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 application 18/027609 election response filed 11/24/2025.
Claims 1-4, 10-13, & 56 are pending and have been fully examined.
Election/Restrictions
Applicant's election with traverse of Claims 1-4, 10-13, & 56 in the reply filed on 11/24/2025 is acknowledged. The traversal is on the ground(s) that a preliminary amendment was filed when the application initially entered the national stage. This is not found persuasive because the initial filing in the U.S. did not have these preliminary amendments in them. However--- an amendment was filed in response to the restriction requirement dated 09/23/2025 and this does in fact have only claims 1-4, 10-13, & 56 listed. All of these claims are drawn towards one invention--- the claimed method of treating. Therefore, all pending claims as of the most recent amendment dated 11/24/2025 are drawn towards one invention and therefore they have all been examined.
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 of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
The claimed invention of claims 1-4, 10-13, & 56 are directed to a natural correlation without significantly more.
Through 101, inquiry analysis:
Step 1: Is the claim directed to a statutory category of invention?
Yes, independent Claim 1 and the claims that depend therefrom are drawn towards a statutory category of a method.
Step 2A, Prong One: Identify if there is a law of nature/natural phenomenon/abstract ideas.
For independent Claim 1 and those dependent therefrom, they recite the relationship/natural correlation of the claimed biomarkers (wherein the biomarker is L-malic acid, fumaric acid, and HPHPA) with autism spectrum disorder. This is a natural correlation/law of nature judicial exception (shown in the comparison of biomarkers levels to a control, and identifying the patient is affected/needing treatment based on that).
Claim 1 and those dependent therefrom also contain limitations for “determining,” “risk,” and “comparing,” values to a control and dependent on the comparison the “identifying,” which as claimed is akin to diagnosing happens. These things as claimed are mental processes which are abstract idea judicial exceptions.
Further, Claim 1 recites, “assessing or determining,” and “comparing,” to a control which is an ASD negative individual and “identifying,” which are all mental processes or simple math and therefore abstract idea judicial exceptions.
Step 2A Prong Two: Are the judicial exceptions integrated into practical application?
The judicial exceptions are not integrated into a practical application in independent claim 1.
Claim 1 recites the additional elements including:
“measuring,”
providing a blood, plasma, serum, or urine same; and
“treating the subject in need thereof,” “with an ASD treatment regime.”
The claimed providing of a biological sample does nothing to practically apply the judicial exceptions. It is pulled (and the determining or assessing) happens from there to use the claimed natural correlation judicial exception. Therefore—as claimed it is extra-solution activity.
With respect to the claimed, “measuring,” no actual measuring or detecting takes place and instead the levels of the claimed biomarkers are done through, “determining or assessing,” of what is in a biological sample. Even if general measurement device was claimed, such as GC-MS--- for general measuring and especially when recited at a high level of generality, there is no meaningful limitation, such as a particular machine or a transformation of a particular article. As claimed the measuring is done to gather data to perform the claimed judicial exceptions and there is nothing claimed which distinguishes it from conventional data gathering activity. Data gathering to be used in an abstract idea or with the claimed natural correlation, is insignificant extra-solution activity, and therefore not a particular practical application. See MPEP 2106.05(g).
Further, it is well established that the mere physical or tangible nature of additional elements such as the obtaining and detecting steps does not automatically confer eligibility on a claim directed to an abstract idea (or natural correlation) (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)).
Further—after the biomarker levels are determined (data is gathered) and a judicial exception of “comparing,” and the implicit diagnosis is performed, a general treatment, “treating the subject in need thereof…with an ASD treatment regimen.” However, due to the generality claimed this is not considered particular treatment, so does not practically apply the judicial exceptions. As claimed, the treatment is akin to “administering a suitable treatment,” which has been shown to not be particular treatment. See MPEP 2106.04(d)(2)(a):
“Consider a claim that recites the same abstract idea and “administering a suitable medication to a patient.” This administration step is not particular, and is instead merely instructions to “apply” the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application.”
Step 2B: Do the claims recite any elements which are significantly more than the judicial exceptions?
Independent Claim 1 does not include additional elements that are sufficient to amount to significantly more than the judicial exception because there is no particularity or specificity of measurement, detection, treatment, or other limitations that makes the claims significantly more than the claimed judicial exceptions.
Claim 1 recites the additional elements including:
providing a blood, plasma, serum, or urine same;
“measuring,” and
“treating the subject in need thereof,” “with an ASD treatment regime.”
Both the claimed providing of a biological sample, the claimed general “measuring,” and the claimed generalized treatment for autism do nothing to add significantly more to the judicial exceptions.
