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 .
Detailed Action
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/20/2026 has been entered.
Summary
This is the Final Office Action based on application 16/978959 RCE response filed 08/17/2026.
Claims 1, 4 & 6 and fully considered.
Claims 2-3, 5 & 17 are cancelled.
Claims 7-16 are withdrawn.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition ofmatter, or any new and useful improvement thereof, may obtain a patent therefor, subject to theconditions and requirements of this title.
The claimed invention of Claims 1, 4, 6, & 17 are rejected under 101 as they are directed to non-statutory subject matter.
The invention of instant claims is drawn towards a method of detecting a neurodegenerative condition selected from the group of FTLD, and ALS. However, as instantly considered as a whole the claim is drawn towards the judicial exceptions which are a combination of a natural correlation and abstract idea without significantly more to make the claims move past these judicial exceptions.
Through 101, inquiry:
Inquiry: Is the claim directed to a statutory category of invention?
Yes, the claims including and depending on independent claim 1 are drawn towards a statutory category (a method).
Step 2A, Prong 1: Does the claim involve a Judicial Exception?
Independent claim 1 and those that depend therefrom are directed to and heavily revolve around the calculation and “using,” and “determining,” of a of “DO value” formula/equation, which is calculation of this DO value. As instantly clamed- “calculating,” which includes the claimed using and determining of the DO value, including the claimed integration formula/equation for the DO value is an abstract idea/mental process/math as instantly claimed which can be performed by the human mind. This is especially since the claimed integration is one simple enough to do in the human mind.
The claim also is directed to a natural correlation, which is a law of nature judicial exception. The -- “detecting a neurodegenerative disease,” which is FTLD or ALS, and is a natural correlation of the level of MARCKS phosphorylated at position 46 and the level of non-phosphorylated MARCKS and their correlation/association with ALS and FTLD. Even though the word “diagnosing,” is not use, that is what is being done in the instant claims, and the natural correlation (disease diagnosis of neurodegenerative disease correlation with the DO/measured pSer46 and MARCKS measured amounts, is still implicitly in the claim).
Even further, the claimed “comparing,” comparison of the calculated DO value to a DO cutoff value to see if its above or below the cutoff value to then “Detect,”/diagnose FTLD or ALS is also recitation of a judicial exception since this is a mental process, which is an abstract idea.
See MPEP 2106.04 (a) & 2106.04 (b).
Step 2A, Prong: Has the abstract idea or natural correlation been integrated into a particular practical application?
In Claim 1, there is no particular practical application and the answer is no.
In addition to the claimed judicial exceptions the additional steps are required:
Preparing a sample comprising CSF and a buffer comprising Tris-HCL, SDS, DTT, wherein the preparing comprises denaturing proteins in the sample by heating the sample;
Measuring the pSer46 MARCKS and non- phosphorylated MARCKS by liquid chromatography-tandem mass spectrometry.
It is noted that no steps occur in the claim where the judicial exceptions are used, after the judicial exceptions are performed. Therefore, there is no practical application after DO is calculated, compared and FTLD or ALS is detected/diagnosed.
For step i), the use of a buffer comprising Tris-HCL, SDS, and DTT is
insignificant extra solution activity and therefore does not integrate the judicial exception into a practical application. Buffers, as instantly claimed and in general are compounds or solutions that help maintain a stable pH level by neutralizing added acids or bases, crucial for biological systems like blood. Buffers are not meant to react, so there is no derivatization of the CSF that happens with a buffer, especially as generally claimed. Also, “denaturing proteins in the sample by heating the sample,” also does nothing to practically apply and is something that can/could happen naturally if said proteins are left in a heated room. Therefore, as generally claimed, both of these things are considered extra-solution activity and do nothing to practically apply the claimed judicial exceptions. See MPEP 2106.04 (d) I. & MPEP 2106.05 (g).
For step ii)—liquid chromatography- tandem mass spectrometry is used merely to gather data in conjunction with/for the claimed law of nature and abstract idea. Therefore, this does not practically apply the judicial exceptions. Data gathered/gathering to use the judicial exception is considered extra-solution activity and therefore does not practically apply. See MPEP 2106.05 (g).
