DETAILED ACTION
Notice of AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Withdrawal Objections and Rejections
Applicant's response, filed 11/25/2025, has been fully considered.
In view of the amendment and remarks from 11/25/2025, the objection to the drawings, the objection to the specification and the following claim rejections are withdrawn:
101 rejections of claims 27-29 and 33-37 and
103 rejections of claims 26-37.
The following rejections and/or objections are either maintained or newly applied for claims 26 and 30-32. They constitute the complete set applied to the instant application. Herein, "the previous Office action" refers to the Non-Final Rejection of 08/06/2025.
Status of the Claims
Claims 26 and 30-32 are pending.
Claims 1-25, 27-29 and 33-37 are canceled.
Claim 26 is independent.
Claim 26 is objected to.
Claims 26 and 30-32 are rejected.
Priority
This US Application 17/619,327 (12/15/2021) is a 371 of PCT/CN2019/083944 (04/23/2019) claims no further priority herein as reflected in the filing receipt mailed on Aug. 09, 2022. The claims to the benefit of priority are acknowledged and the effective filing date of claims 26 and 30-32 is 04/23/2019.
Claim objections
Claim 26 is objected to because of the following informality: colons should begin lists in which list elements are separated by new lines, "essentially of" should be followed by a colon with the following list begging with "Phenyllactic acid … " located in a new and indented line. As set forth in 37 CPR 1.75, where a claim sets forth a plurality of steps, each step of the claim should be separated by a line indentation (see MPEP 608.0l(i)). Appropriate correction is required.
Claim Interpretation
The following claim interpretations apply to all instances of the following terms throughout all claims:
112(f) interpretation of particular recitations
Recited "detection device" (claim 26)
The above recitations include means (or an equivalent, nonce term, here "device") and function and/or result (here "detection").
The above recitations are not sufficiently well-known and not accompanied by sufficient structure in the claims to prevent invoking. Therefore, each is interpreted as invoking.
Having invoked, each above recitation has been analyzed as clearly linking to sufficient structure in the specification, as supported at (pg. 6 lines 24-25). Thus, the above recitations have been interpreted as properly invoking 112(f).
Recited "calculation and determination unit" (claim 26)
The above recitations include means (or an equivalent, nonce term, here "unit") and function and/or result (here "calculation and determination").
The above recitations are not sufficiently well-known and not accompanied by sufficient structure in the claims to prevent invoking. Therefore, each is interpreted as invoking.
Having invoked, each above recitation has been analyzed as clearly linking to sufficient structure in the specification, as supported at (pg. 25 lines 6-10). Thus, the above recitations have been interpreted as properly invoking 112(f).
Regarding recitations above interpreted as invoking 112(f)
If applicant does not intend to have interpreted under 112(f), applicant may: (1) amend to avoid them being interpreted under 112(f) (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitations recite sufficient structure to perform the claimed function so as to avoid them being interpreted under 112(f).
Claim Rejections - 35 USC § 112(b)
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 26 and 30-32 are rejected under 35 U.S.C. 112(b)as being indefinite for failing to particularly point out and distinctly claim the subject matter the invention. Dependent claims are rejected similarly, unless otherwise noted below. The following issues cause the respective claims to be rejected under 112(b) as indefinite:
Claim 26 recites "the XGBoost … computer algorithm" which requires but lacks antecedent basis. There is no previous recitation of any computer algorithm in the claims. This rejection may be overcome by amending the claim to read "a XGBoost … computer algorithm"."
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.
Claims 26 and 30-32 are rejected under 35 USC § 101 because the claimed inventions are directed to one or more Judicial Exceptions (JEs) without significantly more. Regarding JEs, "Claims directed to nothing more than abstract ideas..., natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 §I). Abstract ideas include mathematical concepts and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)).
101 background
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Analysis of instant claims
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Claims 26 and 30-32 are directed to a 101 machine or manufacture, here a "system," comprising at least one non-transitory element such as "a fluid chromatography detection device..." [Step 1: claims 26 and 30-32 - Yes].
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Background
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in instant claim 26, include the terms:
• "calculation";
• "XGBoost eXtreme Gradient Boosting computer algorithm"; and
• "higher weights assigned".
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one having ordinary skill in the art. Thus, the recited terms correspond to verbal equivalents of mathematical concepts (MPEP 2106.04(a)(2)). A mathematical concept need not be expressed in mathematical symbols, because "words used in a claim operating on data to solve a problem can serve the same purpose as a formula." In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). In this instant disclosure, (pg. 11 lines 17-24) describes the claimed "computer algorithm" using actions executed by a group of mathematical steps (i.e. assigning weights) in a form of a mathematical algorithm; thus mathematical concepts.
