DETAILED ACTION
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 .
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.
Election/Restrictions
Applicant’s election of Group I, drawn to claims 1-10, in the reply filed on Jul 30 2025 is 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)).
Claims 11-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on Jul 30 2025.
Claim Status
Claims 1-16 are pending.
Claims 11-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, as described above.
Claims 1-10 are objected to.
Claims 1-10 are rejected.
Priority
The instant Application claims domestic benefit to US provisional applications 62/826,497, 62/826,505, 62/826,479, and 62/826,515, each filed Mar 20 2019.
Applicant's claim for the benefit of a prior-filed application, PCT/US2020/025284, filed Mar 27 2020, is acknowledged.
Accordingly, each of claims 1-10 are afforded the effective filing date of Mar 20 2019.
Information Disclosure Statement
The information disclosure statements (IDS) filed on Sep 28 2021 and Jan 24 2024 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action.
The information disclosure statement filed Jan 17 2023 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. A translated copy of NPL reference 2 has not been provided. The IDS has been placed in the application file, but the information as indicated by strikethrough referred to therein has not been considered. It is noted that all other references have been considered.
Drawings
The Drawings submitted Sep 28 2021 are accepted.
Specification
The disclosure is objected to for the following informalities. It is noted that for purposes of the instant Office Action, any reference to the specification pertains to the specification as originally filed on Sep 28 2021.
Title
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The original title of “MICROBIOME BYPRODUCTS AND USES THEREOF” is not descriptive of the elected invention. The following title is suggested: “METHODS FOR TREATING A MICROORGANISM-RELATED CONDITION” or similar.
Disclosure
35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, requires the specification to be written in “full, clear, concise, and exact terms.” The specification is replete with terms which are not clear, concise and exact. The specification should be revised carefully in order to comply with 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112. Examples of some unclear, inexact or verbose terms used in the specification are:
The sentence “In a further aspect of the present disclosure, a platform for determining inhibitors of bacterial metabolites.” at p. 24, lines 1-2, is not a complete sentence;
The sentence “This new approach also aims at evading to knock-down human enzymes” at p. 24, lines 6-7, is not grammatically correct;
The semicolon in line 10, p. 24, after “(TMAO)” should be deleted; and
The sentence “Embodiments of a method can include a new pipeline to identify and target enzymes in is bacteria is proposed.” at p. 24, lines 14-15, is not grammatically correct.
It is noted that these are only a few examples of instances which require correction, and numerous others are present. Applicant is requested to please identify and correct other instances.
Appropriate correction for all objections to the specification is required.
Claim Objections
The claims are objected to for the following informalities:
Claims 1 and 4 recite “a target taxa” in the 3rd limitation. “Taxa” is the plural form of “taxon”. Therefore, the claims should be amended to recite “a target taxon”. Dependent claims 2-3 and 5-8 should also be amended to recite “the target taxon”.
Claims 9-10 each include a list of strains or species but are missing an “and” before the final item in each list.
Claim Rejections - 35 USC § 112
35 U.S.C. 112(a)
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.
Claims 9-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for identifying a blend of therapeutic microorganisms, the blend being configured to change an abundance of the target taxa in a community of microorganisms where the target taxa is associated with a microorganism-related condition, does not reasonably provide enablement for treating any microorganism-related condition with the strains or species recited in claims 9 and 10. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In In re Wands (8 USPQ2d 1400 (CAFC 1988)), the CAFC considered the issue of enablement in molecular biology. The CAFC summarized eight factors to be considered in a determination of "undue experimentation”. These factors include: (a) the quantity of experimentation necessary; (b) the amount of direction or guidance presented; (c) the presence or absence of working examples; (d) the nature of the invention; (e) the state of the prior art; (f) the relative skill of those in the art; (g) the predictability of the art; and (h) the breadth of the claims.
