DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
2. The information disclosure statement (IDS) submitted on 01/27/23 was filed and entered. The submission is in compliance with the provisions of 37 CFR 1.97 and has been considered by the Examiner.
Claim Status
3. The amendment, filed 01/27/23, has been entered. Claims 1-17 are cancelled. Claims 18-36 are newly added, pending, and under examination.
Claim Rejections - 35 USC § 101
4. 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.
5. Claims 18-36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (e.g. abstract ideas: mathematical concepts and mental processes) without significantly more.
Independent claim 18 recites, in part, “A method for establishing a microbiome niche map comprising …(c) determining an absolute or relative abundance of individual microbe population in the first microbiome test sample at the end of step (b) …(e) determining an absolute or relative abundance of individual microbe population in the second microbiome test sample at the end of step (d), (f) determining microbe population differentially enriched between the first and the second test sample by subtracting the absolute or relative abundance of an individual microbe population of step (c) from the absolute or relative abundance of the same individual microbe population of step (e), … and (h) attributing the enriched microbe population of step (f) or (g) to a specific niche condition” which amounts to mental processes such as concepts performed in the human mind including observation, evaluation, judgement, and/or opinion (e.g. limitations encompass just looking at growth in test samples and evaluating relatively “more” vs. “less”) and mathematical concepts (i.e. determining differentially enriched via subtraction; i.e., which one has “more”).
Similarly, with regards to claim 34, “A method for identifying a pattern of enriched individual microbe populations associated with a condition … comprising performing the method of claim 18 … and identifying said condition”; and claim 35, “A method for developing a probiotic composition… comprising … determining the niche map … according to claim 18…and developing a composition”; and claim 36, “A method for predicting the response of a subject to a treatment… comprising … determining the niche map … according to claim 18… comparing the microbiome niche map of the subject to a microbiome niche map of a reference… and determining under-representation and/or over-representation of niches… being indicative of the response…” these preambles and limitations also amount to mental processes and mathematical concepts (i.e. identifying, developing, predicting, and/or comparing).
Therefore, although the claims are drawn to a statutory category, i.e., methods; and thus, Step 1 of the subject matter eligibly analysis is yes; the claims also recite judicial exception(s), e.g., mathematical concepts and mental processes; and accordingly, Step 2A, prong 1, is also yes.
These judicial exceptions are not integrated into a practical application because the positively recited steps in claim 18 of “…(a) providing a microbiome sample distributed into at least two microbiome test samples, (b) growing a first microbiome test sample of step (a) in a reference niche condition … (d) growing a second microbiome test sample of step (a) in a niche condition that differs in at least one parameter from the reference niche condition…” amount to pre-solution data gathering steps required to subsequently execute the mental processes and mathematical concepts. Dependent claims either add additional pre-solution data gathering steps (e.g. see claims 23 and 24) or specify how and/or what will be analyzed (e.g. claims 19-22 and 25-33), but there are no other required steps in claims 18-33 once the mental processes and mathematical calculations are made. Therefore, nothing is done with the information gathered and, accordingly, the judicial exception is not integrated into a practical application. For claims 34, 35, and 36, although the method of claim 18 appears to be used for another purpose, those purposes (i.e. identifying a pattern, developing a composition, and predicting a response) are each a judicial exception themselves (i.e. mental processes). For example, even in claim 35, a composition per se is not actually made, it is only required to be “developed” which could easily be done by thinking about (i.e. abstract idea) the observations made during the method of claim 18. However, in the interest of completeness, it is noted that merely adding the words “apply it” (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer, or merely uses a computer as a tool to perform an abstract idea does not integrate an abstract idea into a practical application. Therefore, Step 2A, prong 2, is no.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions because there are no other elements since all other claim limitations encompass details of the pre-solution data gathering steps (i.e. add additional pre-solution data gathering steps, see claims 23 and 24; or specify how and/or what will be analyzed, see claims 19-22 and 25-33), needed to subsequently conduct the mental processes and/or mathematical calculations. Similarly, claims 34-36, introduce additional judicial exceptions (abstract ideas). Thus, taken alone, the additional elements do not amount to significantly more than the above identified judicial exceptions (i.e. abstract ideas: mental processes of observing, evaluating, and making judgments/opinions and mathematical calculations of determining abundances; subtracting values; comparing values; and/or assessing over- and under-representations). Looking at the limitations as an ordered combination adds nothing that is not already present when looking at the elements taken individually because there is nothing significant beyond the sum of their parts taken separately. It is also noted that simply appending well-understood, routine, conventional activities previously known to the scientific community, specified at a high level of generality, to the judicial exceptions would not be sufficient; see MPEP 2106.05(d).