Therefore, particularly at the level of generality claimed—there is not integration into a practical application.
Step 2B: Do the claims recite any elements which are significantly more than the abstract idea or natural correlation?
In addition to the claimed judicial exceptions the additional steps are required:
Preparing a sample comprising CSF and a buffer comprising Tris-HCL, SDS, DTT, wherein the preparing comprises denaturing proteins in the sample by heating the sample;
Measuring the pSer46 and MARCKS by liquid chromatography-tandem mass spectrometry
For step i), the use of a buffer comprising Tris-HCL, SDS, and DTT use as a buffer is well understood, routine and conventional (WURC). Buffers main functions are to resist changes in pH and maintain a stable environment for analytes when analyzed. This also applies to the claims, preparing comprising denaturing proteins in the sample by heating the sample as this is something that can happen naturally if a sample is left out in the open on a hot day. Therefore, as claimed, this is WURC. Therefore, both of these things are standard laboratory technique and are not sufficient to show an improvement in technology or add significantly more. See MPEP 2106.05 (a) & MPEP 2106.05 (d).
For step ii) measuring pSer46 and MARCKs by liquid chromatography tandem mass spectrometry, is just measurement by a WURC laboratory technique, and therefor is not enough to be significantly more. MPEP 2106.05 (d).
That steps i) and ii) above are WURC in the art is evidenced by
PIKE in US 20180067133.
PIKE teaches that the biomarkers detected can be in phosphorylated form (paragraph 0064) and of detection by tandem mass spectrometry (paragraph 0044, 0051, 0074, 0400) and also of using liquid chromatography (paragraph 0334) and CSF denaturation as claimed (paragraph 0335). PIKE also teaches that the biomarkers detected can be in phosphorylated form (paragraph 0064) and of detection by tandem mass spectrometry (paragraph 0044, 0051, 0074, 0400) and also of using liquid chromatography (paragraph 0334). PIKE also teaches of processing the CSF samples by denaturation (paragraph 0356) and,
FUJITA in “HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer’s disease”
FUJITA teaches of detection by liquid chromatography (LC) in combination with tandem mass spectrometry(MS/MS)(Page 13, paragraph 2, Page 2, Figure 1 description, Page 5, first paragraph). FUJITA teaches that the sample is mixed with Tris-HCl and SDS and DTT (Page 10, last paragraph, lines 1-4 & 7 lines from bottom).
Though part of the claimed judicial exception the examiner also notes that the claimed formula for DO is a Euclidean distance/distance from origin calculation. This a routine calculation and known formula, which is shown by the prior art below, and is used to determine the distance between two points.
Therefore, the claimed measurement of protein markers in CSF by the claimed methods, especially at the level of generality claimed is well understood, routine and conventional method for measurement in the art, and therefore this is not considered significantly more than the claimed judicial exceptions. See MPEP 2106.05 (d).
So, particularly at the level of generality claimed—this is not considered significantly more than the claimed judicial exceptions, nor is it considered an improvement in the technological field.
The dependent claims are reviewed as was the independent claim above.
Claim 4, specifies that numerical values are normalized. This is a type of mathematical manipulation so is part of the claimed judicial exception/abstract idea and one that is routine in the art, so does not change any of the matters above.
Claim 6, specifies what the DO cutoff value is. This also doesn’t change anything, because is part of the natural correlation.
Claim Objections
Claim 1 is objected to because of the following informalities:
With respect to Claim 1, in the equation in Claim 1, “pSer46-MARCKS,” and “non-phosphorylated MARCKS,” are recited, however above in the claim “pSer 46,” is not indicated like this. Though it is clear in the equation what compound is what, applicant should specify any abbreviations used by the full written out compound name.
Appropriate correction is required.
Claim Rejections - 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 non-obviousness.
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, 4 & 6 are rejected under 35 U.S.C. 103 as being unpatentable over PIKE in US 20180067133 in view of FUJITA in “HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer’s disease” (as cited on IDS dated 09/08/2020) in view of HU in Assessment of gene order computing methods for Alzheimer’s disease, and further in view of SCIENCING in How to Find Euclidean Distance.
