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 .
The amendments and responses filed on December 30, 2026, and May 20, 2026, are received.
Claims 8, 12, 17-18 and 24 are canceled by Applicant.
Claims 1-7, 9-11, 13-16 and 19-23 are pending in this application, claims 9-11 and 14-16 are withdrawn from further consideration (See Restriction/Election below), and claims 1-7, 13 and 19-23 are being examined to the extent they read on elected species.
Restriction/Election:
Applicant’s election of Group I, claims 1-7, 13 and 19-23, in the reply filed on 12/30/2025 is acknowledged, and the election of the species of metabolic biomarkers “assessing the level of deoxycholic acid, isodeoxycholic acid, lithocholic acid, and desaminotyrosine” in the reply filed on 05/20/2026 is also acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim 24 (drawn to the non-elected invention) is canceled by the Applicant in the reply filed on 05/20/2026.
Claims 9-11 and 14-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/20/2026.
Objection(s):
Claim(s):
Claims 19, 21 and 22 are objected to because of the following informalities:
In claim 19, line 3 (end of the line), replace “desaminotyrosine” with –-desaminotyrosine--.
In claim 21, line 3 (end of the line), replace “desaminotyrosine” with –-desaminotyrosine--.
In claim 19, line 3, replace “desaminotyrosine” with –-desaminotyrosine--.
Appropriate correction is required.
Specification:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (See for example, pages 36 and 39). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 1-7, 13 and 19-23 are rejected under 35 U.S.C. 101 because:
The claimed invention is directed to a judicial exception, i.e., as abstract idea, without significantly more.
According to Section I of the 2019 Revised Patent Subject Matter Eligibility Guidance, “the judicial exceptions are for subject matter that has been identified as the ‘‘basic tools of scientific and technological work,’’ which includes ‘‘abstract ideas’’ such as mathematical concepts, certain methods of organizing human activity, and mental processes; as well as laws of nature and natural phenomena”, and “the USPTO has set forth a revised procedure, rooted in Supreme Court caselaw, to determine whether a claim is ‘‘directed to’’ a judicial exception under the first step of the Alice/Mayo test (USPTO Step 2A).” (Also see “2019 Revised Patent Subject Matter Eligibility Guidance, Federal Register / Vol. 84, No. 4 / Monday, January 7, 2019 / Notices, p. 50-57”).
Therefore, if the claim does recite a judicial exception (a law of nature, natural phenomenon, or subject matter within the enumerated groupings of abstract ideas in Section I), then the claim is NOT eligible at Prong One of revised Step 2A.
Claim 1 reads:
1. A method of assessing the level of one or more biomarkers of mortality in the gut of the subject comprising assessing a level of one or more metabolomic biomarkers in the fecal sample from the subject (the elected species).
And further claims 2-7, 13 and 19-23 read:
2. The method of claim 1, wherein the subject suffers from respiratory insufficiency.
3. The method of claim 2, wherein the subject suffers from severe respiratory insufficiency.
4. The method of claim 1, wherein the subject suffers from COVID-19.
5. The method of claim 4, wherein the subject suffers from COVID-19 acute respiratory distress syndrome (ARDS).
6. The method of claim 1, wherein the subject is hospitalized.
7. The method of claim 6, wherein the subject is ventilated.
13. The method of claim 1, wherein the level of one or more metabolomic biomarkers is assessed by mass spectrometric analysis of a sample from the subject.
19. The method of claim 1, wherein the level of two or more of deoxycholic acid, isodeoxycholic acid, lithocholic acid, and desaminotyrosine are assessed, wherein high levels of the two or more of deoxycholic acid, isodeoxycholic acid, lithocholic acid, and desaminotyrosine is associated with a high risk of mortality.
20. The method of claim 19, wherein high levels are levels above a threshold value.
21. The method of claim 20, wherein the threshold is between 70 µM and 110 µM for deoxycholic acid, between 0.8 µM and 1.2 µM for isodeoxycholic acid, between 220 µM and 300 µM for lithocholic acid, and between 10 µM and 30 µM for desaminotyrosine.
22. The method of claim 21, wherein the threshold is about 90 µM for deoxycholic acid, about 1 µM for isodeoxycholic acid, about 258 µM for lithocholic acid, and about 21 µM for desaminotyrosine.
23. (original) The method of claim 19, comprising assessing the levels of each of deoxycholic acid, isodeoxycholic acid, lithocholic acid, and desaminotyrosine.
In this case, the recited step“ assessing a level of one or more metabolomic biomarkers in the fecal sample from the subject (the elected species)”, under the broadest reasonable interpretation, covers mental processes, for example, performing the assessment in human mind (analyzing and interpreting data, etc.).
In addition, there are no additional element(s) recited in claims 1-7, 13, and 19-23 that precludes the step from practically being performed in the mind.
According to the above-mentioned Guidance in Prong Two, examiners evaluate whether the claim recites additional elements that integrate the exception into a practical application of that exception. This prong adds a more detailed eligibility analysis to step one of the Alice/Mayo test (USPTO Step 2A) than was required under prior guidance.
Because there are not any additional elements recited in the claim beyond the judicial exception, the claimed method as recited in claims 1-7, 13, and 19-23, do not integrate the judicial exception into a practical application, because they do not impose any meaningful limits on practicing the abstract idea. The claims are directed to an abstract idea.
Therefore, the claimed method is not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-7, 13 and 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kakiyama et al. (2013, Volume 58, Issue 5, p. 949-955) as evidenced by Then et al. (S1056, Cirrhosis and Acute Respiratory Distress Syndrome (ARDS) Examining the Link: A Nationwide Retrospective Study. The American Journal of Gastroenterology 115():p S536, October 2020, 1 page).
