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
Summary
This is the Non-Final Office action based on the 18/043181 election filed 03/09/2026.
Claims 1-6, 14, 16 & 19-22 are elected and pending.
Claims 13, 15, 18 & 23-24 are cancelled.
Claim 7-12, 17 & 25 are withdrawn.
Election/Restriction
Applicant’s election without traverse of Claims 1-12, 14, 16-17 & 19-22 and the species of lysine which is identified in the parent PCT application at page 25 (i.e. the first four chemical shift ranges specified in Claim 1: 1.37-1.55 ppm, 1.65-1.75 ppm, 1.83-1.94 ppm, and/or 3.00-3.05ppm in the reply filed on 03/09/2026 is acknowledged.
The examiner notes however, that applicant elected the species of “lysine,” which has the chemical shift ranges of 1.37-1.55 ppm, 1.65-1.75 ppm, 1.83-1.94 ppm, and/or 3.00-3.05ppm. Therefore, the claims that are specific to biomarkers other than lysine or chemical shift shifts other than 1.37-1.55 ppm, 1.65-1.75 ppm, 1.83-1.94 ppm, and/or 3.00-3.05ppm are drawn towards the unelected species.
Therefore, only claims 1-6, 14, 16 & 19-22 have been examined as this group properly reflects the elected claims/species combination.
Claims 25 and the non-elected specie, which from the examiner review also includes Claims 7-12 and 17 as they are drawn towards other biomarkers and chemical shifts than the elected ones are drawn towards the unelected species so they are also withdrawn from prosecution pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/09/2026.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 4 & 14 and any claims which depend therefrom are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
With respect to Claim 3, it includes a limitation in parentheses, and also use of “preferably.” Both of these things make it unclear if what is in parentheses is required or if it is instead optional. Therefore, this claim is unclear.
With respect to Claim 4, it includes a limitation in parentheses, and also use of “preferably.” Both of these things make it unclear if what is in parentheses is required or if it is instead optional. Therefore, this claim is unclear.
With respect to Claim 14, it includes the use of “preferably.” This makes it unclear if this is required or if it is instead optional. Therefore, this claim is unclear.
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 1-6, 14, 16 & 19-22 are directed to non-statutory subject matter.
The invention of instant claims is drawn towards a method for “confirming,” if a patient has a multiple sclerosis relapse or prognosis of a relapse, or a patient’s response to therapy.
Through 101, inquiry:
Step 1: Is the claim directed to a statutory category of invention?
Yes, the claims are drawn towards a statutory category (a method).
Step 2A, Prong 1: Do the claims involve a Judicial Exception?
Independent claim 1 and those that depend therefrom involve the judicial exception of a law of nature which is a natural correlation. The natural correlation in the claims is the correlation of lysine or other biomarker claimed, it’s H-NMR chemical shift and their association with if the patient has a prognosis of MS, a relapse, or will have response to therapy.
Further as claimed, “comparing,” to a reference or standard and “confirming,” as claimed are mental processes which are abstract ideas and also judicial exceptions.
Step 2A, Prong: Has the natural correlation or abstract idea been integrated into a particular practical application?
For Claim 1, the answer here is no.
Obtaining a sample and making H-NMR measurements is pre-solution activity which is extra-solution activity. It is performed to gather data to then perform the judicial exception. See MPEP 2105.06(g). After the claimed judicial exceptions of “comparing,” and “confirming,” nothing further is done, so there is no particular practical application.
Step 2B: Does the claim recite any elements which are significantly more than the natural correlation or abstract idea?
Again for Claim 1 the answer is no.
Obtaining a sample and making H-NMR measurements on said samples (even for lysine) is well understood, routine and conventional (WURC) in the art. Aside from this, nothing other than the judicial exception steps of (diagnosis, prognosis, comparing, or confirming) are claimed.
Things that are WURC do not make the claims significantly more. See MPEP 2106.05(d)II. No specific measuring or transformation or non-routine analysis is claimed. This is especially the case at the level of generality claimed.
claimed which makes the claims significantly more than the judicial exceptions.
For the dependent claims we would look to see if they add limitations that change the above analysis (e.g. does the new limitation integrate into a practical application or amount to significantly more?). Here, none of the dependent claims 52-70 integrate the abstract idea into a practical application at Step 2A, 2, nor do they amount to significantly more at Step 2B.
Claims 2 specifies that the method is for confirming relapse if values after found above or below reference or standards. This is still general comparison and a natural correlation so this does not change matters with respect to the 101 rejection.
Claims 3 specifies that the method is for determining relapse or prognosis if values after found above or below reference or standards. This is still general comparison and a natural correlation so this does not change matters with respect to the 101 rejection.
Claims 4 specifies that the method is for determining relapse or prognosis if values after found above or below reference or standards. This is still general comparison and a natural correlation so this does not change matters with respect to the 101 rejection.