With respect to Claims 1, PIKE teaches of a method for detection of alzheimer’s disease and alzheimer’s disease with fronto-temporal dementia (FTLD) combination (abstract, paragraph 0031, 0186). PIKE further teaches of detecting MARCKs- related proteins for this detection (paragraph 0018, 0060, 0149-0150, 0156, Table 1) and of determining/comparing if the measured biomarker is increased in relation to a reference/control (paragraph 0070-0071, 0019-0027). PIKE also teaches that the biomarkers detected can be in phosphorylated form (paragraph 0064) and of detection by tandem mass spectrometry (paragraph 0044, 0051, 0074, 0400) and also of using liquid chromatography (paragraph 0334).
PIKE also teaches of processing the CSF samples by denaturation (paragraph 0356), and also of heating to 55 degrees Celsius from room temperature (25 degrees Celsius) (paragraph 0356).
PIKE does not teach of the detection of pSer46-MARCKS detection or of processing with the claimed specific buffer solution.
FUJITA is used to remedy this and more specifically teach of detecting a serine residue at position 46 of MARCKS is phosphorylated in Alzheimer’s Disease patients. Specifically, FUJITA teaches that HMGB1 triggers Ser46-phosphorylation of MARCKS, which is the protein that regulates stability in the actin network--- and that this phosphorylation at position 46 is sustained throughout Alzheimer’s disease. FUJITA further teaches that HMGB1 triggers the specific Ser46 phosphorylation of MARCKS (Abstract). FUJITA et al. teach of detecting/measuring Ser46-phosphorylated MARCKS signals--- after addition of HMGB1, by detecting HMGB1 in a sample prepared from CSF specimen/sample (Page 6, Figure 4, description (f) &(g), Page 7, second paragraph, page 12, 3rd paragraph from bottom). FUJITA also teaches of detection by liquid chromatography (LC) in combination with tandem mass spectrometry(MS/MS)(Page 13, paragraph 2, Page 2, Figure 1 description, Page 5, first paragraph). FUJITA further teaches of comparison, “comparing,” to the phosphoproteome quantities to those of a control sample (Page 10, 2nd from last paragraph and 6 lines from bottom and down in that paragraph). FUJITA teaches that the sample is mixed with Tris-HCl and SDS and DTT (Page 10, last paragraph, lines 1-4 & 7 lines from bottom).
FUJITA et al. further teach of detecting disease and other neurodegenerative diseases by looking for/detecting phosphorylation of MARCKS, a submembrane protein that regulates the stability of the actin network that occurs at Ser46 (MARCKS protein phosphorylated at position 46) prior to aggregation of Aβ and is sustained throughout the course of AD in human (abstract, also see Figure 1, 2, and page 7, first paragraph). FUJITA et al. further teach of detecting/ measuring non- phosphorylated MARCKS molecules (Page 4, Figure 3 & Figure 3 description).
FUJITA teaches that the measurements are compared to that of a healthy control and that if there is an increase compared to healthy control that is indicative of disease (Page 6, second paragraph, line 2 and lines 1-5, and Page 10, paragraph 6, 2 & 5 lines from bottom) (which makes the instantly claimed calculation of DO compared to healthy control obvious since the DO is just a calculation from the claimed measurements).
FUJITA et al. further teach of using statistics to perform analysis of the phopspho-proteome.
Specifically, FUJITA teach that peptide ratios followed log-normal distribution. For biological analyses, the data were considered to follow a normal distribution and are represented as the mean± standard error. Student’s t-test was applied for two group comparisons. Further, non-parametric Wilcoxon’s rank-sum test was employed for this analysis. (Page 13, last paragraph, page 14, first paragraph).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to detect pSer46 MARCKs and non-phosphorylated versions as is done in the method of FUJITA for detection of Alzheimer’s disease in the method of PIKE for detecting Alzheimer’s with fronto-temporal dementia disease due to the advantage MARCKs phosphorylation at Ser46 show for being a hallmark of neurite degeneration (Page 2, title of bottom paragraph & bottom paragraph). Further, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to use the buffer of FUJITA in the method of PIKE due to the advantage the three part buffer of Tri-HCl, SDS, and DTT as a lysis buffer to assisting in sample lysis operations (FUJITA, page 10, last paragraph).
