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 16/766956 RCE filed 12/01/2025.
Claims 1, 6-7, 11-14, 18, 20-21, 25, & 28 are pending and have been examined and fully considered.
Claims 2-4, 8-10, 15-17,19, 22-24, & 26-27 are cancelled.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/01/2025 has been entered.
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 1, 6-7, 11-14, 18, 20-21, 25, and 28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract idea without significantly more.
Step 1: Claim 1 is directed towards a method.
Step 2A, Prong One: Claim 1 recites the abstract idea, “(iii) comparing the concentration of the signature compound in the bodily sample from the subject with a reference for the concentration of the signature compound in an individual who does not have the oesophago-gastric cancer...” Abstract human reasoning or a generic computer is required to compare the concentration of the signature compound with a reference.
Claim 1 recites the law of nature of a natural correlation, “increase in the concentration of the signature compound (which is one compound from groups list in Claim 1 from groups i, ii, or iii) in the bodily fluid sample from the subject compared to the reference indicates that the subject has the cancer.”
The fact that the claimed “signature compound,” are produced from substrates which are “metabolized by a cancer -associated bacterium into a signature compound,” does not change this matter as the comparison is still an abstract idea and natural correlation. Further—the “substrates,” are compounds which can be ingested naturally in a person’s diet.
Step 2A, Prong Two: The claimed judicial exceptions are not integrated into a practical application because upon detecting the concentration of the signature compound in the bodily sample and comparing the concentration of the signature compound with a reference, no particular and specific practical application occurs. In claim 1, in step (iv), it is claimed that various therapies are carried out “when,” the patient has a particular stage of the disease. However--- as detailed in the 112 rejection below—no guidance is given for how one would know when a person has a particular stage of the disease.
It is not guaranteed in the claim language that a patient for sure has one of the differentially diagnosed cancers that the claimed generalized cancer treatments are claimed for (resectable oesophago-gastic cancer, early stage oesophago-gastric cancer, or advanced oesophago-gastric cancer), but only that the level of signature compound is assayed for. Further, the claimed treatments for these cancers including palliative chemotherapy and surgery do not seem specific for oesophago-gastric cancer, but instead for all cancers of a particular stage.
Further- for each differential diagnosis stage, which can also include no differential diagnosis, and just further diagnosis which the claim has already started with---see in claim 1, after step c) the line starting with “administering,” the claimed “therapeutic agent capable of treating,” is also not considered to be particular and specific treatment, and therefore the claimed treatments are not a practical application of the claimed judicial exceptions.
Treatment with the claimed “therapeutic agent capable of treating,” is akin to “administering a suitable medication.”
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.”
To properly integrate the judicial exception under the treatment and prophylaxis consideration, the claim should be amended to recite specific chemotherapies, chemoradiotherapies, surgeries, endoscopic resections, and therapeutic agents specific to the claimed oesophago-gastric cancer.
Further see MPEP 2106.04.a:
a. The Particularity Or Generality Of The Treatment Or Prophylaxis
“The treatment or prophylaxis limitation must be “particular,” i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). The claim also recites “administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype.” This administration step is particular, and it integrates the mental analysis step into a practical application. Conversely, 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.
Examiners may find it helpful to evaluate other considerations such as the mere instructions to apply an exception consideration (see MPEP § 2106.05(f)), and the field of use and technological environment consideration (see MPEP § 2106.05(h)), when making a determination of whether a treatment or prophylaxis limitation is particular or general.”
Also see Vanda memorandum.
With respect to the instantly claimed—step i) in Claim 1, the claimed administering is done before the instant judicial exception is performed. There this is extra-solution activity as does nothing to practically apply the judicial exception as it is performed before the judicial exception in the claims.
For step ii) in Claim 1, the generally claimed “detecting,” is done as just a data-gathering to perform the judicial exception and therefore is also insignificant extra-solution activity that does nothing to practically apply. See MPEP 2106.05 (g).