Taking of a blood sample or other biological sample from a patient, “measuring,” and treatment for the disease that that is diagnosed (autism) are things that are well-understood, routine and conventional activity (WURC) for those in the field of diagnostics. This is evidenced by the fact that prior art teaches of them, and is especially true at the level of generality claimed.
Further MPEP 2106.05 (d) II for examples of laboratory techniques that have been shown to be routine and conventional. “The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity…”
The dependent claims undergo a similar analysis.
Claim 2 does not change the matters above. It adds that a spectroscopy technique is used. This remains a mechanism to perform a data pull to accomplish the judicial exceptions, so does not practically apply. Spectroscopy is also WURC in the art so does not add significantly more.
Claim 3 does not change the matters above. This is especially true at the level of generality claimed for the claimed treatments. Possible treatments a-c read as making some kind of dietary or nutritional adjustment, but does say more exactly how they are adjusted. People adjust their diet, gut microbiota, and nutritional supplements on a daily basis. Step d), “behavior training,” also reads so broadly that it is not considered a treatment which practically applies at the level of generality claimed. For e), “adjusting,” the “levels,” of the biomarkers which are detected, is also not specific and particular treatment at the level of generality claimed as it is not said how they are adjusted and if so using what kind of treatment to adjust them. Therefore, none of these things practically apply the judicial exceptions. Also, at the level of generality claimed they are all WURC in the art and therefore do not add significantly more.
Claim 4 does not change the matters above. It claims that the “adjustment,” “continues until an improvement in the behavioral performance in the subject is observed.” However, again--- it is not said how or with what the claimed “adjustment,” happens. Therefore this is not specific and particular treatment at the level of generality claimed as it is not said how they are adjusted and if so using what kind of treatment to adjust them. Therefore, none of these things practically apply the judicial exceptions. Also, at the level of generality claimed they are all WURC in the art and therefore do not add significantly more.
Claim 10 does not change the matters above. It adds that a spectroscopy technique which could be something like GC-MS is used. This remains a mechanism to perform a data pull to accomplish the judicial exceptions, so does not practically apply. GC-MS and the other claimed detection techniques are also WURC in the art so does not add significantly more.
Claim 11 does not change the matters above. It claims that the claimed comparing/comparison is done using a multivariate statistical analysis. However, at the level of generality claimed comparing using multivariate statistical analysis, still reads as performing general math by the human mind. Therefore, this is an abstract idea and does nothing to practically apply, nor does it add significantly more.
Claim 12, does not change the matters above. It claims that the claimed comparing/comparison is done using a multivariate statistical analysis which is either principal component analysis or partial least squares projects to latent structures. However, at the level of generality claimed comparing using the claimed multivariate statistical analysis, still reads as performing general math by the human mind. Therefore, this is an abstract idea and does nothing to practically apply, nor does it add significantly more.
Claim 13 does not change the matters above. It specifies where/who the sample is taken from. However a biological sample is still a biological sample. Taking the sample is used for data pull to perform the judicial exceptions so does not practically apply. It is also WURC so does not add significantly more.
Claim 56 does not change the matters above. Claim 56 adds that the spectroscopy unit is linked to a communication technology or processing device, directly or wirelessly and that the processing device has a memory which can store measurement data. However, again, at the level of generality claimed, this does not to practically apply the judicial exceptions. Also linking spectroscopy units to communication technology or processing device, directly or wirelessly and processing devices with memory which can store measurement data are WURC in the art so does not add significantly more.
Claim Objections
Claim 1 is objected to because of the following informalities:
In Claim 1, d), steps i-iii, “are,” is used to describe singular compounds. These steps should instead say, “fumaric acid is…” “L-malic acid is,” and “”HPHPA is….”
Appropriate correction is required.
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 1-4, 10-13, & 56 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 1, the phrase, “in need thereof” in claim preamble and claim body is a relative term which renders the claim indefinite. The term “in need thereof,” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The phrase, “in need thereof,” can mean different things to different people so is unclear in the claim. One person might think a person with autism spectrum disorder having the same symptoms might need treatment, while another person might not think the same person needs treatment. Therefore, this is a relative term and requires correction.
Further with respect to Claim 1, in step d), i) & ii)--- “at least about 2 times or less,” is confusing/unclear since the phrase requires “ at least,” “about 2 times,” but can also be “or less,” meaning that the levels do not need to be “at least about 2 times.” What the required level is, is unclear in the claims and requires correction.
Further with respect to Claim 1, step d), “so identified in step (d),” it is unclear if applicant means that the patient who is treatment has been identified as having ASD or not,” “so identified in step (d),” could mean other things. Applicant should clear this up to prevent confusion.