Therefore, Step 2B is no and the claims are rejected as ineligible subject matter under 35 U.S.C. 101.
Claim Rejections - 35 USC § 112
6. 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.
7. Claims 18-36 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 18 is indefinite because the steps in the body of the claim do not meet the goal of the preamble. For example, the claim reads “A method for establishing a microbiome niche map…” however, the steps of the method, including providing a microbiome sample, growing sub-samples under different conditions, comparing the results obtained, and attributing differences in growth to the differences in conditions, does not establish a map, in general, or a microbiome niche map, in particular. Consequently, it is unclear how to meet the goal of the preamble. Further, claim 18 is indefinite because it is unclear what Applicant is attempting to encompass with the phrase “…individual microbe population…” For example, is it the individual microbe’s population (i.e. distinct numbers corresponding to each distinct microbial species?) or is it one (i.e. individual) microbe population (i.e. one total number of microbes?). Thus, clarification is required to remove scope ambiguity.
With regards to “relative abundance” in claims 18, 20, and 21 the term “relative” is a relative term (literally) which renders the claim indefinite. For example, to what is the abundance to be compared to in order to establish the relative amount (i.e. relative to what?). Thus, clarification is required to remove scope ambiguity.
Claim 21 further confounds the issue in claim 18 with regards to what “…individual microbe population…” encompasses. It is also unclear how the absolute abundance in claim 21 (see line 1) is determined using the total microbial growth (i.e. results) of only one of step (b) or (d) and not both (see line 3) and is then added (i.e. see “and (ii)…” to the relative abundance of only one of step (b) or (d) and not both (see line 4). In other words, in step (f) of claim 18, the growth results are required to be subtracted which requires subtractable values (i.e. both absolute or both relative), but claim 21 allows/requires a mix (i.e. one absolute and one relative) which does not make sense. Thus, clarification is required to remove scope ambiguity.
Similarly, claim 22 is internally inconsistent. For example, claim 22 part (i) allows determining either optical density or microbial DNA of either claim 18 step (b) or step (d), but not both; and then part (ii), which is required based on the “and” in line 3, then requires sequencing of the total microbial DNA from either (b) or (d), but not both (i.e. optical density data cannot be sequenced). Thus, once again, step (f) of claim 18 cannot be completed because it requires subtractable numbers, which claim 22 does not necessarily provide. Thus, clarification is required to remove scope ambiguity.
The term “suitable” in claim 23 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. In other words, how suitable and/or suitable for what? Thus, clarification is required.
Regarding claim 24, the phrase “in particular” is being interpreted as "for example" which renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention; see MPEP § 2173.05(d). In the interest of compact prosecution, the limitation is interpreted to not be limited to the four options, but rather, encompass all pre-treatment steps. Nevertheless, clarification is required to remove ambiguity of scope.
Claim 25 is unclear because it appears to be missing some (or using the wrong) words. For example, the first recitation of time (following the word “two”) should most likely be “times” (plural) and the phrase “… with each time a different niche condition or parameter” is unclear because the time per se is not the different condition or parameter (consider: “…with each time having a different…”). Regardless, clarification is required in order to understand the scope of this claim.
