cai discloses (d) iterating by repeating the above steps on the updated spectral residual and vector v (i.e. the adjusted baseline estimates) (Figure 1).
Cai discloses (e) obtaining an optimal estimated baseline as the spectral residual of the final iteration by iterating the above steps (a)-(c) until a termination criterion is met, wherein the termination criterion is defined by the error between the estimated baseline and spectral residual between successive iterations falling below a threshold (i.e. a desired deviation between two consecutive adjusted baseline estimates is reached) (Figure 1; pg. 3527, col. 1, para. 1-2, e.g. d is a measure of the root mean square error, see eqns 8-11), such that an optimal estimated baseline is obtained (Figure 1).
Cai discloses placing knots for the smoothing spline to highlight regions where the estimated baseline and Raman Spectrum do not overlap (FIG. S8-S9, e.g. see knots=14).
Regarding claim 6, Cai discloses a method for producing a baseline-corrected Raman spectrum (Abstract; Fig. 4), comprising the following steps:
Cai discloses (a) applying an iterative fitting procedure on a Raman spectrum (FIG. 2, e.g. begins with original spectrum, and iterates until termination criterion is met; pg. 3526, col. 1, para. 3 to col. 2, para. 3; FIG. 3, e.g. see fitted curve at iterations.
Cai discloses (b) that in each iteration, evaluation parameters are calculated (FIG. 1), including calculating a distance between the estimated curve baseline and the spectral residual at each wavenumber (i.e. prediction errors) of the respective iteration (pg. 3527, col. 2, para. 1, e.g. yb-yr; pg. 3527, col. 1, para. 2, e.g. spectral residual is initial raman spectrum at first iteration). Cai discloses adjusting these distances (i.e. prediction errors) by taking a square root (i.e. a root transformation) of the errors (pg. 3527, col. 2, para. 1), and updating the estimated baselinel (i.e. the fitted baseline intensities) by setting intensity values of the spectral residual larger than the baseline estimate to the corresponding points of the estimated baseline to update the spectral residual and obtain a new baseline (i.e. form a new set of intensities), which demonstrates these negative differences are added to the intensity values to make them equal to the estimated baseline (pg. 3527, col. 2, para. 2, e.g. negative difference yb-yr if yr > yb; pg. 3528, col. 1, para. 1; pg. 3529, col. 1, para. 4).
Cai discloses (c) repeating the fitting of the splines on the updated spectral residual to obtain a new baseline estimate, and calculating prediction errors between the updated spectral residual and the new baseline estimate (Figure 1, e.g. process iterates for new spectral residual; pg. 3527,col. 1, para. 3 to col. 2, para. 1, e.g. iteration includes spline smoothing and error prediction).
Cai discloses (d) repeating this iterative fitting procedure until a termination criterion is met, wherein the termination criterion is defined by the error between the estimated baseline and spectral residual between successive iterations falling below a threshold (Figure 1; pg. 3527, col. 1, para. 1-2, e.g. d is a measure of the root mean square error, see eqns 8-11), such that an optimal estimated baseline is obtained (Figure 1).
Cai discloses placing knots for the smoothing spline to highlight regions where the estimated baseline and Raman Spectrum do not overlap (FIG. S8-S9, e.g. see knots=14).
Further regarding independent claims 1, 6, and 8 and dependent claims 2, 14 and 18, Cai does not disclose the following.
Regarding claims 1, 6, 8, and 18, Cai does not disclose performing node optimization on the transformed, baseline-corrected Raman spectrum by placing a selected number of nodes to highlight regions of the Raman spectrum in which one or more compound(s) of interest appears (claims 1, 6, and 8), wherein node optimization is performed in a manner to i) emphasize one or more peaks of interest, and ii) minimize other peak(s) (claims 1 and 6).
Further regarding claims 1, 6, and 8, Cai does not disclose analyzing the baseline-corrected Raman spectrum and determining that the sample is classified as being from a subject ii) who has kidney disease, and the extent of the disease state thereof. Cai further does not disclose administering dialysis treatment to the subject who has kidney disease based on the extent thereof, as recited in claims 1 and 8, or based on the extent of the disease state, administering subsequent dialysis treatment to the subject who has kidney disease by 1) increasing or decreasing the amount of time the subject is on the dialyzer, 2) increasing or decreasing the blood flow through the dialyzer, or 3) a combination of these, as recited in claim 6.