With respect to the instantly claimed formula 1, FUJITA et al. does not teach of this. In the instant claims and in applicant’s instant specification PGPUB paragraph 0183 it is shown that DO in the formula stands for “distance from origin,” --- In applicants instant PGPub, they also teach that Wilcoxon test is also used (see paragraph 0183 of instant PGPub).
FUJITA does not call out the specifically claimed DO formula and the method including a step for calculating the DO value specified by formula 1 of claim 1—which as claimed is a Euclidean distance formula.
HU et al. is used to remedy this and teaches of a method for assessment of genes in Alzheimer’s disease using computational genetics (abstract). Specifically, HU uses different distance formulas including Euclidean distance, squared Euclidean distance, and Pearson distance to analyze the Alzheimer’s markers (abstract, methods). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to use Euclidean distance analyses as is done in HU in the methods of FUJITA and PIKE to analyze the MARCKS phosphorylated pos 46 markers and the non phosphorylated markers, due to the advantage that these analyses are known to have superiority when data is not normalized (HU, abstract, conclusion, page 6, second column, 2nd-last paragraph).
If it is not clear to one of ordinary skill in the art that what is claimed in the instant invention is Euclidean distance, SCIECING is used to remedy this.
SCIENCING et al. teach the Euclidean distance refers to the distance between two points in space (Page 1, first paragraph, Page 2, first paragraph). SCIENCING et al. further teach that to calculate the Euclidean distance in two- dimensional space (Such as on a graph with x and y axes to mark to variables), the difference in the x coordinates (on variable on graph, which could be the phosphorylated MARCKS), and the calculating the difference in the y coordinates (could be the non- phosphorylated variable), and then take the square root of the sum to find the distance (Page 3). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to calculate the calculate the Euclidean distance as is done in in HU and SCIENCING in the method of FUJITA and PIKE due to the advantage this offers in finding the distance or difference between two points or variables (even ones including multiple points) (Sciencing, paragraph 1).
Further as the DO value is made obvious as shown above, and as both pSer46-MARCKS and non-phosphorylated MARCKS are taught as shown above as being found detected and comparing/ comparison to a control for diagnosing/detecting FTLD and neurodegenerative diseases, though the prior art does not call out specifically comparing a DO value specifically to a reference/control or cutoff value as this value is based on the compounds pSer46-MARCKS and non-phosphorylated MARCKS which are taught in comparison or control, this makes it obvious to one of ordinary skill in the art to also compare a DO value to a cutoff/reference or control since DO /Euclidean distance calculations are shown to have advantages as already shown in the reasons for combination above from HU and Sciencing.
With respect to Claim 4, HU et al. teach that if vector components are normalized that one must pay attention to which distance calculation they use an weigh issues/concerns (Page 6, column 2, last paragraph and Page 7, column 1, first paragraph).
With respect to Claim 6, FUJITA et al. teach of comparison to compared control/cutoff values (Page 10, proteome analysis). FUJITA teaches that the measurements are to that of a healthy control and that if there is an increase compared to healthy control that is indicative of disease (Page 6, second paragraph, line 2 and lines 1-5, and Page 10, paragraph 6, 2 & 5 lines from bottom) (which makes the instantly claimed calculation of DO compared to healthy control obvious since the DO is just a calculation from the claimed measurements). HU et al. also teaches of comparison to control samples (Page 6, column 1, paragraph 4, Figure 1) and that the controls are for control (which can be interpreted as healthy), incipient, moderate, and severe data (Page 6, column 1, paragraph 1). Since severe is one data, the control can be interpreted as not affected by disease or healthy It could have been obvious to adjust the cutoff value dependent on the analysis performed.
Response to Arguments
Applicant's arguments filed 08/17/2026 have been fully considered but they are not persuasive.