Step 2B: Claim 1 recites the elements “(i) administering to the subject a composition comprising one or more substrate… wherein the one or more substrate is metabolized by a cancer-associated bacterium into a signature compound,” “(ii) detecting, in a bodily sample from the subject, the concentration of the signature compound.”
These elements are interpreted as extra-solution activity which are incidental to the primary process and are mere data gathering which is not considered significantly more than the abstract idea or law of nature (see MPEP § 2106.05(g), Insignificant Extra-Solution Activity). Even further- glucose, tyrosine, glutamic acid, and glycerol the claimed substrates which are administered in Claim 1, step i) are all things which can be ingested through a humans diet on a regular basis so they are considered well understood, routine and conventional (WURC) and therefore are not enough to add significantly more to the claims.
Claim 1 further recites the elements:
“(iv) carrying out on the subject:
(a) neoadjuvant chemotherapy, or chemoradiotherapy followed by surgery and adjuvant chemotherapy, when the subject has resectable oesophago-gastric cancer
(b) endoscopic resection when the subject has early stage oesophago-gastric caner
(c) palliative chemotherapy when the subject has advanced oesophago-gastric cancer, or
administering a therapeutic agent capable of treating the oesophago-gastric cancer to the subject whose concentration of the signature compound in the bodily sample indicates that the subject has the cancer, thereby treating the cancer in the subject.”
Reciting neoadjuvant chemotherapy, chemoradiotherapy, surgery, adjuvant chemotherapy, endoscopic resection, palliative chemotherapy, chemotherapy, chemoradiotherapy with or without surgery, endoscopic resection, or administering a therapeutic agent capable of treating the cancer to the subject thereby treating the cancer, is neither particular nor specific because the terms are generic to all of these claimed treatments are used for all types of cancers, not just the claimed oesophago-gastric cancer recited
Each of the cited treatment and prophylaxis elements above require more specific treatments/surgeries in order to treat one of the oesophago-gastric cancer because one chemotherapy, chemoradiotherapy, surgery, endoscopic resection, or therapeutic agent may be appropriate for one type of patient exhibiting different symptoms and with a different measured level of signature compound, but may not be appropriate for another, yet the claim is completely silent on any specifics. The claim merely attempts to integrate the judicial exception by reciting generic treatment and prophylaxis limitations and this is not successful. As claimed, these treatments are all considered WURC in the art and therefore do not add significantly more to the instant claims. See MPEP 2106.05(d) II.
The dependent claims are analyzed the same way as the independent claim.
Claims 6-7, 11-14, 18, 20-21, 25, and 28 recite elements that further limit the cited elements of claim 1 above, but are directed towards elements which are interpreted as extra-solution activity which are incidental to the primary process and are mere data gathering which is not considered significantly more than the abstract idea (see MPEP § 2106.05(g), Insignificant Extra-Solution Activity). These include that the composition administered can be ingested and is something like glucose (sugar) or specific amounts of the substrates administered (again, which can be ingested naturally in a human diet), what the bacterium which is in the human body might be (a natural compound) which does not change the 101 interpretation since still a natural composition/bodily fluid or humans breath sample is measured. As such, these claims are rejected as being dependent upon rejected claim 1 as they do nothing to practically apply at step 2A, 2, nor do they do anything to add significantly more at step 2B.
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, 6-7, 11-14, 18, 20-21, 25, & 28 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 amendments made 07/24/2025 (so, prior to the instantly filed 12/01/2025 response) are unclear. The rejection with respect to this was also pointed out in the last office action (Final action dated 07/31/2025).
Specifically with respect to Claim 1, it is unclear how one would know when the patient has “resectable oesophago-gastric cancer,” “early stage oesophago-gastric cancer,” or “advanced stage oesophago-gastric cancer.” As claimed, the comparison to a reference only points out that if the signature compound measured is increased compared to a reference, then the patient has “the cancer,” which when referring back to the preamble of the claim means “oesophago-gastric cancer.”