In considering the factors for the instant claims:
(a) In order to practice the claimed invention, one of skill in the art must be able to identifying a blend of therapeutic microorganisms comprising the strains recited in claims 9 and 10, the blend being configured to change an abundance of the target taxa in a community of microorganisms, where the target taxa is determined based on the relative abundance of or the co-occurrence between the microbial taxa with samples from people, among the population, with the microorganism-related condition and samples from people, among the population, without the microorganism-related condition, and then administer the blend to a patient with the microorganism-related condition with the intent, as set forth in the preamble, to treat the condition. The strains or species in claim 9 include Enterococcus faecium, Lactobacillus rhamnosus, Lactobacillus salivarius, Bifidobacterium adolescentis, Bifidobacterium animalis, Lactobacillus gasseri, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium pseudocatenulatum, Bifidobacterium stercoris, Lactobacillus reuteri, Lactobacillus fermentum, Pediococcus pentosaceus, Lactobacillus helveticus, Lactobacillus brevis, Lactococcus lactis, or Bacteroides xylanisolvens. The strains or species in claim 10 include Faecalibacterium prausnitzii, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Anaerostipes caccae, Anaerostipes rhamnosivorans, Eubacterium limosum, Eubacterium sp. ARC. 2, Subdoligranulum variabile, Akkermansia muciniphila, Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium crudilactis, Bifidobacterium dentium, Bifidobacterium pseudocatenulatum, Bifidobacterium stercoris, Bifidobacterium thermacidophilum, Methanobrevibacter smithii, Roseburia sp. 499, Bacteroides dorei, Bacteroides massiliensis, Bacteroides plebeius, Bacteroides sp. 35AE37, Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, Lactobacillus rhamnosus, Lactococcus lactis, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus gasseri, Lactobacillus reuteri, Lactobacillus fermentum, Pediococcus pentosaceus, Lactobacillus helveticus, or Lactobacillus brevis. For the reasons discussed below, there would be an unpredictable amount of experimentation required to practice the claimed invention.
(b) The specification as published provides guidance at [0059] for a therapeutic composition as an antibiotic recovery treatment that can include at least one or more of the following strains and/or species: Enterococcus faecium, Lactobacillus rhamnosus, Lactobacillus salivarius, Bifidobacterium adolescentis, Bifidobacterium animal's, Lactobacillus gasseri, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium pseudocatenulatum, Bifidobacterium stercoris, Lactobacillus reuteri, Lactobacillus fermentutn, Pediococcus pentosaceus, Lactobacillus helveticus, Lactobacillus brevis, Lactococcus lactis, Bacteroides xylanisolvens. The combination of all of them, or a subset of them, can be used for this treatment, diagnostics, and/or any suitable purpose. One or more of the described can include and/or be associated with all, or some of the following properties: pathogen inhibition, degradation of polysaccharides, degradation of mucin, short-chain fatty acids production, conjugation of linoleic acids production, production of GABA, indole production, modulation of immune response.
The specification as published provides guidance at [0060] for a therapeutic composition as an antibiotic recovery treatment that can include at least one or more strain and/or species: Faecalibacterium prausnitzii, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Anaerostipes caccae, Anaerostipes rhamnosivorans, Eubacterium limosum, Eubacterium sp. ARC.2, Subdoligranulum variabile, Akkermansia muciniphila, Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium crudilactis, Bifidobacterium dentium, Bifidobacterium pseudocatenulatum, Bifidobacterium stercoris, Bifidobacterium thermacidophilum, Methanobrevibacter smithii, Roseburia sp. 499, Bacteroides dorei, Bacteroides massiliensis, Bacteroides plebeius, Bacteroides sp. 35AE37, Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, Lactobacillus rhamnosus, Lactococcus lactis, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus gasseri, Lactobacillus reuteri, Lactobacillus fermentum, Pediococcus pentosaceus, Lactobacillus helveticus. Lactobacillus brevis. One or more of such species have all, or some of the following properties: pathogen inhibition, degradation of polysaccharides, degradation of mucin, short-chain fatty acids production, conjugation of linoleic acids production, production of GABA, indole production, and/or modulation of immune response.
The specification does not provide guidance for the strains or species recited in claims 9 and 10 being associated with any other microorganism-related condition.
(c) The specification as published provides a working example of changes in the relative abundance of the strains listed in [0060] to antibiotic consumption in TABLE A and co-occurrence probability of genus in samples from antibiotic non-consumers in TABLE B.
