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 2, 5, 14, 15, 17, 21-24, 26-28, and 31-34 were cancelled. Claims 20, 25, 29, and 30 remain withdrawn from consideration. Claims 1, 3, 4, 6-13, 16, 18, 19, 35 are examined herein. Applicant’s amendment and remark have overcome each and every objection set forth in Office Action mailed on 02/12/26.
Status of Objection and Rejection
The rejection of claims 1, 3-4, 6-13, 18-19, and 35 rejected under 101 is maintained.
The rejection of claim 2 is obviated by Applicant’s cancellation.
The objection of claim 13 is withdrawn in view of Applicant’s amendment.
The amendment necessitates new ground of rejection.
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, 3-4, 6-13, 16, 18, 19, and 35 are rejected under 35 U.S.C. 101 because the claimed invention is directed to law of nature without significantly more.
Regarding claim 1, the claim(s) recite(s) a “method for treating a subject suffering from oesophagogastric cancer”; the method comprises the step of measuring and determining an increase in a level of two biomarker compounds (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/determining the concentrations of biomarker acids 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 after detecting an increase is introduced. However, the treatment step does not impose any meaningful limit since treatment 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).
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 and administering therapy/therapeutic agent if an increase is detected are conventional ways of data gathering and medical treatment procedure. Routine and conventional data gathering and medical procedure 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 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, 3-4, 6, 9, 11, 13, 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 in view of Markar (Breath Test Might Help Detect Stomach and Esophageal Cancers, 2017).
Regarding claim 1, 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 disclose a second and/or third compound selected from the group consisting of butyric acid and pentanoic acid are being measured and determined. Furthermore, Kumar does not explicitly disclose a step of administering a therapeutic agent capable of treating the oesophagogastric cancer.
Regarding measurement of a second and/or third compound selected from the group consisting of butyric acid and pentanoic acid. Markar discloses a method of sampling for butyric and pentanoic acids (The trial was based on the results of previous research that suggested differences in the levels of specific chemicals (butyric, pentanoic and hexanoic acids; butanal; and decanal) between patients with stomach or esophageal cancer and patients with upper gastrointestinal symptoms without cancer. Para. 4) using ion flow-tube mass spectrometry by collecting breath samples from hospital patients with half of the patients diagnosed with stomach or esophageal cancer and the other half showed no evidence of cancer (Study Finding, para. 1). The test results have an 85% accuracy (Study Findings, para. 3). Markar states “Because cancer cells are different from healthy ones, they produce a different mixture of chemicals. This study suggests we may be able to detect these differences and use a breath test to indicate which patients are likely to have cancer of the esophagus and stomach and which do not…” Study Findings, para. 4).
It would have been obvious to one of ordinary skill in the art before the effective filing date to have incorporated additional testing for pentanoic and butyric acids using ion flow-tube mass spectrometry in the method of Markar to the method of testing for acetic acid in the method of Kumar to derive the claimed invention with predictable results that the concentration of these markers were expected to be higher in the breathe sample of the cancer patients as taught by the respective authors.
Regarding claim limitation of administering therapeutic agent, 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 and Markar are designed for diagnosing oesophagogastric cancer by recognizing an increase in concentration of acetic, butyric, and pentanoic 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, Modified 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, Modified 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, Modified 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, Modified 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, Modified Kumar discloses the invention as discussed above in claim 1. Acetic acid disclosed by Kumar and butyric and pentanoic acid disclosed by Markar are VOCs.
Regarding claim 13, Modified Kumar discloses the claimed invention as discussed above in claim 1. Kumar discloses that at least two compounds are detected using a mass spectrometry (Selected Ion Flow Tube-MS Analysis).
Regarding claim 18, Modified 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 Markar as discussed above in claim 1, and further 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, Modified Kumar discloses the claimed invention as discussed above in claim 1. Neither Kumar nor Markar explicitly discloses 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 Markar as discussed above in claim 1, and further 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, Modified Kumar discloses the claimed invention as discussed above in claim 1. Neither Kumar nor Markar explicitly discloses 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 endoscopy.
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) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kumar in view of Markar as discussed above in claim 1, and further in view of Wilson (Application of Electronic-Nose Technologies and VOC-Biomarkers for the Noninvasive Early Diagnosis of Gastrointestinal Diseases, 2018).