The claim does not lay out how/if any differential diagnosis is performed, but only gives very general guidelines for overarching “cancer.” Therefore, it is also unclear how one would determine if any of the claimed treatments would be carried out or not as they are only performed conditionally, “when,” the patient has a specific subtype of cancer (resectable oesophago-gastic cancer, early stage oesophago-gastric cancer, or advanced oesophago-gastric cancer, or no differential diagnosis of just oseophago-gastric cancer).
Even further for Claim 1, after step iv), it is claimed, “administering a therapeutic agent capable of treating the cancer.” Since iv) includes a listing of a few differential diagnosis stages of cancer--- it is not clear what “the cancer” is referring back to in the last line of the claim and therefore it has improper antecedent basis. Correction is required.
This issue is also present in Claim 1, step iii), line 3 & 5, when “the cancer,” is used--- but it is not specified if it is the same “oesophago-gastric cancer,” recited in the preamble or not, and therefore the terms, “the cancer,” fail to have proper antecedent basis. Applicant should scan the claims for other instances where just “cancer,” or “the cancer,” is used and make it clear in the claim language what type of cancer they are referring to in all instances.
Even further for Claim 1, step i), “the substrates,” in lines 1 & 2 fail to have proper antecedent basis as “substrates,” were not mentioned in the claim priorly, so it is unclear what “the,” refers back to.
With respect to Claim 6, “which is suitable,” is unclear in the claim. The term “suitable” is a relative term which renders the claim indefinite. The term “suitable” 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. Different people would think different things are “suitable,” for metabolism, as claimed and therefore it is unclear what this term means in the claim.
With respect to Claim 7, “that is designed to,” and “certain,” are unclear in the claim. The “designed to,” indicates that the substrate isn’t already able to degrade as claimed, making it unclear in the claim. Further, “certain,” is a relative term, which would mean different things to different people, and therefore is unclear in the claim.
The rest of the dependent claims are rejected by virtue of being dependent 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, 6, 11-14 & 28 are rejected under 35 U.S.C. 103 as being unpatentable over PRINGLE in US 20180103935 in view of SPANEL in Quantification of trace levels of the potential cancer biomarkers formaldehyde, acetaldehyde and propanol in breath by SIFT-MS," cited in prior action) and further in view of SOHRABI in Volatile Organic Compounds as Novel Markers for Detection of Bacterial Infections (cited in prior action).i and further in view of JP 4698843.
With respect to Claim 1, PRINGLE teaches of a method of analysis by mass spectrometry (abstract). PRINGLE teaches that the method is used for accurate diagnosis and tissue characterization of cancers (paragraph 0006), and that gastro-intestinal cancers are a leading cause of mortality and account for 23 % of cancer related deaths (paragraph 0004). PRINGLE teaches that the sample that is analyzed can be taken from the oesophagus (paragraph 0139, 0281, 0306) or from gastric mucosa (paragraph 0166). PRINGLE teaches that these cancers can come from bacterial infections and the bacterial markers can be useful for rapid and robust diagnosis of cancers and specifically in oesophageal models (paragraph 0423) and that the bacteria species specifically can be clostridium difficile (paragraph 0454) and further that the samples can detect metabolites of the biomarkers or samples (paragraph 0013, 0423). PRINGLE further teaches that a compound can be administered to the patient in question which is a drug which can contain tyrosine (paragraphs 0481-0483), and further teach that the drug treatment may also include chemotherapy as claimed (paragraph 0515). PRINGLE further teach of comparison of a biomarker to a reference and an increase or decrease with respect to a healthy control indicates disease (paragraph 0548, 0576-0578).
However, PRINGLE does not teach of detecting the claimed signature compounds and specifically the signature compounds in in comparison with a reference for the concentration of the signature compound in an individual who does not suffer from the cancer, wherein an increase or a decrease in the concentration of the signature compound compared to the referenc
SPANEL is used to remedy this and discloses detecting cancer biomarkers including formaldehyde, acetaldehyde and propanol (abstract). SPANEL teaches that comparing the levels of biomarkers between an individual suspected of having cancer and a healthy control enables differentiation between a healthy subject and a cancerous subject and enhanced amounts of certain biomarkers in the breath of cancer patients reveals potential biomarkers specific to cancers such as tumors (p. 2, col. 2, para. 3 – p. 3, col. 1, para. 1).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the disclosure of PRINGLE to include comparing the concentration of the signature compound with a reference for the concentration of the signature compound in an individual who does not suffer from cancer, wherein an increase or a decrease in the concentration of the signature compound compared to the reference, indicates that the subject is suffering from the cancer for the benefit of differentiating between a healthy subject and a cancerous subject (SPANEL: p. 2, col. 2, para. 3 – p. 3, col. 1, para. 1)
PRINGLE and SPANEL do not teach of a method wherein the signature compound is a volatile organic compound (the claimed signature compounds) produced from bacteria.