(d) The invention is drawn to treating any microorganism-related condition with the strains or species recited in claims 9 and 10.
(e) The state of the art of treating diseases with probiotics can be represented by McFarland et al. (Frontiers in Medicine, 5(124):1-14, 2018; newly cited). The reference makes clear that the probiotic strain-specificity and disease-specificity for efficacy are vital in choosing appropriate probiotics (abstract). McFarland provides evidence of strain and disease specificity for the efficacy of specific probiotic strains (abstract). McFarland demonstrates such strain specificity for specific conditions, such as adult antibiotic-associated diarrhe,a with, amongst others, Lactobacillus rhamnosus CLR2 and Lactobacillus reuteri 55730, while other Lactobacillus strains did not show efficacy (abstract; p. 4, col. 1, par. 3 through col. 2, par. 1; p. 4, col. 2, par. 4 through p. 8, col. 2, par. 1; p. 9, col. 2, par. 2 through p. 10, col. 2, par. 1; Figures 2-4; Table 2). McFarland makes clear that distinguishing the different probiotic products is challenging due to differences in their mechanisms-of-action, manufacturing processes, quality control of the product, and efficacy by different strain(s) (p. 1, col. 1, par. 2) and because the same probiotic strain or mixture of strains may be effective for one disease and yet not effective for other disease types despite diverse indications for use (p. 4, col. 2, par. 3; see also the Discussion and Conclusion on p. 10-11). There is no direction as to how to use specific strains or species to treat any microorganism-related condition without experimentation to determine whether the strain or species is correlated with that condition.
(f) The skill of those in the art of molecular biology and bioinformatics is high.
(g) The art is unpredictable because even different strains of the same species have varying efficacy for the same condition.
(h) The claims are broad because they are drawn to treating any microorganism-related condition with the strains or species recited in claims 9 and 10. However, the instant specification does not provide specific guidance to practice these embodiments. As such, the skilled practitioner would turn to the prior art for such guidance. However, the prior art makes clear that strains and species have specificity for disease efficacy and a single strain cannot treat every possible microorganism-related condition. Finally, said practitioner would turn to trial and error experimentation to determine whether the recited strains or species have efficacy for any given microorganism-related condition besides antibiotic consumption, as disclosed by the specification, which represents undue experimentation.
35 U.S.C. 112(b)
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.
Claim 8 is 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.
The term “high” in claim 8 is a relative term which renders the claim indefinite. The term “high” 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. Therefore, the metes and bounds of “one or more taxa having a high probability of co-occurrence” is unclear. The rejection may be overcome by clarifying the metes and bounds of the relative term “high”.
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 1-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, the claims are directed to methods, i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03].
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
The claims also recite a law of nature or a natural phenomenon. The MPEP at 2106.04(b) further explains that laws of nature and natural phenomena include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature.
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) as well as a law of nature or a natural phenomenon are as follows:
Independent claims 1 and 4: comparing a relative abundance of and co-occurrence between different microbial taxa in the set of samples; and
associating a change in the relative abundance of or the co-occurrence between the microbial taxa with samples from people, among the population, with the microorganism- related condition and samples from people, among the population, without the microorganism-related condition to determine a target taxa.
Independent claim 1: identifying a blend of bacteriophages, the blend being configured to remove the target taxa from a community of microorganisms.
Independent claim 4: identifying a blend of therapeutic microorganisms, the blend being configured to change an abundance of the target taxa in a community of microorganisms.
Dependent claims 2-3 and 5-6 recite further steps that limit the judicial exceptions in independent claim 1 and 4 and, as such, also are directed to those abstract ideas. For example, claims 2 and 5 further limit the target taxa to being directly correlated with an occurrence of the microorganism-related condition among the population; and claims 3 and 6 further limit the target taxa to co-occur with a taxon directly correlated with an occurrence of the microorganism-related condition among the population.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind and/or by mathematical operation because the method only requires a user to manually identify a blend of bacteriophages or therapeutic microorganisms based on desired effects on target taxa. Without further detail as to the methodology involved in “comparing”, “associating”, “determining”, and “identifying”, under the BRI, one may simply, for example, use pen and paper to compare the relative abundance of and co-occurrence between microbial taxa in a set of samples, determine a target taxa by associating changes in either the abundance or co-occurrence with a microorganism related condition, and identify a blend of bacteriophages or therapeutic microorganisms to change the target taxa. The step directed to “comparing a relative abundance” requires mathematical techniques as the only supported embodiments because the claims require a comparison of numbers, which is an inherently mathematical technique.