Mental processes, defined as concepts or steps practically performed in the human mind such as steps of observations, evaluations, judgments, analysis, opinions or organizing information include “obtain an indication of whether the subject suffers from autism spectrum disorder” (claim 26). Under the BRI, the recited limitations are mental processes because a human mind is sufficiently capable of identify a diagnosis.
Dependent claim 30 recites further details about the autism spectrum disorder. Hence, the claims explicitly recite numerous elements that, individually and in combination, constitute abstract ideas. The instant claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A Prong One: claims 26 and 30-32 - Yes].
Step 2A, 1st prong, 1st Mayo/Alice question: natural product -- MPEP 2106.I and 2106.04
Preliminarily, at this 1st step of the analysis, elements of independent claim 26 (and its dependent claims) are directed to natural products: the presence of markers present in a sample correlated with a condition, i.e. autism. (see MPEP 2106.04(b).I). [Step 2A, 1st prong, law of nature: claims 26 and 30-32 - Yes].
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Background
MPEP 2106.04(d).I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application:
An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
Analysis of instant claims
Instant claim 26 recites additional elements that are not abstract ideas: “calculation and determination unit”. The use of a computer is broadly interpreted and not actually described in the claims. Under BRI, the computer description in this instant specification (pg. 11 line 11) amounts to applying computer methods.
Further steps directed to additional non-abstract elements of a computing device/computer do not describe any specific computational steps by which the "computer parts" perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions.
The recited “accommodating space” and "fluid chromatography detection device" in claim 26 reads on data gathering activity, being a regular physical component to perform testing/assay and insignificant extra-solution activity since this limitation merely serve to gather data that is utilized as input for the judicial exception. See MPEP 2106.05(g) and MPEP 2106.04(d). This limitation is merely an intended use of the claimed invention or a field of use limitation, which cannot integrate a judicial exception as mere data gathering activity, and merely define the type of cancer being detected rather than limiting the physical assay step itself. See MPEP 2106.05(g).
Dependent claims 31-32 recite further details about the sample being tested.
Hence, these are mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)). None of the dependent claims recite any additional non-abstract elements; they are all directed to further aspects of the information being analyzed, the manner in which that analysis is performed, or the mathematical operations performed on the information.
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
In this Step 2A, Prong Two immediately above claim steps and/or elements were identified as part of one or more additional elements. Additional elements are further discussed in Step 2B below.
Here in Step 2A, Prong Two, no additional step or element clearly demonstrates integration of the JE(s) into a practical application.
At this point in examination it is not yet the case that any of the Step 2A, Prong Two considerations enumerated above clearly demonstrates integration of the identified JE(s) into a practical application. Referring to the considerations above, none of 1. an improvement, 2. treatment, 3. a particular machine or 4. a transformation is clear in the record.
For example, regarding the first consideration at MPEP 2106.04(d)(1), the record, including for example the specification, does not yet clearly disclose an explanation of improvement over the previous state of the technology field. The claims do not yet clearly result in such an improvement (pg. 26 lines 15-18) [Step 2A Prong Two: claims 26 and 30-32 - No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during examination that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
Claims directed to “obtain an indication” read on electronically outputting data on a computer which is a conventional computer function (Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 225, 110 USPQ2d 1984 (2014) MPEP 2106.05(d)). As discussed above, limitations regarding providing an indication of a disorder cannot integrate a judicial exception.
It is known in the art that the use of analytical methos gas chromatography and mass spectrometry to investigate the metabolomics of autism spectrum disorders is well-understood, routine and conventional (Mussap et. al. “Metabolomics of autism spectrum disorders: early insights regarding mammalian-microbial cometabolites” Expert Review of Molecular Diagnostics 16(8):869-881 (2016) – pg. 877 col. 1 para. 2).