SOHRABI teaches a method of detecting bacterial infection by means of biomarkers in the form of volatile organic compounds (VOCs) (abstract). SOHRABI further teaches that bacterial VOCs provide sensitive and specific biomarkers for bacterial detection in human specimens and culture media (abstract). SOHRABI further teaches a method wherein the volatile organic compound (VOC) is selected from a group consisting of: acetic acid, ethanol, acetone, acetic acid, phenol, or acetaldehyde (SOHRABI: see Table 1, p. 2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify PRINGLE and SPANEL to further include wherein the signature compound is a volatile organic compound (VOC) for the benefit of providing a sensitive and specific detection of bacterial detection in human specimens (Sohrabi: abstract).
PRINGLE, SPANEL, and SOHRABI do not teach of administration of a composition which contains glucose, glycerol, tyrosine, and glutamic acid.
JP 4698843 is used to remedy this. JP 4698843 teaches of methods of detecting a monitoring uptake of bioactive agents by cells (title and abstract). JP 4698843 further teaches providing compositions for increasing cellular uptake of bioactive agents (paragraphs 0005). JP 4698843 further teaches that the composition can include glucose and glycerol (paragraph 0006), tyrosine, glutamic acid, and glutamine (paragraph 0009, 0049, 0053).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to provide a composition including tyrosine, glutamic acid, glutamine, glucose, and glycerol as is done in JP 4698843 in the methods of PRINGLE, SPANEL, and SOHRABI, due to the need in the art for better methods of increasing and measuring cellular uptake of compositions into cells (JP 4698843, paragraph 0004).
With respect to Claim 6, PRINGLE teaches that a compound can be administered to the patient in question which is a drug which can contain tyrosine (paragraphs 0481-0483), and further teach that the drug treatment may also include chemotherapy (paragraph 0515).
With respect to Claim 11, PRINGLE teaches of the bacterium being part of the microbiome of the subject (paragraph 0067, 0184).
With respect to Claim 12, PRINGLE teaches of the bacterium being streptococcus (paragraph 0402).
With respect to Claim 13, PRINGLE teaches of the bacterium being s. pyrogenes (paragraph 0454).
With respect to Claim 14, PRINGLE teaches of the bacterium being s. pyrogenes (paragraph 0454).
With respect to Claim 28, SPANEL teaches of the sample being breath (abstract).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over PRINGLE in US 20180103935 in view of SPANEL in Quantification of trace levels of the potential cancer biomarkers formaldehyde, acetaldehyde and propanol in breath by SIFT-MS," cited in prior action) and further in view of SOHRABI in ("Volatile Organic Compounds as Novel Markers for Detection of Bacterial Infections," 28 May 2014, cited in prior action) in view of JP 4698843 and further in view of PAN in WO 2004/006766(as cited on prior action).
With respect to Claim 7, modified PRINGLE in view of SPANEL in view of SOHRABI in view of JP 4698843 teaches of the method as shown above, but does not teach a method wherein the composition comprising the at least one substrate is: (i) in the form of a capsule that is designed to degrade at a certain position with the gastrointestinal tract, thereby offering targeted release.