With respect to Claim 3, in steps a-e, “the subject diagnosed,” fails to have proper antecedent basis,” as “subject diagnosed,” was not claimed prior to this in either Claim 3 or Claim 1 from which Claim 3 depends.
With respect to Claim 4, “the behavioral performance,” fails to have proper antecedent basis as “behavioral performance,” was not mentioned priorly to this in the claims.
With respect to Claim 11, it depends on Claim 1, however, “4-hydroxymandelic acid,” is not required in Claim 1 and instead fumaric acid is claimed in addition to the other two biomarkers of L-malic acid and HPHPA. Therefore, it is unclear if applicant is no longer using fumaric acid in Claim 11, or if the inclusion of 4-hydroxymandelic acid is being further added, or if instead it is a typo. Applicant should clear this up in the claims. (4 hydroxymandelic acid is also in Claims 3-4, but is claimed as sort of a potential treatment wherein the level of it can be adjusted).
With respect to Claim 13, the claimed ranges are confusing/unclear as 3 years or less,” the “or less,” is not included in the same range really as “between 3 and 10 years.” It seems what is claimed for option a) in Claim 13 “10 years or less,” includes all of options a-d). Therefore, as claimed it seems applicant is claiming a broad limitation, “10 years or less,” and then trying to narrow it down in the same claim with other ranges. Therefore, the range required is unclear.
Claims 2-4, 10-13, & 56 are also rejected due to their dependency on Claim 1.
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, 10-13, & 56 are rejected under 35 U.S.C. 103 as being obvious over YOU in US 20220373563 in view of XIONG in Urinary3-(3-Hydroxyphenyl)-3-hydroxypropionid Acid, 3-Hydroxyphenylacetic Acid, and 3-Hydroxyhippuric Acid Are Elevated in Children with Autism Spectrum Disorders
(as cited on IDS dated 06/14/2023).
With respect to Claim 1, YOU teaches of a method of diagnosis and of a device using a metabolite as a marker. The method comprises: measuring the content of at least one marker in a sample of a subject and comparing same with the content of the corresponding marker in a healthy control, and of using an algorithm constructed by machine learning to process the content of the marker. Particularly, the marker is a metabolite in human urine or blood. The change pattern of a metabolite in urine is mined by means of a machine learning algorithm to provide diagnoses for children suffering from ASD. The device based on a predetermined algorithm provided by the present application can provide a new strategy for diagnosis of ASD (abstract, paragraph 0013).
YOU more specifically teaches of assessing for the presence of metabolites/ a metabolite profile including fumaric acid, and malic acid (paragraphs 0016-0017). (L-malic acid as claimed, is the naturally occurring, biologically active form of malic acid and is the form of malic acid that is metabolized for energy in the human body. DL malic acid is synthetic and not naturally found in living systems, but DL-malic acid is commonly used in supplements and drinks.) YOU even further teaches of assessing for HPHPA (Table I).
YOU even further teaches of using the method for early treatment of autism spectrum disorder--- which reads on the broadly claimed “treating the subject in need thereof with an ASD treatment regimen,” since any treatment for ASD can be considered an ASD treatment regimen (paragraph 0003).
More specifically to the claims, YOU teaches of providing the sample (paragraph 0005),
Detecting/measuring the content of the biomarkers (paragraph 0006, 0050-0051),
Using machine learning algorithm to process/ “assessing,” data as claimed to obtain a mathematical model for diagnosing autism spectrum (paragraph 0007), and
Comparing the concentration levels of the measured biomarkers to a control sample taken from an ASD-negative individual (YOU teaches the control group being a healthy group, which in this context means autism negative (abstract, paragraph 0091), through broadest reasonable interpretation (BRI)),
Identifying a subject in need to treatment if the measured concentration of fumaric and malic acid are less than the control sample (Table 3). This less than reads on the claimed ranged of identifying, the levels of fumaric acid and malic acid being “at least about 2 times or less than the levels,” since the levels can just be “less than,” “the at least about 2 times,” in comparison to control through broadest reasonable interpretation as this limitation is unclear as shown in the 112 rejection.
YOU does not teach specifically of HPHPA being at least 10 times greater than found in the control, or of fumaric and malic acid being specifically two times less than the control. Further, though YOU teaches of using the method to identify early treatment, YOU does not teach of a positive treatment step.
XIONG is used to remedy this and more specifically teaches of a GC- MS method to detect biomarkers of autism where HPHPA is measured as a biomarker (abstract). Further, XIONG teaches that the measured levels in autism patients of HPHPA are over 10 times greater than those in the control patients (looking at the mean levels on Table 1).