Regarding claim 2, Cai does not disclose the analyzing comprises one or more of principal component analysis (PCA), discriminant analysis of principal components (DAPC), partial least squares (PLS), and/or artificial neural networks (NN) to detect and/or quantify the condition.
Regarding claim 14, Cai does not disclose the Raman Spectrum is from a dialysate or urine sample.
However, the above limitations were known to one of ordinary skill in the art, before the effective filing date of the claimed invention, as shown by Robertson.
Regarding claims 1, 6, and 8, Robertson discloses a method for monitoring the health of dialysis patients with Raman spectroscopy (Abstract), which comprises analyzing a Raman spectrum to determine the disease state status of a patient by analyzing peak position (claim 1; Figure 3; [0134]; FIG. 13, e.g. peak position/height vs control), wherein the disease state is chronic kidney failure ([0116]) (i.e. kidney disease), as recited in claims 1 and 8. Robertson further discloses analyzing the Raman spectrum to determine various treatment outcomes or complications including end-stage renal disease (i.e. the extent of the disease state) ([0073]). Robertson further discloses the analysis of the Raman spectrum is used to identify critical health concerns and update treatment protocols comprising dialysis prescriptions ([0121]-[0122]; FIG. 3), wherein the dialysis prescriptions involve adjusting the prescription upwards to increase the frequency (i.e. increasing the amount of time the subject tis on the dialyzer) or intensity of dialysis (i.e. increasing blood flow) if the patient is deteriorating ([0022]).
Regarding claim 2, Robertson further discloses the analyzing to determine the disease state includes feeding the Raman Spectra into a statistical model, including a principal component analysis to identify the disease state ([0122]; FIG. 3-4).
Regarding claim 14, Robertson further discloses the Raman spectrum of the patient is from a dialysate sample (claim 38; [0162]).
Regarding claims 1, 6, 8, and 18, Robertson further discloses performing a peak analysis of the Raman spectrum to identify specific peaks of interest (i.e. a node optimization to emphasize one or more peaks of interest and minimize other peaks), and placing arrows to emphasize a peak in the Raman spectrum indicative of a compound of interest related to the condition ([0134], e.g. identify peaks of interest] [0137]; FIG. 13, e.g. see “glucose…” peak highlight for patient sample relative to control).
Last, Robertson further discloses that patients who undergo dialysis are at risk of death ([0013]), and the method of assessing healthy of dialysis patients solves a need for methods that improve the health assessment of dialysis patients and improves individual patient care ([0033]-[0034]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Cai, to have analyzed a Raman spectrum of a dialysate sample using PCA to detect the presence of kidney disease and the extent of the disease state thereof by analyzing the Raman spectrum to highlight regions with a compound of interest and administering the dialysis treatment to the subject with kidney disease based on the extent of the kidney disease, by increasing the frequency or intensity of the dialysis according to the method of Robertson discussed above, thus arriving at the inventions of claims 1-2, 6, 8, and 14. One of ordinary skill in the art would have been motivated to combine the methods of Cai and Robertson in to improve the health assessment of dialysis patients who are at risk of death, thus improving patient care, as shown by Robertson ([0013];[0033]-[0034]). This modification would have had a reasonable expectation of success because Cai produces a baseline-corrected Raman Spectrum and Robertson analyzes Raman spectrum to determine a disease, such that the analysis method of Robertson is applicable to the Raman spectrum of Cai.
While Cai in view of Robertson does not explicitly a number of nodes are placed to highlight the compound of interest as recited in claim 19, Robertson does place arrows to emphasize the regions where the compound of interest appears. However, the placement of nodes is interpreted as a matter of design choice, and Applicant has not disclosed that this feature provides an advantage, is used for a particular purpose, or solves a stated problem when compared to placing arrows as shown by Robertson. Therefore, the placement of arrows shown by Robertson would perform equally as well in emphasizing regions of the Raman spectrum in which a compound of interest appears and such a modification fails to patentably distinguish over Cai in view of Robertson.
Regarding claim 3, Cai in view of Robertson disclose analyzing the Raman spectrum to determine the subject has kidney disease, as applied to claim 1 above. The embodiment in which the subject is determined to have bladder cancer is not required by the claims, and thus the limitations further limiting how the subject is determined to have bladder cancer is not required by the claim as discussed in claim interpretation above. Therefore, claim 3 is rejected for the same reasons discussed above for claim 1.