PAN however discloses a method wherein the composition comprising the at least one substrate is: (i) in the form of a capsule that is designed to degrade at a certain position with the gastrointestinal tract, thereby offering targeted release of the at least one substrate (A preferred optional component is one which delays gastric emptying, thereby increasing the length of time that the administered urea is present in the stomach) (Pan: [0038]); or (ii) is a solid (solid tablets or capsules), fluid or liquid (liquid solutions or emulsions), which is swallowed (oral ingestion of urea) (Pan: [0038]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have patient orally ingest the substrate as is done in PAN in the methods of PRINGLE, SPANEL and SOHBRABI due to the advantage this offers for targeted release (Pan, paragraph 0038).
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over PRINGLE in US 20180103935 in view of SPANEL in Quantification of trace levels of the potential cancer biomarkers formaldehyde, acetaldehyde and propanol in breath by SIFT-MS," cited in prior action) and further in view of SOHRABI in ("Volatile Organic Compounds as Novel Markers for Detection of Bacterial Infections," 28 May 2014, cited in prior action), in view of JP 4698843 in view of KARASEVA in (RU 2472445, published 20 January 2013, cited from the English translation provided by Espacenet and paragraph numbers inserted for citation, cited in prior action),i
With respect to Claim 25, PRINGLE in view of SPANEL in view of SOHRABI and in view of JP 4698843 is silent on a method wherein the composition comprises the compositions recited in the amount claimed by claim 25.
KARASEVA discloses the analogous art of clinical diagnostics of stomach cancer (para. 1.). KARASEVA teaches that cancer cells actively break down glucose and release lactic acid and therefore glucose may be administered as a substrate that can be used to detect the presence of cancer cells given that bacteria metabolize the glucose and produce a detectable metabolite, lactic acid, in a much higher concentration than in the absence of a cancerous process in the stomach (para. 20). KARASEVA further recognizes the concentration of glucose as a result-effective variable which produces a desired amount of metabolite (20 ml of a 40% solution of glucose is used as a test load to increase the formation of lactic acid) (para. 21.).
MPEP §2144.05 Part II Subpart B defines a result-effective variable as a variable which achieves a recognized result and which its optimal or workable ranges might be discovered through routine experimentation. Further, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the result-effective variable of glucose concentration to be at a concentration of about 7000mg/100mL and 20000mg/100mL, or between about 9000mg/100mL and 17000mg/100mL, or between about 11000mg/100mL and 15000mg/100mL, for the benefit of producing a desirable amount of detectable metabolite (KARASEVA: para. 21.) and detecting cancer (KARASEVA: para. 20).
Claims 18 & 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over PRINGLE in US 20180103935 in view of SPANEL in Quantification of trace levels of the potential cancer biomarkers formaldehyde, acetaldehyde and propanol in breath by SIFT-MS,") and further in view of SOHRABI ("Volatile Organic Compounds as Novel Markers for Detection of Bacterial Infections," 28 May 2014),i in view of JP 4698843 and further in view of Buszewski in "Identification of volatile organic compounds secreted from cancer tissues and bacterial cultures," 03 May 2008, as cited in prior action) Meng is relied upon as an evidentiary reference demonstrating the association between different cancers and different bacterial strains was known before the effective filing date of the claimed invention and the claimed priority date of 27 November 2017, as cited in prior action.
Regarding claims 18 & 20-21, modified PRINGLE in view of SPANEL in view of SOHRABI in view of JP 4698843 teach of the invention as shown above but is silent on methods wherein the cancer is as recited by claims 18 & 20-21, wherein the composition comprises a substrate which is as recited by claims 18 & 20-21, which is metabolized to a signature compound as recited by claims 18 & 20-21, optionally which is analyzed to indicate the presence of bacterial microorganisms as recited by claims 18 & 20-21.
