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 .
Response to Amendment
Applicant’s amendment and remarks filed on 02/05/26 have been entered. Claims 1-4, 6-13, 16, 18-20, 25, 29-30, and 34-35 were pending. Claims 20, 25, 29, and 30 remain withdrawn. Claims 1-4, 6-13, 16, 18-19, and 34-35 were under examination herein. Applicant’s amendments have overcome each and every rejection under 101 set forth in the previous Office Action mailed on 08/05/2025.
Status of Rejection
The rejection of claims 1-4, 6-13, 16, 18, 19, and 34 and 35 rejected under 101 is maintained in light of Applicant’s amendment.
The rejection of claim 2 under 103 in view of Kumar and Nardi-Agmon is withdrawn in view of Applicant’s amendment. New ground of rejection is made in view of Kumar.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/05/26 has been entered.
Claim Objections
Applicant is advised that should claim 1 be found allowable, claim 2 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 13 is objected to because of the following informalities: GCMS is recited twice as “GCMS” and “GC-MS”. Appropriate correction is required.
Claim Rejections - 35 USC § 101
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-4, 6-13, 16, 18, 19, and 34 and 35 are rejected under 35 U.S.C. 101 because the claimed invention is directed to law of nature and abstract idea without significantly more.
Regarding claim 1, 2, & 34, the claim(s) recite(s) a “method for treating a subject suffering from oesophagogastric cancer” (or a method for determining the efficacy of treating a subject suffering from the cancer); the method comprises the step of measuring and determining an increase in a level of a biomarker compound (acetic, pentanoic, butyric acid) in an endoluminal sample of a subject compare to a reference (healthy subject).
This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a law of nature in the form of a natural correlation. The claim recites detecting disease by measuring the amount of concentration of the biomarker compound in a biological sample. The amounts of biomarkers in the endoluminal sample is/are naturally correlated with diagnosing of cancer. If a claim limitation, under its broadest reasonable interpretation, covers a natural correlation, then it falls within the law of nature grouping of natural phenomena. Accordingly, the claim recites a law of nature (Step 2A, Prong 1).
This judicial exception is not integrated into a practical application. In particular, the claim recites “measuring the concentrations of a biomarker acid in an endoluminal sample” to detect/diagnose disease, which constitutes a natural correlation under broadest reasonable interpretation. There is no integration of the measurement step much less a practical one since after the measurement, a generic and broadly recited treatment step is introduced. However, the treatment step does not impose any meaningful limit since treatment being “capable of” is not particular or specific to make the claims a practical application (For example, NSAIDS or nutritional food could be considered as treatment “capable of” treating the cancer). As such, the measuring of the biomarkers is mere natural correlation that is not significantly more than law of nature. See MPEP 2106.05(g). Accordingly, this additional element does not integrate the natural correlation into a practical application because it does not impose any meaningful limits on practicing the abstract idea. The claim is directed to a judicial exception (Step 2A, Prong 2).
In addition, the claim also recites determining this level with a reference for the level of the at least one biomarker in a healthy individual, wherein an increase in the concentration of the biomarker of the test subject, compared to the reference, suggests that the subject is suffering from oesophagogastric cancer. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers an abstract idea in the form of a mental process. The claim recites comparing the amount of concentration of a biomarker in a biological sample in a sick and healthy subject and uses the comparison to determine whether or not the subject is sick. Making decision whether or not the difference of the comparison, under broadest reasonable interpretation, is a mental process that can be performed in the human mind. Nothing in the claim precludes the user from manually comparing the data of a healthy and a sick subject and deciding what would be constitute as “suggesting” the subject is suffering from the cancer. If a claim limitation, under its broadest reasonable interpretation, covers a mental process, then it falls within the mental process grouping. Accordingly, the claim recites an abstract idea (Step 2A, Prong 1).