When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h). [Step 2B: claims 26 and 30-32 - No]
Conclusion: Instant claims are directed to non-statutory subject matter
For these reasons, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not constitute significantly more than the abstract idea, so instant claims 26 and 30-32 are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 101
The Remarks of 11/25/2025 have been fully considered but are not yet persuasive because the Applicant remarks summarizes the amendments made in the claims and do not provide arguments related to the 101 Claim Rejection.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 26 and 30-32 are rejected under 35 U.S.C. 103(a) as being unpatentable over Kałuzna-Czaplinska14 (“Identification of organic acids as potential biomarkers in the urine of autistic children using gas chromatography/mass spectrometry” Journal of Chromatography B. 966:70–76 (2014)) in view of Mussap (“Metabolomics of autism spectrum disorders: early insights regarding mammalian-microbial cometabolites” Expert Review of Molecular Diagnostics 16(8):869-881 (2016)) as evidenced by West (“Metabolomics as a Tool for Discovery of Biomarkers of Autism Spectrum Disorder in the Blood Plasma of Children” PLOS ONE 9(11):e112445 (2014)) in view of Gondalia (“Gastrointestinal microbiology in autistic spectrum disorder: a review” Reviews in Medical Microbiology 21:44–50 (2010)) in view of Pavone et. al. (“A clinical review on megalencephaly: a large brain as a possible sign of cerebral impairment” Medicine 96:26 (2017)) in view of Mello (“Increased oxidative stress in patients with 3-hydroxy-3-methylglutaric aciduria” Mol. Cell. Biochem. 402:149–155 (2015)) in view of Kałuzna-Czaplinska11 (“Noninvasive urinary organic acids test to assess biochemical and nutritional individuality in autistic children” Clinical Biochemistry 44:686–691 (2011)) in view of Bhatti (“Systematic Review of Human and animal Studies examining the efficacy and Safety of N-acetylcysteine (Nac) and N-acetylcysteine amide (Naca) in traumatic Brain injury: impact on Neurofunctional Outcome and Biomarkers of Oxidative Stress and inflammation” Frontiers in Neurology 8(744):1-14 (2018)) in view of West in view of Blazenovick (“Software Tools and Approaches for Compound Identification of LC-MS/MS Data in Metabolomics” Metabolites 8:31 (2018)), as cited on the 8/06/2025 Form PTO-892.
Kałuzna-Czaplinska14 discloses the identification of biomarkers in the urine of autistic children using gas chromatography/mass spectrometry (pg. 70 para. 1). Bullet points indicate the teachings of the instant features over the prior art. Instantly claimed elements which are considered to be equivalent to the prior art teachings are described in bold for all claims.
Claim 26 recites:
an accommodating space to receive a urine sample of a subject; a fluid chromatography detection device detect a plurality of markers of the urine sample to obtain the respective content values of the plurality of markers in the urine sample
Kałuzna-Czaplinska14 teaches the analysis of 1µL of derivatized urine sample injected into an Agi-lent 6890N Network GC system (i.e. a fluid chromatography detection device inherently comprising a space to accommodate the sample) (pg. 71 col. 2 para. 4) to distinguish between autistic and non-autistic children using the metabolomic profiles (pg. 72 col. 2 para. 5) by identifying biological markers can help define autism subtypes (pg. 70 para. 1).
wherein the plurality of markers consists essentially of Phenyllactic acid, 3-Hydroxy-3-Methylglutaric acid, Phosphoric acid, Fumaric acid, 3-Oxoglutaric acid, Aconitic acid, N-Acetylcysteine, Malonic acid, Tricarboxylic acid, Glycolic acid, Creatinine, Malic acid, Oxalic acid, Tartaric acid, Pyruvic acid, 4- Cresol, Carboxycitric acid, 3-Hydroxyglutaric acid, 2-Hydroxybutyric acid, and 2- Oxoglutaric acid
Kałuzna-Czaplinska14 does not teach the list of markers above.
Mussap teaches the metabolomics of autism spectrum disorders and advances in implementing knowledge on the aetiology and early diagnosis of the disease after birth (pg. 869 para. 1); wherein the main results include biomarkers identified as the metabolic fingerprint of autism (pg. 872 col. 2 para. 1) such as 4-hydroxyphenyllactic acid (i.e. classified as a phenyllactic acid - as evidenced by West in pg. 10 Table 4), tartaric acid, phosphoric acid, oxalic acid, glycolic acid, α-hydroxybutyric acid (i.e. 2-hydroxybutyric acid), creatinine (pg. 873 Table 2), fumarate (i.e. ionized form of fumaric acid), 2-oxoglutarate (i.e. ionized form of 2-oxoglutaric acid), pyruvate (ionized form of pyruvic acid) (pg. 874 Fig. 1), cis-aconitate (i.e. isomer of ionized form of aconitic acid) (pg. 875 col.1 para. 1), 3- oxoglutaric acid (pg. 872 col. 2 para. 1), citramalic acid (i.e. methylated malic acid) (pg. 872 col. 2 para. 1), p-cresol (i.e. 4-cresol) (pg. 872 col. 2 para. 1) and tricarboxylic acid (pg. 879 col. 1 para. 4)
Gondalia teaches gastrointestinal microbiology in autistic spectrum disorder and possible involvement of bacteria, viruses and fungi, and their products in autism (pg. 44 para. 1) including analogs of Krebs cycle metabolites such as carboxycitric acid (pg. 48 col. 1 para. 1)
Pavone teaches that accumulation of 3-hydroxyglutaric acid interferes in the energetic metabolism and oxidative stress, provoking neuronal impairment with untreated patients presenting dystonic movement disorders in infancy. (pg. 3 col. 1 para. 3).