Claims 5 specifies that the method is for monitoring multiple sclerosis or response to therapy, if values after found above or below reference or standards, however doesn’t require any particular and specific treatment in the claims. This is still general comparison and a natural correlation so this does not change matters with respect to the 101 rejection.
Claims 6 specifies that the method is for monitoring multiple sclerosis or response to therapy, if values after found above or below reference or standards, however doesn’t require any particular and specific treatment in the claims. This is still general comparison and a natural correlation so this does not change matters with respect to the 101 rejection.
Claims 14, specifies that the sample is blood. Taking blood samples are WURC, so does not add anything significantly more to the claims. This also is not a practical application as the samples are only used to gather data to perform the judicial exception.
Claim 16 specifies that the metabolites are determined using H-NMR, or has been determined using this method. Not only does this leave the claim open to no actual measurement occurring within the boundaries or the claim and only mental process happening, but even if H-NMR is used, it is considered to be used for data gathering so does not practically apply and is also WURC, so does not add significantly more.
Claims 19-20 specify that more metabolites are detected or measured. As claimed these are still done as data gathering and are part of the natural correlation, so this does nothing to practically apply nor to add significantly more to the judicial exceptions.
Claim 21 specifies what the disease which is diagnosed could be. Again—the disease is part of the claimed judicial exception/ natural correlation itself. Therefore, does not practically apply nor add significantly more.
Claim 22, specifies that an output is recorded on a data-storage medium. As claimed, this storage medium is a general-purpose computer as does not do anything which practically applies nor which adds significantly more. Even moreso, it does not seem to offer any improvement in the functioning of the computer nor in the art.
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 1-6, 14, 16 & 19-22 are rejected under U.S.C. 103 as being obvious by LOREFICE in Assessing the Metabolomic Profile of Multiple Sclerosis Patients Treated with Interferon Beta 1a by H-NMR Spectroscopy in view of MOUSSALLIEH in Serum analysis by H Nuclear Magnetic Resonance in view of PODLECKA in Altered Cerebrospinal Fluid Concentrations of Hydrophobic and Hydrophilic Compounds in Early Stages of Multiple Sclerosis-Metabolic Profile Analyses (as cited on IDS dated 02/27/2023) and further in view of RUS in US 20160194714.
With respect to Claim 1, LOREFICE teaches of a method for detecting/diagnosing multiple sclerosis in a patient and also of identifying if a treatment is working (a patient’s response to therapy) (abstract).
LOREFICE further teaches analyzing the changes in metabolites by high-resolution nuclear magnetic resonance spectroscopy (H-NMR) (abstract), which includes detection of lysine (abstract, Page 801, column 2, Table 4).
Even more specifically, LOREFICE teaches of that when determining response to therapy, the patients are classified into non-responders (NR) to the therapy and also responders (R) to the therapy (Page 799, Table 3).
LOREFICE teaches that biomarkers such as lysine in the sample from the patients are compared to healthy control samples/reference samples (Page 798, Table 1 and Table 2 & Page 798, column 1, last paragraph and column 2, last paragraph). LOREFICE teaches of determining that the patients are responsive or not responsive to the therapy based on the comparison (abstract).
LOREFICE teaches that lysine is measured as higher in responder patients versus the non-responder patients (Page 802, column 1, paragraph 1).
The biomarker amounts including lysine, is determined by way of detecting chemical shifts in the H-NMR (Page 799, column 1, paragraph 2 and column 2, paragraph 1), and further teach of analyzing the chemical shifts between 0.6 ppm and 9ppm, excluding the regions between 4.68 and 5.2 ppm and between 5.32 and 5.96 ppm and then normalizing the data through statistical methods (Page 799, column 2, paragraphs 2-end of column).
LOREFICE does not call out specifically the claimed chemical shift applicant attributes to lysine at 1.37-1.55 ppm, 1.65-1.75 ppm, 1.83-1.94 ppm, or 3.00-3.05ppm, however this is included in the range in which LOREFICE detects of 0.6 ppm and 9ppm, and does not include the regions LOREFICE excludes 4.68 and 5.2 ppm and between 5.32 and 5.96. Since the exact same method claimed, H-NMR , is used and the exact same compound is detected, lysine, and LOREFICE specifically teaches lysine and detection range that includes the claimed ranges for lysine, LOREFICE inherently teaches these chemical shift detections as they are a material property of the claimed compound, lysine.
Since LOREFICE does not particularly call out the chemical shift associated with Lysine, as claimed, PODLECKA is used to remedy this.
PODLECKA teaches of a method for analysis and diagnosis of Alzheimer’s disease(abstract), using detection by H-NMR and further teaches of identifying Lysine (Lys) at a chemical shift of 1.72 (Table 2, 7 lines from bottom), which falls into the claimed range of 1.65-1.75.