Regarding claim 1, Kakiyama et al. disclose a method of assessing the level of one or more biomarkers of mortality in the gut of the subject comprising: (a) assessing a level of one or more bacterial species in a fecal sample from the subject; and/or (b) assessing a level of one or more metabolomic biomarkers in the fecal sample from the subject (the elected species) (analysis of fecal bile acids from subject subjects having advanced cirrhosis) (See for example, p. 950 right-hand column last paragraph and p. 951 Table 2 and related description), bile acids especially CA and DCA, can modulate the population of colonic bacteria … this in turn potentiate complications related to deficient gut barrier function which are pre-mortal events in advanced cirrhosis) (See for example, p. 954 left-hand column 3rd paragraph).
Regarding claims 2-7, it should be noted that before the effective filing date of the invention, Then et al. disclose the subjects disclosed by Kakiyama et al., suffers from respiratory insufficiency, severe respiratory insufficiency, COVID-19 acute respiratory distress syndrome or ARDS, the subject is hospitalized and the subject is ventilated (90% mortality rate patients with cirrhosis, and overlap due to the presence of cirrhosis in patients with respiratory insufficiency, severe respiratory insufficiency, ARDS in the setting of coronavirus) (See for example, ”Introduction”, “Methods” “Results” and “Conclusion”).
Regarding claim 13, Kakiyama et al. disclose the level of one or more metabolomic biomarkers is assessed by mass spectrometric analysis of a sample from the subject (tandem mass spectrometry) (See for example, p. 950 left-hand column title “Bile acid analysis”).
Regarding claims 19 and 20, Kakiyama et al. disclose the level of two or more of deoxycholic acid, isodeoxycholic acid, lithocholic acid, and desaminotyrosine are assessed, wherein high levels of the two or more of deoxycholic acid, isodeoxycholic acid, lithocholic acid, and desaminotyrosine is associated with a high risk of mortality subject (decreased conversion of primary to secondary fecal bile acids (BAs), including deoxycholic acid or DCA and lithocholic acid or LCA compared to controls which worsen the severity of the liver disease, … bile acids especially CA and DCA, can modulate the population of colonic bacteria … this in turn potentiate complications related to deficient gut barrier function which are pre-mortal events in advanced cirrhosis) (See for example, p. 950 right-hand column title “statistical analysis”, p. 954 right-hand column 2nd paragraph, and p. 954 left-hand column 3rd paragraph).
Kakiyama et al. therefore anticipate the claimed method of assessing the level of one or more biomarkers of mortality in the gut of the subject.
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 nonobviousness.
Claims 1-7, 13 and 19-22 are rejected under 35 U.S.C. 103 as being unpatentable over Kakiyama et al. (2013, Volume 58, Issue 5, p. 949-955) as evidenced by Then et al. (S1056, Cirrhosis and Acute Respiratory Distress Syndrome (ARDS) Examining the Link: A Nationwide Retrospective Study. The American Journal of Gastroenterology 115():p S536, October 2020, 1 page).
Regarding claim 1, Kakiyama et al. teach a method of assessing the level of one or more biomarkers of mortality in the gut of the subject comprising: (a) assessing a level of one or more bacterial species in a fecal sample from the subject; and/or (b) assessing a level of one or more metabolomic biomarkers in the fecal sample from the subject (the elected species) (analysis of fecal bile acids from subject subjects having advanced cirrhosis) (See for example, p. 950 right-hand column last paragraph and p. 951 Table 2 and related description), bile acids especially CA and DCA, can modulate the population of colonic bacteria … this in turn potentiate complications related to deficient gut barrier function which are pre-mortal events in advanced cirrhosis) (See for example, p. 954 left-hand column 3rd paragraph).
Regarding claims 2-7, it should be noted that before the effective filing date of the invention, Then et al. teach the subjects taught by Kakiyama et al., suffers from respiratory insufficiency, severe respiratory insufficiency, COVID-19 acute respiratory distress syndrome or ARDS, the subject is hospitalized and the subject is ventilated (90% mortality rate patients with cirrhosis, and overlap due to the presence of cirrhosis in patients with respiratory insufficiency, severe respiratory insufficiency, ARDS in the setting of coronavirus) (See for example, ”Introduction”, “Methods” “Results” and “Conclusion”).
Regarding claim 13, Kakiyama et al. teach the level of one or more metabolomic biomarkers is assessed by mass spectrometric analysis of a sample from the subject (tandem mass spectrometry) (See for example, p. 950 left-hand column title “Bile acid analysis”).
Regarding claims 19 and 20, Kakiyama et al. teach the level of two or more of deoxycholic acid, isodeoxycholic acid, lithocholic acid, and desaminotyrosine are assessed, wherein high levels of the two or more of deoxycholic acid, isodeoxycholic acid, lithocholic acid, and desaminotyrosine is associated with a high risk of mortality subject (decreased conversion of primary to secondary fecal bile acids (BAs), including deoxycholic acid or DCA and lithocholic acid or LCA compared to controls which worsen the severity of the liver disease, … bile acids especially CA and DCA, can modulate the population of colonic bacteria … this in turn potentiate complications related to deficient gut barrier function which are pre-mortal events in advanced cirrhosis) (See for example, p. 950 right-hand column title “statistical analysis”, p. 954 right-hand column 2nd paragraph, and p. 954 left-hand column 3rd paragraph).
Moreover, regarding claims 21 and 22, the claimed thresholds (µM) for the markers, deoxycholic acid and lithocholic acid, in the method taught by Kakiyama et al. would have been optimized by a person of ordinary skill in the art before the effective filing dated of the invention by routine experimentation.
Conclusion(s):
No claim(s) is allowed at this time.
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/KADE ARIANI/Primary Examiner, Art Unit 1651
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