Mello teaches that 3-hydroxy-3-methylglutaric aciduria leads to high amounts of 3-hydroxy-3-methylglutaric acid (pg. 149 col. 2 para. 2) and also often leads to life-threatening illness in the neonatal period and in childhood, with acute episodes characterized by vomiting, diarrhea, dehydration, hypothermia, apnea, hepatomegalia, and cardiomyopathy, as well as neurological dysfunction manifested by macrocephalia, lethargy, hypotonia, seizures, and developmental delay (pg. 150 col. 1 para. 2)
Kałuzna-Czaplinska11 teaches noninvasive urinary organic acids test to assess biochemical and nutritional individuality in autistic children (pg. 686 Title) wherein malonic acid was analyzed in urine samples (687 col.2 para. 3)
Bhatti teaches that clinical trials have evaluated N-Acetylcysteine targeting neurological diseases including autism (pg. 2 col. 2 para. 1)
calculation and determination unit to process the content values based on the XGBoost eXtreme Gradient Boosting computer algorithm, with higher weights assigned to the content values of the Phenyllactic acid, the Aconitic acid, the Phosphoric acid, the 3-Oxoglutaric acid, and the Carboxycitric acid to obtain an indication of whether the subject suffers from autism spectrum disorder.
West teaches using machine learning to predict ASD from metabolite data (i.e. according to a predetermined algorithm to obtain an indication of whether the subject suffers from autism spectrum disorder) (pg. 2 col.2 para. 2)
Blazenovick teaches in-silico fragmentation algorithms for annotation of small molecules in chromatography and mass spectrometry based metabolomics (pg. 1 para. 1); wherein retention times can be predicted by using chemical descriptors as input parameters using gradient boosting methods - XGBoost - in machine learning models (i.e. computer algorithm XGBoost) (pg. 9 para. 1)
Mussap teaches the metabolomics of autism spectrum disorders and advances in implementing knowledge on the aetiology and early diagnosis of the disease after birth (pg. 869 para. 1); wherein the main results include biomarkers identified as the metabolic fingerprint of autism (pg. 872 col. 2 para. 1) such as 4-hydroxyphenyllactic acid (i.e. classified as a phenyllactic acid) as evidenced by West (pg. 10 Table 4 West), cis-aconitate (i.e. isomer of ionized form of aconitic acid) (pg. 875 col.1 para. 1), phosphoric acid (pg. 873 Table 2) and 3- oxoglutaric acid (pg. 872 col. 2 para. 1)
Gondalia teaches gastrointestinal microbiology in autistic spectrum disorder and possible involvement of bacteria, viruses and fungi, and their products in autism (pg. 44 para. 1) including analogs of Krebs cycle metabolites such as carboxycitric acid (pg. 48 col. 1 para. 1).
Dependent claim 30 recites "wherein the autism spectrum disorder includes Rett syndrome, childhood disintegration, Asperger's syndrome, or unspecified generalized developmental disorder."
Dependent claim 31 recites "wherein the subject is a human."
Dependent claim 32 recites "wherein the subject is a child."
Kałuzna-Czaplinska14 teaches the identification of biomarkers in the urine of autistic children using gas chromatography/mass spectrometry (pg. 70 Title); wherein autism spectrum disorders are characterized by Asperger syndrome, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified (pg. 70 col. 1 para. 1); reading on claims 30-32.