Applicant argues with respect to the 101 rejection. The 101 rejection is maintained for the amended claims as shown in the above rejection. As the claims were significantly amended, the examiners response to these amendments is found and can be reviewed in the rejection and is not repeated in full here.
Applicant argues that the recitation of LC-MS/MS is employed in the instant claimed “to more accurately measure phosphorylated Ser46-MARCKS,” and the unphosphorylated claimed compound. The examiner notes that while this might be the case, LC-MS/MS is still found to be WURC. It does not practically apply the claims in light of what is meant by that with respect to subject matter eligibility, nor does it add significantly more as is WURC.
Applicant further argues that the claimed “detecting,” and “formula 1.” Is not a naturally occurring phenomena. With respect to this, applicant should review the 101 rejection. What was said is that the claim is a combination of a natural correlation and abstract idea judicial exceptions. The formula itself is a mathematical equation and is a judicial exception. Applicant further argues that the “DO,” claimed is a “human created analytical parameter.” With respect to this, the examiner notes that it is in fact an equation, which again is an abstract idea judicial exception.
Applicant argues that the claims recite physical steps that cannot be performed by the human mind. These steps include measuring by LC-MS/MS, the addition of the claimed buffer and newly claimed denaturing of proteins by heat. While the examiner agrees that the addition of the buffer and mass spectrometry cannot be performed in the human mind, and that denaturing by heat “can,” be a physical step, the examiner reminds applicant that whether or not something is solely performed in the human mind or not is not the test for 101 and the examiner never said that these steps were performed in the mind.
The examiner has noted the steps in the 101 rejection, which are considered to be abstract ideas and that can, as claimed be performed in the human mind or that are drawn to math or mental processes without then practically applying these steps/results, nor without adding anything significantly more. The buffer addition, heating, and mass spectrometry steps are not performed in the human mind. The examiner agrees on this, however the examiner does not agree that these steps make the instant claims eligible, since they do not practically apply nor do they add significantly more to the claimed judicial exceptions. The reasons for this are shown in the above rejection.
It is also noted that as claimed--- the claimed three-part buffer does not seem to “transform,” the sample as no derivatization or binding, nor the resulting compound thereof is claimed. Applicant argues that transformation occurs, but there is not any transformation as claimed. Therefore, if any transformation occurs, in the least, it is not clearly claimed.
Applicant further argues with respect to MPEP 2106.05 (c ) that the claimed steps transforms the claimed article “ to a different state or thing.” The examiner again, disagrees with applicant. If any transformation is present, it is not claimed, and it is certainly not claimed in a way which practically applies nor which adds significantly more to the claimed judicial exceptions.
Applicant further argues that the claimed buffer and heating steps are not insignificant extra solution activity and that denaturation is claimed as the transformation. Applicant further argues that the recited buffer and heating components are not present to maintain pH and that they are instead a reducing agent, an anionic detergent that unfolds and coats the polypeptides, and then the claimed heating completes the loss of native structure. Well, with respect to this, if this is the case, then applicant should claim it as only a “buffer,” and “heating,” to “denature” is claimed and nothing additional is claimed about unfolding and coating or cleaving disulfide bonds is claimed and buffers, as actually claimed, are in fact, not meant to react. Therefore, applicants arguments are not commensurate in scope with the claims and further—therefore there is no transformation claimed.
Applicant even further argues that Claim 1 also provides an improvement technology or a technological field. Applicant notes that the claimed pSer-MARCKS alone is not a workable diagnostic biomarker, having low sensitivity for FTLD and ALS. Applicant further states that by using this biomarker in combination with the non-phosphorylated marker in the claimed DO value, the method achieves a much higher sensitivity of 0.857 for FTLD and 1.00 for ALS, with a specificity of .8000. With respect to this, this is currently not convincing as what applicant seems to be arguing is the improvement is another calculated numerical value (so another abstract idea). Further, as claimed, there is nothing about claimed about sensitivity or specificity. Though this is a Final rejection, if applicant submits and SME Declaration with respect to these points when filing and RCE and if applicant’s representative can find any cases/case law where this type of argument has been successful for specifically diagnostic type claims, the examiner would be interested to see it and would be willing to consider it. Note- the examiner is not given time to consider SME Declarations after-final.