Regarding claim 7¸ Cai further discloses adjusting intensity values of the fitted baseline intensities when the spectral residual is larger than the estimated baseline (i.e. a positive difference), and where the spectral residual are less than the estimated baseline, intensity values are unchanged (pg. 3528, col. 1, para. 1; pg. 3529, col. 1, para. 3).
Regarding claim 8, Cai discloses a method for producing a baseline-corrected Raman spectrum (Abstract; Fig. 4), comprising the following steps:
Cai discloses (a) obtaining a baseline estimate on a Raman spectrum by fitting smoothing splines to the Raman spectrum (Figure 1; Figure 3; pg. 3527, col. 1, para. 1-3, e.g. spline smoothing on original Raman Spectrum).
Cai discloses (b) determining a difference in intensity values at a wavenumber, n, of the Raman spectrum compared to the baseline estimate (pg. 3527, col. 2, para. 1, e.g. eqn. 8, yb -yr).
Cai discloses (c) obtaining an updated baseline estimate by adjusting the intensity values of the baseline estimate where the spectral residual is larger than the estimated baseline (i.e. a positive difference), and other values are unchanged (pg. 3528, col. 1, para. 1-2, e.g. estimated baseline updated by comparing with spectral residual and corresponding intensities updated and vector elements set to 0).
Cai discloses (d) iterating by repeating the above steps on the updated spectral residual and vector v (i.e. the adjusted baseline estimates) (Figure 1).
Cai discloses obtaining an optimal estimated baseline as the spectral residual of the final iteration by iterating the above steps (a)-(c) until a termination criterion is met, wherein the termination criterion is defined by the error between the estimated baseline and spectral residual between successive iterations falling below a threshold (i.e. a desired deviation between two consecutive adjusted baseline estimates is reached) (Figure 1; pg. 3527, col. 1, para. 1-2, e.g. d is a measure of the root mean square error, see eqns 8-11), such that an optimal estimated baseline is obtained (Figure 1).
Regarding claim 9¸ Cai further discloses intensity values are unchanged where the spectral residual is less than the estimated baseline (i.e. a zero or negative difference is determined) (pg. 3528, col. 1, para. 1-2, e.g. estimated baseline updated by comparing with spectral residual and corresponding intensities updated and vector elements set to 0), as discussed above for claim 8. Because the claims do not require that a positive difference is determined, the claims do not require a step of adjusting the intensity values under the broadest reasonable interpretation of the claims as discussed in claim interpretation above.
Regarding claim 10¸ Cai further discloses the iterating (d) is repeated until a termination criterion is met (Figure 1), wherein the termination criterion is defined by a convergence of d below a threshold 10-4 (i.e. a selected convergence criterion ε) (pg. 3527, col. 2, para. 2).
Regarding claim 11, Cai further discloses the termination criterion is 10-4, which is within the claim range of 0.0001 to 10 and thus anticipates the claimed range (pg. 3527, col. 2, para. 2). See MPEP 2131.01 I.
Regarding claim 12, Cai further discloses an example in which the number of knots selected is 14 or 20 (Suppl. FIG. S8).
Regarding claim 13¸ Cai further discloses applying the method to Raman spectra of a complex mineral sample (i.e. obtained from a solid) (pg. 3532, col. 1, para. 3) or various oils (i.e. liquid) (pg. 3532, col. 2, para. 2).
Regarding claim 15¸ Cai further discloses step (a) includes obtaining an initial baseline estimate from the original Raman Spectrum (pg. 3527, col. 1, para. 2-3, e.g. original Raman spectrum is initial spectral residual; Fig. 3), and that the deviation of the estimated baseline from the initial spectral residual (i.e. the observed raw spectral intensity) is yb-yr.
Cai discloses (b), the intensity values are unchanged where the spectral residual is less than the estimated baseline (i.e. areas with zero or negative intensity deviations remain the same) (pg. 3528, col. 1, para. 1-2, e.g. estimated baseline updated by comparing with spectral residual and corresponding intensities updated and vector elements set to 0), as discussed above for claim 8. Because the claims do not require that a positive difference is determined, the claims do not require a step of adjusting the intensity values according to yi(new) under the broadest reasonable interpretation of the claims as discussed in claim interpretation above.
Cai discloses (c) feeding the updated spectral residual (i.e. the new intensities) in a new iteration to get a second estimate of the baseline, and thus updated baseline intensities (Figure 1).
Cai discloses (d) iterating the above steps (a)-(c) until a termination criterion is met, wherein the termination criterion is defined by the error between the estimated baseline and spectral residual between successive iterations falling below a threshold (i.e. a difference between two consecutive baseline fits is small) (Figure 1; pg. 3527, col. 1, para. 1-2, e.g. d is a measure of the root mean square error, see eqns 8-11).