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 lysine as is done in PODLECKA in the method of LOREFICE, since it is shown to have statistical significance (Table 2 description). Further, PODLECKA teaches that the chemical shift regions that are already taught in LOREFICE, could necessarily include detection of lysine if present at chemical shift of 1.72 ppm.
LOREFICE and PODLECKA do not teach of lysine association with multiple sclerosis relapse or poor prognosis.
RUS is used to remedy this and teaches of methods of determining multiple sclerosis relapse in patients (abstract). RUS further teaches of detecting lysine (paragraph 0035, 0106).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect multiple sclerosis relapse as is done in RUS in the methods of LOREFICE and PODLECKA due to the need in the art and potential advantage of identifying if a patient already diagnosed with multiple sclerosis will experience a relapse in order to aid clinicians in prescribing treatment (RUS, paragraph 0006).
With respect to Claim 2, see claim 1 rejection. Further, LOREFICE teaches of the invention as shown above, and further teaches of detection of the biomarkers above the level of a references or control (Page 801, column 1, last paragraph) but does not teach of detection of a relapse. PODLECKA also teaches of the inventions as shown above, but LORIFICE and PODLECKA do not teach of lysine association with multiple sclerosis relapse or poor prognosis.
RUS is used to remedy this and teaches of methods of determining multiple sclerosis relapse in patients (abstract). RUS further teaches of detecting lysine (paragraph 0035, 0106).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect multiple sclerosis relapse as is done in RUS in the methods of LOREFICE and PODLECKA due to the need in the art and potential advantage of identifying if a patient already diagnosed with multiple sclerosis will experience a relapse in order to aid clinicians in prescribing treatment (RUS, paragraph 0006).
With respect to Claim 3, see claim 1 rejection. Further, LOREFICE teaches of the invention as shown above, and further teaches of detection of the biomarkers above the level of a references or control (Page 801, column 1, last paragraph) but does not teach of detection of a relapse. PODLECKA also teaches of the inventions as shown above, but LORIFICE and PODLECKA do not teach of lysine association with multiple sclerosis relapse, which can be considered poor prognosis through broadest reasonable interpretation (BRI).
RUS is used to remedy this and teaches of methods of determining multiple sclerosis relapse in patients (abstract). RUS further teaches of detecting lysine (paragraph 0035, 0106).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect multiple sclerosis relapse as is done in RUS in the methods of LOREFICE and PODLECKA due to the need in the art and potential advantage of identifying if a patient already diagnosed with multiple sclerosis will experience a relapse in order to aid clinicians in prescribing treatment (RUS, paragraph 0006).
With respect to Claim 4, see claim 1 rejection. Further, LOREFICE teaches of the invention as shown above, and further teaches of detection of the biomarkers above the level of a references or control (Page 801, column 1, last paragraph) but does not teach of detection of a relapse. PODLECKA also teaches of the inventions as shown above, but LORIFICE and PODLECKA do not teach of lysine association with multiple sclerosis relapse, which can be considered poor prognosis through broadest reasonable interpretation (BRI).
RUS is used to remedy this and teaches of methods of determining multiple sclerosis relapse in patients (abstract). RUS further teaches of detecting lysine (paragraph 0035, 0106).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect multiple sclerosis relapse as is done in RUS in the methods of LOREFICE and PODLECKA due to the need in the art and potential advantage of identifying if a patient already diagnosed with multiple sclerosis will experience a relapse in order to aid clinicians in prescribing treatment (RUS, paragraph 0006).
With respect to Claim 5, see claim 1 rejection. Further, LOREFICE teaches of the invention as shown above, and further teaches of detection of the biomarkers above the level of a references or control (Page 801, column 1, last paragraph) but does not teach of detection of a relapse. PODLECKA also teaches of the inventions as shown above, but LORIFICE and PODLECKA do not teach of lysine association with multiple sclerosis relapse, which can be considered poor prognosis through broadest reasonable interpretation (BRI).
RUS is used to remedy this and teaches of methods of determining multiple sclerosis relapse in patients (abstract). RUS further teaches of detecting lysine (paragraph 0035, 0106).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect multiple sclerosis relapse as is done in RUS in the methods of LOREFICE and PODLECKA due to the need in the art and potential advantage of identifying if a patient already diagnosed with multiple sclerosis will experience a relapse in order to aid clinicians in prescribing treatment (RUS, paragraph 0006).
With respect to Claim 6, see claim 1 rejection. Further, LOREFICE teaches of the invention as shown above, and further teaches of detection of the biomarkers above the level of a references or control (Page 801, column 1, last paragraph) but does not teach of detection of a relapse. PODLECKA also teaches of the inventions as shown above, but LORIFICE and PODLECKA do not teach of lysine association with multiple sclerosis relapse or poor prognosis.
