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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8 June 2026 has been entered.
Status
Any rejection not restated from the previous action is not maintained.
Claims 1, 4, 6, 7, and 11-16 are cancelled.
Claims 17-20 are withdrawn.
Claims 28-36 are newly added.
Claims 2, 3, 5, 8-10, and 21-36 are under examination.
Claim Rejections - 35 USC § 112 - Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 2, 3, 5, 8-10, and 21-36 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims are broadly drawn to methods for detecting or early diagnosing myocardial infarction (MI), predicting prognosis of MI and/or treatment outcome of MI in a subject (claims 21 and 26) and performing genetic analysis on gut microbiota (claim 27). All the claims include the step of determining if there is an increased abundance of gut microbial genera when compared to a control without MI.
Factors to be considered
In determining whether a disclosure meets the enablement requirement of 35 USC § 112, first paragraph, factors have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988).
Wands states on page 1404,
"Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skills of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims."
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make or use the claimed invention, if not, whether an artisan would require undue experimentation to make and use the claimed invention and whether working examples have been provided.
The Nature of the Invention
The nature of the presently claimed invention is determining abundance of microbial genera Streptococcus, Clostridium, and /or Butyricimonas in a sample from a subject and determining if there is an increase in those genera compared to a control without MI. Such an invention has potential use in the art for diagnosing myocardial infarction, however, the nature of such an invention is within the broad genera of using a biological sample to make a diagnostic determination, and, as shown below, Applicants' invention, as claimed, is not enabled due to problems with the complexity, unpredictability, and unknown correlation between levels of the microbial genera as an indicator in the biological sample, lack of specific guidance, state of the art, and the amount of experimentation required to successfully practice the claimed invention.
The Breadth of the Claims
The instant claims are drawn to the use of a biological sample to determine a level of microbial genera in the biological sample and diagnose or determine if the subject has a myocardial infarction, will have a myocardial infarction, or their prognosis or treatment prognosis. The aspects considered broad is the correlation between the microbial genera abundance and the diagnosis. As will be shown below, this aspect is not enabled. It is noted that claims compare the abundance to a control without MI and the preamble states the intended use.
Predictability and State of the Art
The art is unpredictable. With respect to diagnosis of MI by detecting abundance of microbial genera, the art does not show any correlation with the microbial genera and if they will have a myocardial infarction.
There is nothing in the specification to indicate any species of Streptococcus, Clostridium, or Butyricimonas can be used to diagnose MI. The specification indicates that samples were collected from patients within three days of STEMI intervention and 28 days later in the examples. There is nothing in the specification to indicate samples were taken before patients had a STEMI.
Regarding the colonization step in claim 21, the specification is limited to mice studies that treat the mice with an antibiotic to deplete their gut microbiota and then the gut is colonized with specific microbial species.
The prior art does not show any correlation between diagnosis of MI and microbial genera. Kim (EP 3 567 118 B1) indicate that Streptococcus species are lower than a control in patients already diagnosed with STEMI. Kim does not teach testing subjects before STEMI.
Hence, from the nature of the invention and the state of the art, the Artisan would not reasonably predict that determining the abundance of microbial genera would be predictive of myocardial infarction or prognosis or treatment outcome.
The Amount of Direction or Guidance/The Existence of Working Examples
The specification does not provide any guidance regarding diagnosing or determining if a subject will have MI or predicting prognosis or treatment outcome.
The specification provides cites to studies that detected abundance of the microbial genera in patients that already experienced a STEMI event.
Amount of Experimentation Necessary
There would be a large and prohibitive amount of experimentation required to make and use the claimed invention in the full scope as encompassed by the claims. One would have to perform a large scale study detecting abundance of microbial genera in patients that do not have myocardial infarction and track them to see if they have an MI event. The fact that STEMI patients in a study showed a difference in microbial genera abundance is not determinative of a diagnosis.
Conclusion
In conclusion, the instant specification is not enabling because one cannot follow the guidance presented therein and practice the claimed methods without first making a substantial inventive contribution. As such, claims 2, 3, 5, 8-10, and 21-36 are not enabled, because there would be an undue amount of experimentation required to make and use the invention as claimed.
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 2, 3, 5, 8-10, 21-26, and 28-36 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.