Buszewski discloses the analogous art of determination of volatile organic compounds (VOCs) excreted by stomach tissue and bacteria culture (abstract). Buszewski teaches that bacteria may cause carcinogenic changes in cells and characterizing volatile organic compounds (VOCs) in the breath of patients enables non-invasive, painless, and sensitive diagnosis of many cancers such as lung, breast, and gastric cancers (p. 89, col. 1, para. 2) and places patients on a path for treatment (p. 93, col. 2, para. 2). Buszewski further teaches that said VOCs are generated during metabolic processes of bacteria (p. 88, col. 2, para. 4 bridging to p. 89) and that by studying the VOC profiles, a pathological state may be established (p. 93, col. 1, para. 5 to col. 2, para. 1).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the combination of PRINGLE in view of SPANEL in view of SOHRABI in view of JP 4698843 to include a method wherein the composition comprises a substrate as recited according to one of claims 18 & 20-21, which is metabolized to a signature compound (corresponding to said recited substrate according to one of claims 18 & 20-21), by performing routine experimentation or optimization to select the specific signature compound (VOC) that corresponds to the carcinogenic bacteria (Buszewski: p. 88, col. 2, para. 4 bridging to p. 89) of the particular type of cancer recited by claims 18-21, which would also require optionally analyzing the presence of bacterial microorganism of interest, for the benefit of enabling non-invasive, painless, and sensitive diagnosis of many cancers such as lung, breast, and gastric cancers (Buszewski: p. 89, col. 1, para. 2) and placing patients on a path for treatment (Buszewski: p. 93, col. 2, para. 2).
Meng provides evidence that specific associations between cancers and bacterial strains was known before the effective filing date of the claimed invention and the priority date of 27 November 2017: Esophageal squamous cell carcinoma (ESCC) and Firmicutes (Lactobacillus acidophilus); and Barrett’s esophagus and Enterobacteriaceae (Klebsiella pneumoniae) (Table 1, p. 35, “Esophageal cancer”, references [65, 71-76] pre-date the priority claim of 27 November 2017).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the combination to include wherein the cancer-associated microorganism is S. pyogenes, Klebsiella pneumoniae, Lactobacillus acidophilus, or any combination thereof, by performing routine experimentation or optimization to select a specific strain of bacteria given its specific association with a specific cancer (Meng: Table 1, p. 35, “Esophageal cancer”), and for the benefit of enabling non-invasive, painless, and sensitive diagnosis of many cancers such as lung, breast, and gastric cancers (Buszewski: p. 89, col. 1, para. 2) and placing patients on a path for treatment (Buszewski: p. 93, col. 2, para. 2).
Response to Arguments
Applicant's arguments filed 12/01/2025 have been fully considered but they are not persuasive.
Claim Rejections under 35 U.S.C. § 101 – Subject Matter Eligibility
Applicant’s arguments dated 12/01/2025, have been fully considered but are not persuasive.
Applicant argues for Step 2A, Prong 1 that there is no abstract idea. The examiner disagrees. With respect to this, applicant argues that, “in the claimed method of treating cancer with chemotherapy, the cancer cells inability to survive chemotherapy is not considered to be a law of nature.” With respect to this--- the examiner points out that nothing about “cancer cells inability to survive chemotherapy,” is claimed, so this argument is not commensurate in scope with the instant claims. Further—even it this were claimed, this does not negate the fact that judicial exceptions are in fact claimed, as shown in the above rejection. The claimed treatment, is evaluated at Step 2A, 2 and 2 B to see if it practically applies or adds significantly more to the claimed judicial exceptions. It Is not evaluated at the 2A, Prong 1.
Applicant argues that at Step 2A, Prong two the claim as a whole integrates the exception into a practical application. Applicant argues that this is the case since the claims are an “improvement that integrate an abstract idea into a practical application.” The examiner disagrees. Applicant further argues that the treatments in Claim 1, step iv) are particular or specific. The examiner disagrees for the reasons shown above in the 101 rejection.
Applicant continues to argues that in step of (iv) of Claim 1, that each of the claimed treatments is specific and particular (so a practical application) to a specific stage of disease. With respect to this the examiner disagrees--- the examiner maintains that the claimed treatments are still not particular and specific, but include very general non named treatments like “a therapeutic agent capable of treating the cancer.” See the analysis provided in the above 101 rejection.