Claims 26 and 27 recites the limitation "the niche condition parameter" in line 1. There is insufficient antecedent basis for this limitation in either claim because there is no recitation of “a niche condition parameter” in claim 18, from which each directly depends (i.e. also see claim 25 which distinguishes niche conditions from parameter: “…a different niche condition OR parameter”). Thus, clarification is required to remove scope ambiguity.
The term “substrate” in claim 26 in the list of alternatives is unclear because “substrate” is not a niche condition or parameter (i.e. as opposed to a concentration of a substrate, or the presence or absence of a substrate). Thus, clarification is required to remove scope ambiguity.
Claims 27 and 30 are each unclear because each contains improper Markush-type language. The proper language for a list of alternatively useable species is either (a) wherein R is selected from the group consisting of A, B, C and D or (b) wherein R is A, B, C, or D; however these claims use a combination of both “and” and “or” or multiple “or”. Thus, clarification is required to ascertain the metes and bounds.
Claim 28 is indefinite because of the use of parentheses. Although parenthesis may be appropriate when defining an abbreviation or acronym (see line 7), the inclusion of parentheses for phrases (see lines 3, 4, and 5), raises uncertainty as to whether the feature in the parentheses is optional or always present. Thus, clarification is required to ascertain the metes and bounds of these claims. The Office suggests the use of commas or semicolons. Further, claim 28 lists inulin twice and includes items that are not actually substrates (e.g. surface glycosylation; see lines 10-11). Thus, clarification of the entire list is required to remove scope ambiguity.
The phrase “associated with” in claim 34 (see line 2) is a relative term which renders the claim indefinite. The phrase “associated with” 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. In other words, to what degree of association is required to be included (vs. excluded) in the scope of the claim? Also regarding claim 34, the phrase “for instance” (see line 4) is being interpreted as "for example" which renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention; See MPEP § 2173.05(d). Thus, clarification is required to remove scope ambiguity.
Claim 35 is indefinite based on the phrase “…susceptible to benefit to a patient” because the phrase does not make sense for a method of developing a probiotic composition found in the preamble. Thus, clarification is required to remove scope ambiguity.
Other dependent and/or linking claims do not clarify the issues identified above. Accordingly, clarification is required to remove scope ambiguity and ascertain the metes and bounds of these claims.
Claim Rejections - 35 USC § 102
8. 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 (i.e., changing from AIA to pre-AIA ) 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.
9. 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.
10. Claims 18-28 and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lennon et al. 2012 (Mapping the niche space of soil microorganisms using taxonomy and traits; Ecology 93(8):1867-1879).
Lennon teaches methods of mapping microbial niches of soil comprising extracting soil bacteria from 1 gram of soil (i.e. providing a microbiome sample; a soil microbiome) using 10 mL of 1% sodium pyrophosphate (i.e. a suitable dilution agent; also a pre-treatment step) and then plating on R2 agar (i.e. growing one test sample; non-selective growth media) or Pseudomonas isolation agar (i.e. growing a second test sample under different conditions; different niche condition being substrate and/or cultivation method; selective growth media containing gelatin and meat peptone, see Pertinent Art section below) and incubated at a range of temperatures (i.e. also a different niche condition: temperature) for up to one year (i.e. also a different niche condition: incubation time) to yield 23 strains of bacteria subsequently sequenced, mapped, and classified (e.g. page 1868, Methods section; and Figures 1 and 5; meeting limitations found in instant claims 18, 22, 24, 25, 26, 27, 28, and 30). Lennon teaches mapping niches of microorganisms along a soil moisture gradient (i.e. also a different niche condition: humidity) comprising manipulating the water potential within a set of microcosms (i.e. at least first and second test samples) and inoculating 100 mL of log phase microbial culture for determining and monitoring microbial respiration (i.e. a function of relative abundance and positively correlated to absolute abundances measured by qPCR and plate counts) multiple times along the moisture gradient (see page 1869, right column; and Figures 2, 3, 4 and 6; meeting limitations found in instant claims 18, 19, 20, and 21). Lennon teaches the ability to identify microbial functional groups based on taxonomy and traits provides a basis for making predictions about how microbial communities with respond, both compositionally and functionally, to changing conditions (e.g. page 1878, left column, conclusion).