Rationale for combining (MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings by Mussap, Gondalia, Pavone, Mello, Kałuzna-Czaplinska11, Bhatti, Blazenovic and West to the identification of biomarkers in the urine of autistic children as taught by Kałuzna-Czaplinska14 to initiate a timely and appropriate therapeutic treatment in a time window characterized by the development and maturation of the central nervous system (pg. 878 col. 2 para. 1 Mussap); to investigate how gastrointestinal microbiology play a role in autism (pg. 48 col. 1 para. 3 Gondalia); to investigate dysfunctional anomalies during the various steps of brain development (pg. 1 para.1 Pavone); to investigate regulation and prevention of lipid oxidative damage (pg. 154 col. 1 para. 2 Mello) in children patients (pg. 150 col. 2 para. 2 Mello); to assess biochemical and nutritional individuality in autistic children (pg. 686 Title Kałuzna-Czaplinska11); to improve neurofunctional outcome in neurological diseases such as autism (pg. 2 col. 2 para 1-3 Bhatti); to improve structure elucidation in metabolomics (pg. 13 para. 5 Blazenovick) to be used in diagnostic evidence (pg. 2 Table 1 Blazenovic); to develop metabolite profiling methods to discover biochemical pathways and mechanisms that are involved in the etiologies of ASD (pg. 11 col. 1 para. 5 West).
Regarding assigning "higher weights" to the content values of the Phenyllactic acid, the Aconitic acid, the Phosphoric acid, the 3-Oxoglutaric acid, and the Carboxycitric acid, one of ordinary skill in the art would be motivated to assign more weight to the markers most relevant to autisms to improve structure elucidation in metabolomics (pg. 13 para. 5 Blazenovick) to be used in diagnostic evidence (pg. 2 Table 1 Blazenovic) (as described by the prior art) and to achieve routine optimization towards determination of the optimum profile for the diagnosis. MPEP 2144.05 II states - The Supreme Court has clarified that an "obvious to try" line of reasoning may properly support an obviousness rejection. In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because "obvious to try" is not a valid rationale for an obviousness finding. However, in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions. 550 U.S. at 421, 82 USPQ2d at 1397 ("The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘obvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
"It is well-established that a determination of obviousness based on teachings from multiple references does not require an actual, physical substitution of elements." In re Mouttet, 686 F.3d 1322, 1332, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012). In the instant application, the use of in autism diagnosis is motivated by Blazenovick to improve structure elucidation in metabolomics (pg. 13 para. 5 Blazenovick) to be used in diagnostic evidence (pg. 2 Table 1 Blazenovic);
The prima facie case of obviousness has been established. MPEP 2141.III for "RATIONALES TO SUPPORT REJECTIONS UNDER 35 U.S.C. 103"; wherein "(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention". Furthermore, in this instant application, the amendments support existing claim rejections, in which the recited limitations are all addressed, see Claim Rejections above.
One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for investigating metabolomics and diagnostic data for autism.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 103
The Remarks of 11/25/2025 have been fully considered but are not persuasive for the reasons below:
It appears that pg. 7 para. 3 represents the only Applicant remarks specific to 103 and the instant claims (emphasis added):
The cited references, taken either alone or in combination, fail to teach or suggest at least this element [algorithm with higher weights assigned to the content values of the Phenyllactic acid, the Aconitic acid, the Phosphoric acid, the 3-Oxoglutaric acid, and the Carboxycitric acid]. For at least this reason, no prima facie case of obviousness has been established and claim 26 is allowable over the cited references.
In the claims, recitations from claims 27-29 have been added to claim 26. Claims 27-29 were rejected previously, and so all instant rejections were revised accordingly. Obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). One of ordinary skill in the art would be motivated to assign more weight to the markers most relevant to autisms to improve structure elucidation in metabolomics (pg. 13 para. 5 Blazenovick) to be used in diagnostic evidence (pg. 2 Table 1 Blazenovic) (as described by the prior art) and to achieve routine optimization towards determination of the optimum profile for the diagnosis.
"It is well-established that a determination of obviousness based on teachings from multiple references does not require an actual, physical substitution of elements." In re Mouttet, 686 F.3d 1322, 1332, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012). In the instant application, the use of in autism diagnosis is motivated by Blazenovick to improve structure elucidation in metabolomics (pg. 13 para. 5 Blazenovick) to be used in diagnostic evidence (pg. 2 Table 1 Blazenovic);
The prima facie case of obviousness has been established. MPEP 2141.III for "RATIONALES TO SUPPORT REJECTIONS UNDER 35 U.S.C. 103"; wherein "(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention". Furthermore, in this instant application, the amendments support existing claim rejections, in which the recited limitations are all addressed, see Claim Rejections above.
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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/F.F.L./Examiner, Art Unit 1685
/G. STEVEN VANNI/Primary patents examiner, Art Unit 1686