The claims also recite a natural relationship between a blend of bacteriophages or therapeutic microorganisms and their effect on the presence or abundance of the target taxa. Therefore, the claims recite a law of nature or a natural phenomenon.
Therefore, claims 1 and 4 and those claims dependent therefrom recite an abstract idea and a law of nature/natural phenomenon [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Independent claims 1 and 4: detecting microorganisms in a set of samples collected from a population; and
administering a therapeutic composition comprising the blend to the patient with the microorganism-related condition.
Dependent claims 7-10 recite steps that further limit the recited additional elements in the claims. For example, claim 7 further limits the blend to up-regulate the abundance of the target taxa by directly repopulating the target taxa; claim 8 further limits the blend to up-regulate the abundance of the target taxa by repopulating one or more taxa having a high probability of co-occurrence with the target taxa; and claims 9-10 further limit the blend to specific strains or species.
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to data gathering, such as “detecting” microorganisms in a set of samples, perform functions of collecting the data needed to carry out the judicial exceptions. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
Those steps directed to “administering a therapeutic composition comprising the blend to the patient with the microorganism-related condition” recites a treatment step which is not particular and is instead merely instructions to “apply” the exception in a generic way. The claims recite administering a therapeutic composition to patient that is not tied to any practical disease, condition, or therapeutic context. It is further noted that the claims do not require determining the presence or abundance of the target taxa in the patient to whom the treatment is administered. Therefore, the treatment is not directly linked to the patient, the only link being that the patient has the microorganism-related condition which has been associated with the target taxa. 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) (see MPEP 2106.04(d)(2)).
The specification does not provide a clear explanation for how the additional elements provide improvements. Therefore, the additional elements do not clearly improve the functioning of a computer, or comprise an improvement to any other technical field. Further, the additional elements do not clearly affect a particular treatment; they do not clearly require or set forth a particular machine; they do not clearly effect a transformation of matter; nor do they clearly provide a nonconventional or unconventional step (MPEP2106.04(d)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, the prior art to Arnold et al. (Trends in Microbiology, 2016, 24(11):887-901; newly cited) discloses that detecting microorganisms in samples and administering bacteriophage or therapeutic microorganisms (i.e., probiotics and fecal microbiota transplantation) to patients are data gathering and “apply it” elements that are routine, well-understood and conventional in the art (see the abstract, “Trends” section on p. 887; p. 897, par. 2; Box 3; Table 1; entire document is relevant). Arnold additionally discusses the use of specific probiotics species recited in claims 9-10 as being routine, well-understood and conventional in the art (Lactobacillus rhamnosus; see p. 896). It is further noted that the specification does not disclose any particular methods for “detecting” microorganisms in a sample, and is therefore considered to be able to be achieved by any means known to one skilled in the art. As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, the instant claims are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-10 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Apte et al. (US 2016/0110515; cited on the Sep 28 2021 IDS).
Claims 1 and 4 disclose a method for treating a microorganism-related condition in a patient.
Apte discloses a method for diagnosing and treating an immune microbial dysfunction in a subject (abstract). Apte, indicated by the open circles, teaches the instant features, indicated by the closed circles, as follows. Instantly claimed elements which are considered to be equivalent to the prior art teachings are described in bold for all claims.