This judicial exception is not integrated into a practical application. In particular, the claim recites suggesting that the subject is suffering the cancer if the concentration of the biomarker of interest is higher than that of a healthy subject, which constitutes a mental process under broadest reasonable interpretation. There is no integration of the diagnostic step much less a practical one since after the measurement and comparison is completed, a generic and broadly recited treatment step is introduced. However, the treatment step does not impose any meaningful limit. The diagnostics are mere mental process based on data gathered. See MPEP 2106.05(g). Accordingly, this additional element does not integrate the mental process into a practical application because it does not impose any meaningful limits on practicing the abstract idea. The claim is directed to a judicial exception (Step 2A, Prong 2).
The claim does not include additional elements that are sufficient to amount to significant more than the judicial exception. With respect to integration of the abstract idea into a practical application, the rest of the limitation, obtaining the sample during endoscopy and determining the concentration using a gas analyzer are conventional ways of data gathering. Routine and conventional data gathering cannot provide an inventive concept. The claim is not patent eligible.
Claims 3-4 and 6 do not cure the deficiency of claim 1. The claims merely recite what the sample is and how the sample is obtained from stomach or oesophagus.
Claims 7-8 and 35 do not cure the deficiency of claim 1. The claims merely recite how the sample is being obtained.
Claim 9 does not cure the deficiency of claim 1. The claim merely recites the volume of the endoluminal sample being used for the analysis.
Claim 10 does not cure the deficiency of claim 1. The claim recites the medical process of obtaining the sample (which occurs before the analysis step).
Claim 11 does not cure the deficiency of claim 1. The claim is a functional recitation of the compounds recited in claim 1.
Claim 12-13 do not cure the deficiency of claim 1. The claims merely recite the device used for detection of the biomarkers, and especially at the level of generality and with the many options of devices claimed, this does not add and particularity of measurement or detection to the claims so does not add practical application
Claim 16 does not cure the deficiency of claim 1. The claim merely recites the method can be used by analyzing more than one type of the biomarkers compounds.
Claim 18 does not cure the deficiency of claim 1. The claim merely recites the specific type of oesophagogastric cancer.
Claim 19 does not cure the deficiency of claim 1. The claim merely recites typical generic treatment for different stage of cancer that at the level of generality claimed is not particular or specific. Furthermore, the independent claim 1 do not specify how the measurement was used for determining the severity/stages of the cancer.
Claim Rejections - 35 USC § 103
Claim(s) 1-4, 6, 9, 11, 12, 13, 16, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kumar (Selected Ion Flow Tube-MS Analysis of Headspace Vapor from Gastric Content for the Diagnosis of Gastro-Esophageal Cancer, 2012) as cited in previous OA.
Regarding claims 1 and 2, Kumar discloses a method of diagnosing a subject suffering from oesophagogastric cancer, the method comprising:
Obtaining an endoluminal sample obtained from a test subject during endoscopy (A gastroscope (Olympus, Essex, UK) is introduced through the mouth and then into the esophagus; Gastric Content Sampling, pg. 9551), the level of at least one biomarker compound selected from the group consisting of acetic acid (Reproducibility and Validity of the Sampling Method, MIM Analysis of Selected VOCs in the Headspace of Gastric Content, Figure 1-2, and Table 1),
determining the concentration of the compound (By measuring the count rate of both precursor ions and the characteristic product ions at the downstream spectrometer/detection system, a real-time quantification is achieved, realizing absolute concentration of trace and volatile compounds at the parts-per-billion by-volume (ppbv) or parts-per-million by-volume level (ppmv). SIFT-MS Analysis, pg. 9551) using a gas analyzer (SIFT-MS instrument (Instrument Science, Crewe, UK; SIFT-MS Analysis, pg. 9551); and
determining the concentration of the compound in the endoluminal sample is increased relative to the concentration of the compound in a reference endoluminal sample (Two organic acids were measured using SIFT-MS in the headspace of gastric content. Acetic acid is a metabolic intermediate for the generation of the tioester acetyl-CoA. Its presence has been shown in the exhaled breath of lung cancer patients using SIFT-MS. (40) As shown in Figure 2, acetic acid in the headspace of gastric content from the cancer cohort has a higher median value and wider interquartile range, in contrast to the other 2 groups. The median value in the cancer group is found to be higher than that in the healthy group, i.e., 37 and 21 ppbv… Figure 2 shows that both the cancer and positive control groups (with higher median pH values) have higher measured concentrations of acetic acid and hexanoic acid than the healthy controls.) (Acids, Page 9554).
