DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed October 9, 2025. Currently, claims 1, 5-7, 9-11 are pending. Claims 1, 5-7 have been withdrawn as drawn to non-elected subject matter.
Election/Restrictions
Applicant's election without traverse of Group II, Claims 9-11 and Helicobacter in the paper filed October 9, 2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application claims foreign priority to CHINA 202111575146.5, filed December 22, 2021.
It is noted that a translation of the foreign document has not been received.
Drawings
The drawings are acceptable.
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 9-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena 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); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claim 9 is directed to “a method for determination or auxiliary determination of whether a sample is exposed to proton radiation” by extracting total DNA, performing PCR reaction, sequencing and data analysis and “determining whether the sample is exposed to proton radiation”. Claim 10 further requires that the abundance or relative abundance is greater than that of normal microbiota DNA.
The claims are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “data analysis”, “determining whether the sample is exposed to proton radiation” and a comparing step in Claim 10 for determining the abundance is greater than normal) and a law of nature/natural phenomenon (i.e. the natural correlation between the abundance of microbiota DNA in a subject and proton radiation exposure).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, the claims involve the patent-ineligible concept of an abstract process. Claim 9 requires performing the step of “determining whether the sample is exposed to proton radiation”. Neither the specification nor the claims set forth a limiting definition for "determining" and the claims do not set forth how “determining” is accomplished. As broadly recited the determining step may be accomplished mentally by thinking about a subject’s relative abundance of DNA and assessing whether the subject has been exposed to proton radiation. Thus, the determining step constitutes an abstract process idea.
The claim also generally states performing data analysis. The data analysis is a mathematical concept and a mental process. The data analysis encompasses an arithmetic calculation to generate a relative abundance value which may be practically performed in the human mind.
Claim 10 further recites a comparison between the abundance and a normal microbiome that is deemed an abstract idea (see MPEP 2106.04(a)(2)(III)(A); • claims to “comparing BRCA sequences and determining the existence of alterations,” where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014)).
A correlation that preexists in the human is an unpatentable phenomenon. The association between the abundance of microbiota DNA in a subject and proton radiation exposure is a law of nature/natural phenomenon. The "determining" step which tells users of the process to predict proton radiation exposure, amounts to no more than an "instruction to apply the natural law". This step is no more than a mental step. Even if the step requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The "determining" step does not require the process user to do anything in light of the correlation. The "determining" step fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.”
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites extracting total DNA, peforming PCR and sequencing, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The extracting total DNA, PCR amplification and sequencing amplicons are mere data gathering steps that amount to extra solution activity to the judicial exception. It merely tells the users of the method to sequencing total DNA of elected Helicobacter without further specification as to how the sample should be analyzed. The claims do not recite a new, innovative method for such determination. These essentially tells users to determine the markers through whatever known processes they wish to use.
The step of subjecting a resulting PCR amplification product to sequencing was well known in the art at the time the invention was made. The prior art teaches PCR amplification of Helicobacter and sequencing. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any PCR assay to sequence. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Additionally, the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements were well known.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112- Second Paragraph
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.
Claims 9-11 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 pre-AIA the applicant regards as the invention.
A) Claims 9-11 recite a method for auxiliary determination of whether a sample is exposed to proton radiation. It is unclear what auxiliary determination encompasses. Auxiliary is providing supplementary or additional help and support. It is unclear how this additional help or support is accomplished and how it is related to determining whether the sample is exposed to proton radiation. The specification does not provide any discussion of what auxiliary determination comprises. Thus, the metes and bounds of the claimed invention are unclear.
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.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim(s) 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. (Frontiers in Microbiology, Vol. 13, Article 874702, May 2022).
It is noted that the authorship of the Li et al. reference is distinct from the inventorship of the instant application and that this rejection may be overcome by the filing of a 132 Katz-type declaration or a declaration under 37 CFR 1.130(a) (see MPEP 717.01(a)(1)(B) “Where the authorship of the prior art disclosure includes the inventor or a joint inventor named in the application, an "unequivocal" statement from the inventor or a joint inventor that he/she (or some specific combination of named joint inventors) invented the subject matter of the disclosure, accompanied by a reasonable explanation of the presence of additional authors, may be acceptable in the absence of evidence to the contrary.”)
It is noted that a translation of the foreign document has not been received, therefore, the foreign priority cannot be relied upon to overcome the instant rejection.
Li teaches differences in the establishment of gut microbiota and metabolome characteristics between two mice after proton irradiation. Li teaches extracting DNA from fecal samples for microbiome analysis (page 13, col. 1). The extracted DNA was amplified and sequenced (page 13, col. 1). Li teaches analysis of Helicobacter (see Supplemental Figure 3). Thus, Li teaches each limitation of the instant claims.
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.
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 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Toxicological Sciences, Vol. 171, No. 1, pages 258-268, 2019) in view of Maier et al. (Carcinogenesis, Vol. 41, No. 4, pages 483-489, 2020).
Liu teaches impact of radiation on the composition of the gut microbiota of mice. Liu teaches feces from mice exposed to low-dose ionizing radiation. Liu teaches bacterial DNA was extracted from the fecal samples and quantified. Liu teaches PCR amplification followed by sequencing. Liu teaches analysis of elected Helicobacter as a gut microbiome element.
Liu does not teach analysis of proton radiation.
However, Maier teaches intestinal bacterial indicator phylotypes. Maier teaches Helicobacter rodentium was found in colons in the radiation-resistant CM-phenotype (abstract). In particular Maier teaches exposing mice to protons (H) at 2.0 GeV/n (page 484, col. 2). Maier teaches isolating RNA from blood and performing quantitative RT-PCR. Maier teaches Helicobacter was strongly associated with the radiation-resistant phenotype exhibited by the CM mice (page 485, col. 1). Maier teaches studies analyzed intestinal radiation tolerance in high-fractionated proton radiotherapy (page 484, col. 1). Maier teaches high-LET radiation was employed to explore the effects of irradiation (IR) induced intestinal microbiota changes.
Therefore, it would have been prima facie obvious at the time the invention was made to have analyzed DNA from a subject for Helicobacter using PCR and sequencing to analyze the quantity of microbiota DNA, as taught by Liu, to explore the effect of proton irradiation on microbiota changes, as taught by Maier.
Conclusion
No claims allowable over the art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Casero et al. (Microbiome, Vol. 5, No. 105, 2017) teaches space-type radiation induces multimodal responses in the mouse gut microbiome and metabolome. Casero does not teach analysis of elected Helicobacter in the sample.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
December 19, 2025