The method of claims 1 and 4 comprises:
detecting microorganisms in a set of samples collected from a population;
Apte teaches receiving an aggregate set of biological samples from a population of subjects and generating at least one of a microbiome composition dataset and a microbiome functional diversity dataset for the population of subjects (abstract; [0013; 0019-0040]; FIG. 2).
comparing a relative abundance of and co-occurrence between different microbial taxa in the set of samples;
Apte teaches that compositional and functional features of the dataset can include measured relative abundances of microorganisms across different taxa [0023; 0040; 0047-0049]. Apte teaches determining taxonomic variation about changes in abundance of a taxon, which affects abundance of other taxa (i.e., co-occurrence) [0040]. Apte teaches performing statistical analyses on the features (i.e. comparing) of similarities and/or differences between a first group of subjects exhibiting a target state associated with the immune microbial dysfunction, and a second group of subjects not exhibiting the target state [0047]. Apte also teaches that features can include descriptions of interactions between different taxonomic groups (i.e., co-occurrence) [0039].
associating a change in the relative abundance of or the co-occurrence between the microbial taxa with samples from people, among the population, with the microorganism- related condition and samples from people, among the population, without the microorganism-related condition to determine a target taxa;
Apte teaches generating a characterization of the immune microbial dysfunction based upon features extracted from at least one of the microbiome composition dataset and the microbiome functional diversity dataset (abstract). Apte teaches performing statistical analyses to assess a set of microbiome composition features and microbiome functional features having varying degrees of abundance in a first subset of the population of subjects exhibiting the immune microbial dysfunction and a second subset of the population of subjects not exhibiting the immune microbial dysfunction in order to identify specific features in the first subset (i.e., target taxa) [0047].
identifying a blend of bacteriophages, the blend being configured to remove the target taxa from a community of microorganisms (claim 1); identifying a blend of therapeutic microorganisms, the blend being configured to change an abundance of the target taxa in a community of microorganisms (claim 4); and
Apte teaches based upon the characterization, generating a therapy model configured to correct the immune microbial dysfunction, and at an output device associated with the subject, promoting a therapy to the subject based upon the characterization and the therapy model (abstract; [0013-0017; 0019; 0045; 0053; 0055; 0058; 0061; 0065-0083]). Apte teaches that the predicted therapies may include phage-based therapy (i.e., bacteriophages) and probiotics (i.e., therapeutic microorganisms) [0065]. Apte teaches an example of a bacteriophage-based therapy, one or more populations of bacteriophages (i.e., a blend) specific to a certain bacteria represented in a subject with the immune microbial dysfunction can be used to down-regulate or otherwise eliminate populations of the certain bacteria in order to reduce the size of the undesired population [0014; 0065-0066; 0081]. Apte teaches an example of probiotic therapies comprising a combination of multiple types of bacteria (i.e., a blend) [0071] that will positively adjust a subject’s microbiome [0072]. Apte teaches a probiotic therapy that selectively supports a population size increase of a desired taxon associated with correction of the immune microbial dysfunction (claim 19).
administering a therapeutic composition comprising the blend to the patient with the microorganism-related condition.
Apte teaches administering the therapeutic measure [0082].
Regarding instant claims 2-3 and 5-6, Apte teaches claims 1 and 4 as described above. Claims 2 and 5 further add that the target taxa comprises a taxon directly correlated with an occurrence of the microorganism-related condition among the population. Claims 3 and 6 further add that the target taxa comprises a taxon co-occurring with a taxon directly correlated with an occurrence of the microorganism-related condition among the population.
Apte teaches performing statistical analyses to assess a set of microbiome composition features and microbiome functional features having varying degrees of abundance in a first subset of the population of subjects exhibiting the immune microbial dysfunction and a second subset of the population of subjects not exhibiting the immune microbial dysfunction in order to identify specific features in the first subset (i.e., a taxon directly correlated with an occurrence of the microorganism-related condition among the population as in claims 2 and 5) [0047]. Apte teaches determining taxonomic variation about changes in abundance of a taxon, which affects abundance of other taxa [0040], as well as analyzing features which include descriptions of interactions between different taxonomic groups [0039] (i.e., a taxon co-occurring with a taxon directly correlated with an occurrence of the microorganism-related condition among the population as in claims 3 and 6).