Regarding claim 16¸ Cai further discloses the Raman spectra is mathematically modeled as y(t) = s(t) + b(t) + n(t), where ys(t) is the pure spectral data (i.e.. peak intensities, a), b(t) is the simulated baseline data (i.e. unknown true baseline intensities), and n(t) is random noise, which are vectors with values for each time/wavenumber t (pg. 3529, col. 1, para. 1).
Regarding claim 19, Cai discloses placing knots (i.e. nodes) for the smoothing spline to highlight regions where the estimated baseline and Raman Spectrum do not overlap (FIG. S8-S9, e.g. see knots=14).
Regarding claim 20, Cai discloses placing knots for the smoothing spline to highlight regions where the estimated baseline and Raman Spectrum do not overlap (FIG. S8-S9, e.g. see knots=14).
Therefore, the invention is prima facie obvious.
Response to Arguments
Applicant's arguments filed 24 Sept. 2025 regarding 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicant remarks that the Examiner has not shown how the prior art teaches the feature of “performing node optimization…” as recited in amended claim 1, and remarks that Cai’s spline fitting method requires the appropriate selection of the interpolation node which is dependent on the researcher’s experience and is affected by noise, and in contrast the claimed invention provides specific node sets for the selected diseases chosen to specifically highlight regions of the Raman spectrum in which one or more compound(s) of interest appears and/or highlight one or more regions where the Raman spectrum and baseline do not overlap, and as the node placement is determined by the disease of interest, the method would not be subject to the same drawbacks resulting in a more precise disease state determination (Applicant’s remarks at pg. 30, para. 3 to pg. 31, para. 2). Applicant further remarks the claimed method corrects for “baseline overload” by excluding wavenumber peaks that overwhelm less prominent areas of the Raman spectrum, and that nodes are defined points along a Raman spectrum at specific wavenumbers and the method involves fitting a cubic spline through the spectral data so that it intersects with all these nodes and that when the locations of the nodes are changed, different parts of the spectrum are retained (Applicant’s remarks at pg. 31, para. 2 to pg. 32, para. 2).
This argument is not persuasive. Overall, Applicant’s arguments are not commensurate with the scope of the claims. First, the performed node optimization in claim 1 does not require anything related to a specific disease of interest as currently recited. Second, the claims do not require defining nodes at specific wavenumbers, fitting a cubic spline through the spectral data so it intersects with the nodes, and changing locations of nodes.
Furthermore, the arguments do not take into account Robertson. Claim 1 only broadly requires “performing node optimization on the baseline-corrected Raman spectrum, wherein the node optimization is performed in a manner to i) emphasize one or more peaks of interest, and ii) minimize other peak(s); and comprises placing a selected number of nodes to…ii) highlight one or more regions where the Raman spectrum and the baseline do not overlap”. As discussed in the above rejection, Robertson further discloses performing a peak analysis of the Raman spectrum to identify specific peaks of interest, thus de-emphasizing other peaks (i.e. a node optimization to emphasize one or more peaks of interest and minimize other peaks), and placing arrows to emphasize a peak in the Raman spectrum indicative of a compound of interest related to the condition ([0134], e.g. identify peaks of interest] [0137]; FIG. 13, e.g. see “glucose…” peak highlight for patient sample relative to control). Furthermore placing of nodes versus arrows is interpreted as a matter of design choice as applied in the above rejection. The claims do not require anything other then “emphasizing one or more peaks and minimize other peaks, and placing nodes to highlight regions of the Raman spectrum corresponding to a compound of interest. If Applicant intends for the node optimization of the claims to specifically involve fitting splines to nodes corresponding to a particular condition, the claims should be amended to recite details on how the node optimization is performed.
Double Patenting
The provisional rejection of claims 4-5 and 17 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-7, 11, 13-22, and 26-27 of copending Application No. 17/146,301 in view of Cai (2018) in the Office action mailed 24 March 2025 has been withdrawn in view of the cancellation of these claims received 24 Sept. 2025.
The provisional rejection of claims 1-3 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-7, 11, 13-22, and 26-27 of copending Application No. 17/146,301 in view of Cai (2018) in the Office action mailed 24 March 2025 has been withdrawn in view of the terminal disclaimer filed and approved 02 July 2025 in the reference Application 17/146,301.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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