At Step 2B, applicant further argues that the claims amount to “improvement amounting to significantly more than a judicial exception.” The examiner disagrees for the reasons detailed in the 101 rejection above. Applicant argues that the claimed differential treatment for differently diagnosed stages of oesophago-gastric cancer makes this so. The examiner disagrees, since applicant has not made it clear how a differential diagnosis is done if one is actually done. As claimed, it seems like it just magically happens. Further--- the claimed treatments are not all particular or specific and include things like “a therapeutic agent capable of treating the oesophago-gastric cancer.” It is noted that only one of the claimed treatments need satisfied to fulfill the claim limitations. Further, all of the claimed types of treatments in all of step iv) steps a)-c) are well understood, routine and conventional in the art and therefore are not significantly more than the claimed judicial exceptions.
Applicant further argues that claim 1 has been amended to recite a specific “composition comprising the substrates of glucose, tyrosine, glutamic acid, and glycerol,” and that this/these substrates are “metabolized by a cancer associated bacterium into a signature compound,” and that this is not extra-solution activity, data gathering, or incidental to the primary process. The examiner disagrees. Again, since this supplement/composition is something that is ingested by a human ( like a food product), and then the blood sample is analyzed. Therefore, its extra -solution activity. Further- compositions like this are well understood and routine and conventional in the art to ingest, therefore this does not add significantly more.
Applicant again argues that the claims amount to “improvement amounting to significantly more than a judicial exception.” The examiner disagrees for the reasons detailed in the 101 rejection above. Applicant argues that the claimed differential treatment for differently diagnosed stages of oesophago-gastric cancer makes this so. The examiner disagrees, since applicant has not made it clear how a differential diagnosis is done if one is actually done. As claimed, it seems like it just magically happens. Further--- the claimed treatments are not all particular or specific and include things like “a therapeutic agent capable of treating the cancer.” It is noted that only one of the claimed treatments need satisfied to fulfill the claim limitations. Further, all of the claimed types of treatments in all of step iv) steps a)-c) are well understood, routine and conventional in the art and therefore are not significantly more than the claimed judicial exceptions.
Applicant further argues that the “specification as filed has described advantages of the claimed methods by stating that “analyzing the concentration of the signature compound in a bodily sample from a test subject and comparing this concentration with a reference for the concentration of the signature compound in an individual who does not suffer from cancer, wherein an increase or decrease in the concentration of the signature compound in the bodily sample from the test subject compared to the reference suggest that the subject is suffering from cancer, or has a pre-disposition thereto, or has a negative prognosis,” and advantageously the benefits for patients with cancer are earlier or immediate detection and avoiding watch-and wait analysis. Again, with respect to this, it is not clear if any differential diagnosis is actually done--- how it is performed instantly. It seems like it just magically happens based on the comparison of a measured level versus a reference level of signature compound. Further—the examiner notes, that much of the above argument is not in the instant claims, so this is not commensurate in scope with the claims. Therefore--- applicant’s argument that the instant claims are an improvement, and that they do not recite a judicial exception are not convincing.
The 101 rejection is maintained.
Claim Rejections under 35 U.S.C. § 112(b) – Indefiniteness
Some of the prior 112 b rejections are overcome due to amendments made 12/01/2025 however some are maintained as shown above, since the prior issues commented on were not fixed. Further 112 rejections are made due to the subject matter amended 12/01/2025.
Claim Rejections under 35 U.S.C. § 103
Applicant’s arguments with respect to claim(s) with respect to the prior art not teaching of administration of compound which has glucose, tyrosine, glutamic acid, and glycerol in it, it has 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.
Since the subject matter requiring the composition to contain all of tyrosine, glucose, glutamic acid, and glycerol was newly amended on 12/01/2025, a new piece of prior art, JP 4698843 was used to teach of this. JP 4698843 teaches of methods of detecting a monitoring uptake of bioactive agents by cells (title and abstract). JP 4698843 further teaches providing compositions for increasing cellular uptake of bioactive agents (paragraphs 0005). JP 4698843 further teaches that the composition can include glucose and glycerol (paragraph 0006), tyrosine, glutamic acid, and glutamine (paragraph 0009, 0049, 0053).
Applicant does not make any other substantive arguments about the prior art.
All claims remain rejected.
Conclusion
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758