Kumar does not explicitly disclose a step of administering a therapeutic agent capable of treating the oesophagogastric cancer. Kumar discloses a motivation behind the study is to provide a diagnostic technique for gastro-esophageal cancer at early stage in order for people to take immediate curative treatment as most red flag symptoms occurred in a later stage as the delay only results in a lot less patients being eligible for curative treatment (In the UK, gastro-esophageal cancer remains a disease with poor patient outcomes. In 2009 in the UK, 15,656 people were diagnosed with gastro-esophageal cancer. (14) The red flag symptoms often occur at a more advanced stage of the disease, and therefore, people with such cancers most commonly go to their doctor later in the disease process. This delay in diagnosis results in only 20% of patients being suitable for potentially curative treatment at first presentation) (Introduction, Paragraph 3).
Given the method of Kumar is designed for diagnosing oesophagogastric cancer and also an increase in concentration of acetic acid content in the sample of patient compared to healthy subject, it would have been obvious to one of ordinary skill in the art to have recommended the test subject to be subjected to a treatment (administering the potentially curative treatment) if the test subject is tested with an increase in the concentration of the biomarker compared to a healthy reference.
Regarding claim 3, Kumar discloses the claimed invention as discussed above in claim 1. Kumar discloses the endoluminal sample is a gas sample (A gastroscope (Olympus, Essex, UK) is introduced through the mouth and then into the esophagus. The gastroscope is passed via the esophagus into the stomach. During this procedure, one is able to take biopsies, and fluid can also be retrieved through a suction channel within the gastroscope.) (headspace vapor)(Gas sample is taken to analyze volatile organic compounds (VOCs) (Gastric Content Sampling, pg. 9551).
Regarding claim 4, Kumar discloses the claimed invention as discussed above in claim 1. Kumar discloses the endoluminal sample comprises an oesophago-gastric endoluminal head space sample (headspace vapor) (Abstract).
Regarding claim 6, Kumar discloses the claimed invention as discussed above in claim 1. Kumar discloses the endoluminal sample is obtained from within the lumen of the stomach or oesophagus (Gastric Content Sampling, pg. 9551).
Regarding claim 9, Kumar discloses the claimed invention as discussed above in claim 1. Kumar does not explicitly disclose the volume of the endoluminal sample is at least about 50 mL. Kumar discloses that for each measurement, 10 mL of gastric content is required (For each measurement, a total of 10 mL of gastric content from the original sample jar was aliquoted into a standard 60 mL specimen jar) (SIFT-MS Analysis, pg. 9552). It would have been obvious to one of ordinary skill in the art before the effective filing date to have modified the method of Kumar by increasing the volume collected to at least 50 mL or more, doing so allows for more measurement to be done as each measurement of Kumar requires 10 mL of sample.
Regarding claim 11, Kumar discloses the invention as discussed above in claim 1. Acetic acid disclosed by Kumar is a VOC.
Regarding claim 12, Kumar discloses the claimed invention as discussed above in claim 1. Kumar discloses that at least one biomarker compound is detected using a gas analyzer (Selected Ion Flow Tube-MS Analysis).
Regarding claim 13, Kumar discloses the claimed invention as discussed above in claim 1. Kumar discloses that at least one biomarker compound is detected using a mass spectrometry (Selected Ion Flow Tube-MS Analysis).
Regarding claim 16, Kumar discloses the claimed invention as discussed above in claim 1. Kumar discloses that acetic acid is determined (Figure 2d).
Regarding claim 18, Kumar discloses the claimed invention as discussed above in claim 1. Kumar discloses the cancer is gastric or oesophageal cancer (Abstract).
Claim(s) 7-8 and 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kumar in view of Leja (Ex vivo emission of volatile organic compounds from gastric cancer and non-cancerous tissue, 2018) as cited in previous OA.
Regarding claims 7-8 and 35, Kumar discloses the claimed invention as discussed above in claim 1. Kumar does not explicitly disclose the endoluminal sample is obtained adjacent to a tumour or suspected location of a tumour within the distance claimed (claim 8 and 35).