Therefore, all examined claims remain rejected under 101.
With respect to the 103 rejection, applicant argues that PIKE does not teach of suggest measuring MARCKS at all and instead it teaches of only MARCKS related protein. Applicant argues that the protein taught in PIKE has a different SEQ NO than what is claimed and overall is a different compound. With respect to this, the examiner notes that with respect to how protein the proteins are claimed MARCKS-related protein reads on and includes the claimed MARCKS protein and therefore makes it obvious. If applicant means something more specific, then they should claim it.
Applicant also argues that PIKE does not teach of FTLD or ALS and instead focuses on Alzheimers. The examiner disagrees. PIKE specifically teaches that the methods taught therein can also help diagnose fronto-temporal (lobe) dementia, as claimed (paragraph 0007, 0031, 0084).
Applicant further argues that PIKE does not teach of the claimed sample preparation. While the examiner does agree that PIKE does not teach of the claimed buffer, this is why in fact that the FUJITA reference was used. The examiner maintains that PIKE teaches of the claimed heating, as shown in the above rejection.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
With respect to FUJITA, applicant argues that they do not cure any purported deficiencies of PIKE. The examiner disagrees.
Applicant further argues that the FUJITA reference does not teach of detecting an increase in the MARCKS protein as an indicator for disease. With respect to this, the examiner points out that the PIKE further teaches of detecting MARCKs- related proteins for this detection (paragraph 0018, 0060, 0149-0150, 0156, Table 1) and of determining if the measured biomarker is increased in relation to a reference/control (paragraph 0070-0071). Therefore, FUJITA does in fact teaches of the pSer46-MARCKS detection, with good reason for combination with PIKE.
Applicant further argues that HU and Sciencing also do not cure any of the purported deficiencies of the other references and that the generic teaching of Sciencing and HU to these points do not teach of the claimed computing of the distance from the coordinate origin to a single point whose coordinates are the two measured MARCKS proteins and therefore forming a single integrated diagnostic parameter. With respect to this, as what applicant seems to be claiming is all diagnoses (detection of biomarkers and association with disease) and math (the equation and comparisons), the examiner disagrees that the used generic teaching of the prior art does not teach of this and instead maintains that it makes the instant invention obvious. If there is more to what is claimed than this diagnosis and math, then it is suggested that applicant claim it. Further, though the examiner is not sure if it would help, applicant could consider filing a SME Declaration where applicant shows along with appropriate claim amendments how there is more than mathematical calculations and diagnoses going on in the claims, and exactly how the purported “technological improvement,” was accomplished and is performed.
Applicant further again argues with respect to “Exhibit A,” which they have submitted with this action. Though the examiner has reviewed the reference in Exhibit A, it is not found to be convincing with respect to overcoming FUJITA. This is due to the inclusion now of the PIKE reference in the rejection above. Due to what is shown in the PIKE reference, the examiner disagrees with applicant’s argument that “one would not envisage changes in MARCKS levels of FTLD and ALS patients would resemble those of AD patients.” Again, as shown above, PIKE does in fact teach of detecting both fronto-temporal lobe dementia and alzheimer’s together, using MARCKS protein.
All elected claims remain rejected.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Sarah Folkesson Hansson in, “Validation of a prefractionation method followed by two-dimensional electrophoresis – Applied to cerebrospinal fluid proteins from frontotemporal dementia patients.”
FOKELSSON teaches of a prefractionation method followed by analysis for detecting Alzheimer’s in CSF samples (abstract). FOKELSSON teaches that CSFT samples and used and DTT is used (Page 8, column 2, paragraph 5), DTT with Tris and SDS is used (page 9, column 1, first paragraph), or DTT, Tris-HCL, and SDS can be used together (Page 9, column 1, second paragraph). This/these buffers offer advantage for allowing prefractionation (Page 8, column 2, 2nd to last paragraph).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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