Claim 21 recites a method for detecting or early diagnosing myocardial infarction (MI), predicting prognosis of MI and/or treatment outcome of MI in subject. Claim 26 does not recite any active method step for achieving the intended method in the preamble. The claim recites the steps of obtaining a sample, performing a genetic analysis on the gut microbiota from the sample, determining if an increased abundance of gut microbial populations are found compared to a control without MI and colonizing the gut of the subject with bacterial strains if the abundance is increased compared to a control without MI. (the examiner has paraphrased the steps). None of those steps recite detecting or early diagnosing MI, predicts the prognosis of MI, nor predicts the prognosis of a treatment outcome of MI. It is not clear from the claim if the intended use is achieved.
Claims 2, 3, 5, 8-10, and 22-25 depend from claim 21 and do not overcome the rejection because they do not add any additional active method steps that relate to the preamble.
Claim 26 recites a method for detecting or early diagnosing myocardial infarction (MI), predicting prognosis of MI and/or treatment outcome of MI in subject. Claim 26 does not recite any active method step for achieving the intended method in the preamble. The claim recites the steps of obtaining a sample, performing a genetic analysis on the gut microbiota from the sample, and determining if an increased abundance of gut microbial populations are found compared to a control without MI. (the examiner has paraphrased the steps). None of those steps recite detecting or early diagnosing MI, predicts the prognosis of MI, nor predicts the prognosis of a treatment outcome of MI. It is not clear from the claim if the intended use is achieved.
Claims 28-36 depend from claim 26 and do not overcome the rejection as they do not add any additional steps that relate to the preamble.
Claim 21 is indefinite because it is not clear from the claims what is achieved with the colonization step. The performing step is detecting Streptococcus, Clostridium, and/or Butyricimonas and if they are increased compared to the control, the subject gut is colonized with more Butyricimonas or Streptococcus. That step would increase an already elevated level of that genus in the gut.
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 2, 3, 5, 8-10, and 21-36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a natural phenomenon and an abstract idea) without significantly more. The claim(s) recite(s) detecting or early diagnosing myocardial infarction (MI), predicting prognosis of MI and/or treatment outcome of MI in subject and claim 27 recites performing a genetic analysis on gut microbiota. These judicial exceptions are not integrated into a practical application based on the reasoning below:
The unpatentability of laws of nature and abstract ideas was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Diamond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S., (2010) (slip op., at 5). “Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U. S. 63, 67 (1972).
Additionally, the unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010) and in Alice Corp. v. CLS Bank Inti, 134 S. Ct. 2347, 2354 (2014).
The following inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim to a process, machine, manufacture, or composition of matter? Yes, the claims are directed to methods.
Step 2A, prong 1. Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)? Yes. Regarding independent claims 21 and 26, where the claims recite detecting or early diagnosing myocardial infarction (MI), predicting prognosis of MI and/or treatment outcome of MI in subject they encompass the mental comparison of data and the correlation of data and information to reach a conclusion. Further, the diagnosis is based on a law of nature or natural phenomenon because it is based on levels of gut microbiota already occurring in the subject. Both claims 21 and 26 recite “compared to a control without MI.” And while they do not recite a final diagnosis step as detailed above under 35 USC 112, they do make a comparison.
Regarding claim 27, where the claim recites determining if there is an increased abundance of microbial populations compared to a control without MI, they encompass the mental comparison of data and the correlation of data.
Step 2A, prong 2. Does the claim recite additional elements that integrate the exception into a practical application? No, the judicial exceptions to which the claims are directed are not integrated into a practical application because the rejected claims do not require any particular practical steps related to the determining a biomarker level and predicting response to a treatment. Claims 26 and 27 recite using a computer executable program, however reciting a generic computer does not overcome an eligibility rejection. The claims do not recite anything other than a computer executable program.
Step 2B. Does the claim recite additional elements that amount to significantly more than the judicial exception? No, the claims only recite diagnosis or determining myocardial infarction. Claim 21 recites colonizing the gut of the patient if the abundance if increased to a control and therefore is a conditional limitation based on the abundance levels.
For these reasons, the claims are rejected under USC 35 section 101 as being directed to non-statutory subject matter.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
O’Morain and Ramji, The Potential of Probiotics in the Prevention and Treatment of Atherosclerosis (2020).
Lau et al., Bridging the Gap between Gut Microbial Dysbiosis and Cardiovascular Diseases (2017).
Lewis and Taylor, Intestinal barrier dysfunction as a therapeutic target for cardiovascular disease (2020).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MINDY G BROWN whose telephone number is (571)270-5605. The examiner can normally be reached Monday -Friday, 9:00 am - 5:00 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MINDY G BROWN/Patent Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