In an analogous art, Leja discloses analyzing emission of volatile organic compounds from gastric cancer and non-cancerous tissues (Comparison of VOCs emitted from gastric cancer tissue to those emitted from non-cancerous tissue would help in understanding which of the VOCs are associated with gastric cancer and provide a deeper knowledge on their generation.) (Abstract) Leja discloses there is significant difference in concentration of analyte of interest between cancerous and non-cancerous tissues.
Based on Leja’s disclosure, it would have been obvious to one of ordinary skill in the art before the effective filing date to have extracted endoluminal sample near tumour or suspected tumour in order to determine any abnormal reading in VOCs emission for diagnosis of gastric cancer.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kumar in view of Ganatra (Carbon Dioxide versus Air Insufflation in Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, 2017) as cited in previous OA.
Regarding claim 10, Kumar discloses the claimed invention as discussed above in claim 1. Kumar does not explicitly disclose the method comprises inflating the stomach with medical air, and then advancing a sampling tube for obtaining the endoluminal sample into the subject’s lumen of the stomach during endscopy.
Ganatra discloses inflating the stomach with medical air is commonly used for gastric carcer diagnosis (Background/Aims, Introduction, Ganatra) (Endoscopic submucosal dissection (ESD) with air insufflation is commonly used for the staging and treatment of early gastric carcinoma.).
It would have been obvious to one of ordinary skill in the art before the effective filing date to have uses standard medical method for gastric disease diagnosis such as inflating stomach with medical air. Inflating the stomach allows for easier sampling and detection during endoscopy.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kumar in view of Hwang (Endoscopic resection of gastric and esophageal cancer, 2015) as cited in previous OA.
Regarding claim 19, Kumar discloses the claimed invention as discussed above in claim 1. Modified Kumar does not explicitly disclose the treatment. In an analogous art, Hwang discloses the endoscopic resection of gastric and esophageal cancer for early-stage cancer as the treatment is relatively minimally invasive compared to treatment of later stage cancer (Abstract). Therefore, it would have been obvious to one of ordinary skill in the art to have suggested treatment such as the one by Hwang for treatment of early-stage cancer.
Claim(s) 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kumar in view of Samson (Biologic therapy in esophageal and gastric malignancies: current therapies and future directions, 2017) as cited in previous OA.
Regarding claim 34, Kumar discloses the claimed invention as discussed above in claim 1. Kumar does not explicitly disclose using a therapeutic agent (interpreted as substance treatment) of treating oesophagogastric cancer.
In an analogous art, Samson discloses a list of drugs capable of treating oesophagogastric cancer such as trastuzumab (Abstract). Therefore, it would have been obvious to one of ordinary skill in the art to have suggested treatment such as trastuzumab, which is recommended by the National Comprehensive Cancer Network (NCCN), for patient diagnosed with esophagogastric cancer.
Response to Arguments
Applicant’s arguments, see Pages 7-9, filed on 02/05/26, with respect to the amendment to claims 1-4, 6-13, 16, 18, 19, and 34 and 35 have been fully considered and are persuasive. The 101 rejection of claims 1-4, 6-13, 16, 18, 19, and 34 and 35 has been maintained in light of Applicant’s amendment, for the reasons as shown in the above rejection.
Further with respect to the 101 rejection, regarding the first argument directed to Step 2A-Prong 1, applicant amends the claims to introduce limitation such as obtaining an endoluminal sample during endoscopy, determining the concentration of the compound using a gas analyzer, and administering a therapeutic agent capable of treating the oesophagogastric cancer. Applicant argues that these limitations are not directed to a law of nature and abstract idea. Examiner agrees that these steps are not directed to a law of nature and abstract idea explicitly. However, the claim also includes a step of “determining the concentration of the compound in the endoluminal sample is increased relative to the concentration of the compound in a reference endoluminal sample”. The step is directed to both law of nature and a mental process as discussed in the 101 rejections in this Action. The step of determining concentration increase, as recited, does not preclude the method from being practice in the human mind. For example, as recited, the step can permit one to read and compare the result output by gas analyzer to the reference concentration and make decision of administering therapeutic agent in the event the compound concentration in patient is higher than a reference. Therefore, the claims still contain elements directed to abstract idea in accordance to Step 2A-Prong 1.