Regarding claim 12, Modified Kumar discloses the claimed invention as discussed above in claim 1. Neither Kumar nor Markar discloses the gas analyzer is an electrochemical sensor, a semiconducting metal oxide sensor, a quartz crystal microbalance sensor, an optical dye sensor, a fluorescence sensor, a conducting polymer sensor, a composite polymer sensor, or optical spectrometry.
In an analogous art, Wilson discloses application of using electronic-nose (e-nose) (which can be electrochemical, a semiconducting metal oxide, conducting polymer, quartz crystal microbalance, a fluorescence sensor, or an optical spectrometry) for noninvasive early diagnosis of gastrointestinal (GI) disease by sampling VOCs (Abstract). Wilson discloses e-nose can be a portable substitute for the SIFT-MS for sampling VOCs for early diagnosis of GI disorder (para. 3, 2.2. New Metabolomic Disease-Detection Approaches; Introduction, para. 2).
Generally, making a device/method portable is not patentably distinguish over an otherwise old device/method unless there are new or unexpected results. See MPEP 2144, V, A, In reLindberg, 194 F.2d 732, 93 USPQ 23 (CCPA 1952) (Fact that a claimed device is portable or movable is not sufficient by itself to patentably distinguish over an otherwise old device unless there are new or unexpected results.). It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute e-nose in place of SIFT-MS to develop a portable and less-time consuming and cheaper method for measuring VOCs and using the results for diagnosis (Wilson, para. 3, 2.2. New Metabolomic Disease-Detection Approaches; Introduction, para. 2).
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kumar in view of Markar as discussed above in claim 1, and further in view of Hwang (Endoscopic resection of gastric and esophageal cancer, 2015) as cited in previous OA.
Regarding claim 19, Modified 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.
Response to Arguments
Applicant’s arguments with respect to 103 rejection of claim(s) 1, 3-4, 6-13, 18-19, and 35 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Regarding applicant’s argument for Step 2A-Prong 2 analysis, applicant argues that the claim method now recites implementation of a particular machine by using a “gas analyzer”. MPEP 2106.05(b)-I states “The particularity or generality of the elements of the machine or apparatus, i.e., the degree to which the machine in the claim can be specifically identified (not any and all machines). One example of applying a judicial exception with a particular machine is Mackay Radio & Tel. Co. v. Radio Corp. of America, 306 U.S. 86, 40 USPQ 199 (1939). In this case, a mathematical formula was employed to use standing wave phenomena in an antenna system. The claim recited the particular type of antenna and included details as to the shape of the antenna and the conductors, particularly the length and angle at which they were arranged. 306 U.S. at 95-96; 40 USPQ at 203.” In Parker v. Flook discloses that the that the mechanical implementation of a natural principle must be "inventive". In the claim’s current form, the machine as claimed is generically claimed as a gas analyzer without specifying any distinctive elements that may allow the machine to be considered as “particular”.
Section II 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.” As such, the Examiner considered the gas analyzer, as drafted, as merely an object on which the method (i.e. determining an law of nature correlation) operates, which does not integrate the exception into the practical application.
Regarding applicant’s second argument with respect to Step 2B, applicant argues the method comprises administration of a therapeutic agent to test subject with a particular level of at least two compounds in a sample, and therefore, possess the inventive concept in terms of subject matter eligibility determination. First, the correlations between the claimed VOCs and likelihood of oesophagogastric cancer is known or can be ascertained by one of ordinary skill in the art (See prior art rejection above). Second, the claim recites the additional element of “administering a treatment to the patient having an increased in concentration in the at least two compounds”. Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is. Instead, the limitation covers any possible treatment that a doctor decides to administer to the patient, making the limitation’s inclusion in this claim at best nominal.
For the reason above, the 101 rejection is respectfully maintained.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Breath volatile organic compound analysis for the diagnosis of oesophago-gastric cancer; multi-centre blinded validation clinical trial, 2017 is a submitted abstract by Markar and one of the inventors for European Cancer Congress cited in the article by Markar.
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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/M.H./ Examiner, Art Unit 1758
/REBECCA M FRITCHMAN/ Primary Examiner, Art Unit 1758
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