Therefore, Lennon anticipates the invention as claimed.
Claim Rejections - 35 USC § 102
11. Claims 18-22, 24-28, and 30-35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lawley et al. 2017 (WO 2017/064263A1).
Lawley teaches methods for mapping microbiomes comprising obtaining a sample, including fecal and/or skin samples, comprising microorganisms from human individuals that are either healthy or have a disease or dysbiosis and analyzing a first portion using whole genome shotgun sequencing of DNA to obtain indications of the relative abundances of one or more lineages or reference genomes; and then obtaining a plurality of sequence reads from a second portion of the sample that has been cultured using a bacterial culturing method (i.e. different conditions from the first test sample; niche condition is presence of substrates, cultivation method, incubation time, and/or promoting growth factors) and comparing the indications of the relative abundances of the lineages and/or reference genomes within the first portion of the sample with the indications of the relative abundances of the lineages and/or reference genomes with the second portion to identify differences for the purpose of uniquely mapping those lineages in the microbiome (e.g. page 4, lines 23-34; page 12, lines 10-30; page 13, lines 1-30; page 14, lines 6-32; and Figure 11; meeting limitations found in instant claims 18, 20, 21, 22, 26, 30, 32, 33 and 34). For example, Lawley teaches culturing bacteria using the broad range medium YCFA (i.e., Yeast Casitone Fatty Acids; contains yeast extract, growth factors, peptides from the pancreatic digest of casein, amino acids, vitamins, and carbohydrates; see Pertinent Art section below), with and without prior ethanol treatment (i.e. a pre-treatment step), and with the addition of taurocholate (i.e. a bile acid), resulted in bacteria from 97% of most abundant genera and 90% of the most abundant species being detected in a sample and that it is expected that reiteration of the culturing step (i.e. repeating the process) using an alternate medium (i.e. change in culturing conditions to other niche conditions; niche condition: substrate) would allow an even higher proportion (e.g. percentage) of the bacterial genera and bacterial species present in a sample to be cultured (e.g. page 14, lines 35-43; meeting limitations found in instant claims 18, 19, 22, and 25-28). Lawley teaches both absolute (e.g. colony counting) and relative (i.e. percentages) abundances (e.g. page 40, lines 1-12; meeting limitations found in instant claims 18, 19, 20, and 21). Lawley provides an example of treatment of fecal samples with ethanol (i.e. see experiments with and without ethanol which is a niche substrate and an organic molecules of plant origin; see Example 3 and page 40, lines 29-44; and Figure 12; meeting limitations found in instant claims 18, 24, 26, 27, and 28). Lawley teaches the ethanol enriched the ethanol-resistant bacteria relative to the original profile of bacteria (i.e. identified a pattern of enriched individual microbe populations in a subject; see Example 3; meeting limitations found in instant claim 34). Lawley teaches multiple, alternate, bacterial culturing methods may be performed in parallel, using multiple portions of the same samples, or sequentially using different samples to determine bacteria present (e.g. page 14, lines 6-16; meeting limitations found in instant claims 25 and 31). Lawley describes examples of methods of the invention for identifying bacterial lineages present in the sample which have been cultured using a set of bacterial culture conditions, and then adjusting culture conditions as necessary to culture bacteria not cultured using an original set of bacterial culture conditions, obtaining whole genomic sequences and/or cultures of bacteria cultured using a suitable set of bacterial culture conditions (see Example 2; meeting limitations found in instant claim 34). Lawley teaches the methods may be used to identify bacteria that are useful in bacteriotherapy for subjects with a dysbiosis such as a Clostridium difficile infection (e.g. see Example 1; Figure 5; page 54 line 29 to page 55, line 8 and Lawley claims 24 and 25; meeting limitations found in instant claim 35).