Even further, XIONG teaches of administering oral vancomycin treatment to the patient with autism who has high levels of HPHPA (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of measuring HPHPA levels 10 times or more higher than control and then treating the patient as is done in XIONG in the method of YOU due to the advantages such treatment with vancomycin has shown for treatment as patients have shown improved eye contact and communication and also with respect to intestinal symptoms in children with autism (Page 4, column 1 & column 2, first paragraph).
With respect to Claim 2, YOU teaches of measuring a urine or blood sample (paragraph 0013), using gas chromatography and mass spectrometry (paragraphs 0050-0051). As shown by the instant application (see instant application, Claim 10—applicant considers gas chromatography and gas chromatography mass spectrometry a spectroscopic technique).
With respect to Claim 3, YOU teaches of the invention as shown above, but does not teach of a positive treatment step.
XIONG is used to remedy this and more specifically teaches of a GC- MS method to detect biomarkers of autism where HPHPA is measured as a biomarker (abstract). Further, XIONG teaches that the measured levels in autism patients of HPHPA are over 10 times greater than those in the control patients (looking at the mean levels on Table 1).
Even further, XIONG teaches of administering oral vancomycin treatment to the patient with autism who has high levels of HPHPA (abstract). Vancomycin is a treatment which adjusts the composition of gut microbiota. See reason for combination for Claim 1.
With respect to Claim 4, YOU teaches of the invention as shown above, but does not teach of a positive treatment step.
XIONG is used to remedy this and more specifically teaches of a GC- MS method to detect biomarkers of autism where HPHPA is measured as a biomarker (abstract). Further, XIONG teaches that the measured levels in autism patients of HPHPA are over 10 times greater than those in the control patients (looking at the mean levels on Table 1).
Even further, XIONG teaches of administering oral vancomycin treatment to the patient with autism who has high levels of HPHPA (abstract) and that this changes/adjusts the level of HPHPA so that it significantly decreases(abstract). Vancomycin is a treatment which adjusts the composition of gut microbiota. See reason for combination for Claim 1. XIONG teaches that this treatment has shown some affect on improved eye contact and communication in patients with autism (Page 4, column 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of treating the patient as is done in XIONG in the method of YOU due to the advantages such treatment with vancomycin has shown for treatment as patients have shown improved eye contact and communication and also with respect to intestinal symptoms in children with autism (Page 4, column 1 & column 2, first paragraph).
With respect to Claim 10, YOU teaches of measuring a urine or blood sample (paragraph 0013), using gas chromatography and mass spectrometry (paragraphs 0050-0051).
With respect to Claim 11, YOU teaches of using a multivariate statistical analysis which is partial least squares (paragraph 0011, 0057, 0097, 0014-0015).
With respect to Claim 12, YOU teaches of using a multivariate statistical analysis which is partial least squares (paragraph 0011, 0057, 0097, 0014-0015).
YOU does not teach of using principal component analysis.
XIONG teaches of analysis of the data by principal component analysis/PCA (Page 2, column 2, paragraph 2, last 2 lines).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success due to the advantage PCA has for differentiating samples (Page 2, column 2, last paragraph, lines 1-3).
With respect to Claim 13, YOU teaches of the subject being a child who is 3 years or younger (paragraph 0032, 0069). YOU also teaches of using an autism group and a control group (paragraph 0098). Also- YOU teaches of the control group being a healthy group, which in this context means autism negative (abstract, paragraph 0091). The healthy groups read on the ASD- negative sample groups.
With respect to Claim 56, YOU teaches of measuring a urine or blood sample (paragraph 0013), using gas chromatography and mass spectrometry (paragraphs 0050-0051). As shown by the instant application (see instant application, Claim 10—applicant considers gas chromatography and gas chromatography mass spectrometry a spectroscopic technique). YOU further teaches of using a machine learning algorithm, which is an algorithm used by a computer (which has a processor/processing device and memory) to simulate or implement human learning behaviors (paragraph 0074, 0075). The machine learning algorithm processes the data to obtain a diagnostic algorithm for autism (paragraph 0007, 0009, 0028-0029, 0095-0096, Table IV). Since the data from the gas chromatography mass spectrometry is used by the machine learning algorithm, that means it is “directly or wirelessly linked,” to a processing device through broadest reasonable interpretation (BRI)).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
WEST in WO 2015006160 (as cited on IDS dated 06/14/2023) teaches a method identifying biomarkers for autism (Page 17, 1st paragraph), in biofluids (Page 19, 1.24), analysis of biomarkers by mass spectrometry and comparison to a control (Page 17, 1st paragraph), and further teaches of many of the disclosed, non-claimed metabolites (Table 9, and Page 27, last paragraph). WEST also teaches of determining statistical significance (Page 21, 3rd paragraph).
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