Regarding the second argument directed to Step 2A-Prong 2, applicant’s amendment introduces limitation of collecting sample during endoscopy and determining concentration using gas analyzer. Applicant argues, the claims, as drafted, require particular machine that is integral to the claim(s).
MPEP 2106.05(b) states “Integral use of a machine to achieve performance of a method may integrate the recited judicial exception into a practical application or provide significantly more, in contrast to where the machine is merely an object on which the method operates, which does not integrate the exception into a practical application or provide significantly more” (II) and “Use of a machine that contributes only nominally or insignificantly to the execution of the claimed method (e.g., in a data gathering step or in a field-of-use limitation) would not integrate a judicial exception or provide significantly more” (III).
In this instance, the generically claimed endoscope and gas analyzer is merely an “object” on which the method operates (i.e. collecting gastric sample and determining the concentration based on sample collected). Furthermore, endoscopes are well-known medical procedure for examining internal organs, primarily the digestive tract. Therefore, at best, the claimed limitations, as drafted, are conventional data gathering and processing that do not integrate the judicial exception into a practical application.
Regarding applicant’s argument directed to Step 2B, applicant argues the determining the concentration of compounds including acetic acid, butyric acid and pentanoic acid to guide treatment for oesophagogastric cancer in order to achieve improved efficacy or safe is not routine or conventional treatment. Applicant cites Intellectual Ventures I v. Symantec Corp, Synopsys, Inc. v. Mentor Graphics Corp., and BASCOM Global Internet v. AT and T Mobility LLC for support.
In Mayo Collaborative Services (2012), the Supreme Court held that the contested diagnostic claims were unpatentable for “effectively claim[ing] the underlying laws of nature themselves.” The claims at issue discloses a method of:
Administering thiopurine drugs;
Measuring the patient’s resulting thiopurine metabolite levels; and
Adjusting the dosage based on the resulting levels.
The Court held that the claims were unpatentable because they are directed to the underlying natural relationship between thiopurine drug metabolism and thiopurine metabolite levels, without involving any inventive or unconventional concepts. Similarly, the current claim involves assessing the efficacy of a generic treatment “capable of” treating the cancer by measuring the patient’s resulting at least one of the three claimed biomarkers levels without involving any inventive or unconventional concepts. Therefore, the rejection of the claims under 101 are maintained.
Applicant's arguments, see Pages 9-11, filed on 02/05/26, with respect to the 103 rejections of claims 1-4, 6-13, 16, 18, 19, and 34 and 35 have been fully considered but they are not persuasive.
Regarding the argument of directed toward embodiment of butyric acid and pentanoic acid on page 10 of the remark, Examiner notes that in a claim that recites “selecting a compound” from a list of alternatives, the prior arts only need to anticipate or render obvious one of the embodiments for the whole claim to be rejected. At the time of the prosecution, the issue is specifically directed to prior arts teaching the method using the embodiment of acetic acid.
Regarding applicant’s directed toward embodiment of acetic acid, Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references. Furthermore, Applicant's arguments do not comply with 37 CFR 1.111(c) because they do not clearly point out the patentable novelty which he or she thinks the claims present in view of the state of the art disclosed by the references cited or the objections made. Further, they do not show how the amendments avoid such references or objections.
Applicant argues the increase in acetic acid concentration in the headspace of gastric content in the cancer group and that in the healthy group are not “statistically different” even though Kumar discloses a trend of general increase of acetic acid in cancer group relative to healthy group. However, the claim does not incorporate any elements the applicant utilized in order to improve the differences in acetic acid concentration such that differences “statistically different”. Even though Kumar establishes certain metabolites other than acetic acid may be better at serving as biomarkers for analyzing the cancer, nevertheless Kumar discloses the difference in acetic acid content that would have enabled one of ordinary skill in the art to develop a cancer diagnosis/treatment method using acetic acid as a possible marker.
It is noted that the IDS filed 05/16/2025 has been considered and is attached.
Conclusion
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/M.H./Examiner, Art Unit 1758
/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758