Accordingly, Lawley anticipates the invention as claimed.
Claim Rejections - 35 USC § 102
12. Claims 18-36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Berry et al. 2016 (US 2016/0143961).
Berry teaches methods of mapping microbiomes comprising obtaining a sample, culturing the sample, extracting DNA from the sample, including samples from the skin, vagina, and/or gut, and 16S-sequencing the DNA to define taxonym assignments using sequence similarity and phylogenetic placement and comparing a sequence read (i.e. second test sample) to a reference read (i.e. a first test sample) from a reference database wherein the taxonomic and phylogenetic abundance data from various niches are then subjected to comparative analyses to identify microbes that are unique to each site and those that overlap between two of more sites (e.g. see [0188-0192; 0254-0255, 0691]; Examples 2-6, 19 and 32; meeting limitations found in instant claims 18, 22, 27, 29 and 30). Berry teaches the microbiome may be characterized in terms of absolute or relative abundances (e.g. [0150-0151]; meeting limitations found in instant claims 18, 19, 20, and 21). Berry teaches methods of making compositions wherein candidate microbes (i.e. developing a probiotic composition) to be used for mitigating disease (e.g. GVHD) conditions (i.e. response to treatment, including the impact of nutrition) are selected based on microbiome analysis of sample taken from a single or multiple niche(s) including those that are highly abundant (i.e. enriched; over-represented) in patients who do not succumb to GVHD (i.e. good-responders) are associated with low or no GVHD incidence and these microbes are then tested in vitro and in vivo models to test their ability to inhibit inappropriate immune responses and reduce inflammation at multiple disease target sites such as the gul, liver, kidney, lung and/or skin (e.g. see [0223-02240390, 0544-0547, 0551-0553]; Example 33; meeting limitations found in instant claim 18, 34, 35 and 36). Berry teaches methods for measuring the effect of microbes, with and without prebiotics, including polysaccharides on bacterial metabolites such as short-chain fatty acids because they are important modulators of the immune system (e.g. see Examples 48 and 51; meeting limitations found in instant claims 18, 26, 27, and 29). Berry teaches prebiotics include xylose and dextran (e.g. [0014]; meeting limitations found in instant claim 28). Berry teaches methods for inhibition of alloreactivation by a microbial composition wherein samples are cultured with (second test sample) and without (first test sample) test agents (e.g. see Example 60; meeting the limitations of claim 18). Berry teaches the use of serial dilutions (e.g. Examples 16 and 66; and [0169, 0691]; meeting the limitations of claim 23). Berry teaches pre-treatment including heat and ethanol (e.g. [0175]; meeting limitations found in instant claim 24). Berry teaches human subjects that are both healthy and have a disease condition (e.g. [0013, 0104, 0130, 0183, 0231, 0397]; meeting limitations found in instant claims 18, 31, 32 and 33). Berry teaches samples may be from a single individual or multiple donors (e.g. [0227, 0230]; meeting limitations found in instant claim 31). Berry teaches the multiple characteristics of the compositions comprising microbes may be tested including sensitive to environmental variables, pH resistance, bile acid resistance and/or antibiotic sensitivity either individually on a constituent-by-constituent basis or collectively as a bacterial composition comprised of multiple bacterial constituents (e.g. [0259-0272]; meeting limitations found in instant claims 18, 25, and 26).
Therefore, Berry anticipates the invention as claimed.
Pertinent Art
13. The following prior art, made of record and not relied upon, is considered pertinent:
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Conclusion
14. No claims are allowed.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY MAILLE LYONS whose telephone number is (571)272-2966. The examiner can normally be reached on Monday-Friday 8 am to 5 pm EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http: //www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached on (571)-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY MAILLE LYONS/ Examiner, Art Unit 1645
November 17, 2025