RUS is used to remedy this and teaches of methods of determining multiple sclerosis relapse in patients (abstract). RUS further teaches of detecting lysine (paragraph 0035, 0106).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect multiple sclerosis relapse as is done in RUS in the methods of LOREFICE and PODLECKA due to the need in the art and potential advantage of identifying if a patient already diagnosed with multiple sclerosis will experience a relapse in order to aid clinicians in prescribing treatment (RUS, paragraph 0006).
With respect to Claim 14, LOREFICE teaches of detection in blood samples by H-NMR before and after therapy (Page 798, column 2, paragraph 1).
With respect to Claim 16, LOREFICE teaches of detection in blood samples by H-NMR before and after therapy (Page 798, column 2, paragraph 1).
With respect to Claim 19, LORIFICE teaches of detecting multiple chemical shifts of bins between 4.68 and 5.2 ppm and that the bins are divided every .04 ppm (Page 799, column 2, paragraph 1). LORIFCE also teaches of detecting multiple different biomarkers by this method including lysine (Abstract). Since LOREFICE does not particularly call out the chemical shift associated with Lysine, as claimed, PODLECKA is used to remedy this.
PODLECKA teaches of a method for analysis and diagnosis of Alzheimer’s disease(abstract), using detection by H-NMR and further teaches of identifying Lysine (Lys) at a chemical shift of 1.72 (Table 2, 7 lines from bottom), which falls into the claimed range of 1.65-1.75.
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 lysine as is done in PODLECKA in the method of LOREFICE, since it is shown to have statistical significance (Table 2 description). Further, PODLECKA teaches that the chemical shift regions that are already taught in LOREFICE, could necessarily include detection of lysine if present at chemical shift of 1.72 ppm.
LOREFICE and PODLECKA do not teach of lysine association with multiple sclerosis relapse or poor prognosis.
RUS is used to remedy this and teaches of methods of determining multiple sclerosis relapse in patients (abstract). RUS further teaches of detecting lysine (paragraph 0035, 0106).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect multiple sclerosis relapse as is done in RUS in the methods of LOREFICE and PODLECKA due to the need in the art and potential advantage of identifying if a patient already diagnosed with multiple sclerosis will experience a relapse in order to aid clinicians in prescribing treatment (RUS, paragraph 0006).
With respect to Claim 20, LORIFICE teaches of detecting multiple chemical shifts of bins between 4.68 and 5.2 ppm and that the bins are divided every .04 ppm (Page 799, column 2, paragraph 1). LORIFCE also teaches of detecting multiple different biomarkers by this method including lysine (Abstract).
Since LOREFICE does not particularly call out the chemical shift associated with Lysine, as claimed, PODLECKA is used to remedy this.
PODLECKA teaches of a method for analysis and diagnosis of Alzheimer’s disease(abstract), using detection by H-NMR and further teaches of identifying Lysine (Lys) at a chemical shift of 1.72 (Table 2, 7 lines from bottom), which falls into the claimed range of 1.65-1.75.
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 lysine as is done in PODLECKA in the method of LOREFICE, since it is shown to have statistical significance (Table 2 description). Further, PODLECKA teaches that the chemical shift regions that are already taught in LOREFICE, could necessarily include detection of lysine if present at chemical shift of 1.72 ppm.
LOREFICE and PODLECKA do not teach of lysine association with multiple sclerosis relapse or poor prognosis.
RUS is used to remedy this and teaches of methods of determining multiple sclerosis relapse in patients (abstract). RUS further teaches of detecting lysine (paragraph 0035, 0106).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect multiple sclerosis relapse as is done in RUS in the methods of LOREFICE and PODLECKA due to the need in the art and potential advantage of identifying if a patient already diagnosed with multiple sclerosis will experience a relapse in order to aid clinicians in prescribing treatment (RUS, paragraph 0006).
With respect to Claim 21, LOREFICE and PODLECKA teach of the claims as shown above, but do not teach of lysine association with multiple sclerosis relapse or poor prognosis.
RUS is used to remedy this and teaches of methods of determining multiple sclerosis relapse in patients, and specifically of determining relapsing-remitting multiple sclerosis (RRMS) (abstract). RUS further teaches of detecting lysine (paragraph 0035, 0106).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect multiple sclerosis relapse as is done in RUS in the methods of LOREFICE and PODLECKA due to the need in the art and potential advantage of identifying if a patient already diagnosed with multiple sclerosis will experience a relapse in order to aid clinicians in prescribing treatment (RUS, paragraph 0006).
With respect to Claim 22, LOREFICE teaches of storing and performing data maintenance processing on software (Page 799, column 2, paragraphs 2-end of column).
Conclusion
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached on 571-270-7698. The fax phone number for the organization wherehis application or proceeding is assigned is 571-273-8300.
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/REBECCA M FRITCHMAN/ Primary Examiner, Art Unit 1758
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