Regarding instant claims 7-8, Apte teaches claim 4 as described above. Claim 7 further adds that the blend is configured to up-regulate the abundance of the target taxa by directly repopulating the target taxa. Claim 8 further adds that the blend is configured to up-regulate the abundance of the target taxa by repopulating one or more taxa having a high probability of co-occurrence with the target taxa.
Apte teaches an example of probiotic therapies comprising a combination of multiple types of bacteria [0071] that will positively adjust a subject’s microbiome [0072]. Apte teaches a probiotic therapy that selectively supports a population size increase of a desired taxon associated with correction of the immune microbial dysfunction (claim 19). As Apte teaches determining taxonomic variation about changes in abundance of a taxon, which affects abundance of other taxa (i.e., co-occurrence) [0040] and analyzing features which include interactions [0039], it is considered that the probiotic therapies of Apte read on up-regulating the abundance of the target taxa by both directly repopulating the target taxa (see also [0072]), as in claim 7, and repopulating one or more taxa having a high probability of co-occurrence with the target taxa, as in claim 8.
Regarding instant claims 9-10, Apte teaches claim 4 as described above. Claim 9 further adds that the blend comprises a strain or species selected from the group consisting of Enterococcus faecium, Lactobacillus rhamnosus, Lactobacillus salivarius, Bifidobacterium adolescentis, Bifidobacterium animalis, Lactobacillus gasseri, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium pseudocatenulatum, Bifidobacterium stercoris, Lactobacillus reuteri, Lactobacillus fermentutn, Pediococcus pentosaceus, Lactobacillus helveticus, Lactobacillus brevis, Lactococcus lacus, Bacteroides xylanisolvens. Claim 10 further adds that the blend comprises a strain or species selected from the group consisting of: Faecalibacterium prausnitzii, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Anaerostipes caccae, Anaerostipes rhamnosivorans, Eubacterium limosum, Eubacterium sp. ARC. 2, Subdoligranulum variabde, Akkermansia muciniphila, Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium crudilactis, Bifidobacterium dentium, Bifidobacterium pseudocatenulatum, Bifidobacterium stercoris, Bifidobacterium thermacidophilum, Methanobrevibacter smithii, Roseburia sp. 499, Bacteroides dorei, Bacteroides massiliensis, Bacteroides plebeius, Bacteroides sp. 35AE37, Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, Lactobacillus rhamnosus, Lactococcus lactis, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus gasseri, Lactobacillus reuteri, Lactobacillus fermentum, Pediococcus pentosaceus, Lactobacillus helveticus, Lactobacillus brevis.
Apte teaches the use of Lactobacillus rhamnosus and Lactococcus lactis as probiotic therapies [0073].
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
A. Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 10-12, and 18-19 of U.S. Patent No. 9703929 in view of Apte et al. (US 2016/0110515; cited on the Sep 28 2021 IDS).
Regarding instant claims 1 and 4, reference patent claims 1 and 10 disclose instant limitations 1-2 and 4 except a relative abundance in limitations 1-2, which reference claims 2 and 11 disclose, and actually administering the blend in limitation 4. It is considered that “generating a characterization of the immune microbial dysfunction” in reference claims 1 and 10 reads on a co-occurrence between different microbial taxa in instant claims 1 and 4 because the characterization encompasses analyzing the microbiome composition and interactions therein, as recited in reference claims 2 and 11-12. Reference claim 18 discloses instant limitation 3 of claim 1 and reference claim 19 discloses instant limitation 3 of claim 4.
The reference patent does not disclose actually administering the blend.
However, the prior art to Apte, which is the PGPub of the reference patent, discloses administering the therapeutic measure [0082].
Regarding claims 1 and 4, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the reference patent and Apte because both references disclose methods for characterizing and treating microbiome dysbiosis. The basic technique of administering a treatment would have yielded no more than the predictable outcome of modifying the patient’s microbiome which one of ordinary skill would have expected to achieve with this common tool of the trade after identifying dysbiosis in a patient.
Regarding instant claims 2-3 and 5-6, reference patent claims 1-2, 10-11, and 18-19 disclose the limitations of the instant claims because the features are determined based on a characterization of interactions between different taxonomic groups, which reads on a taxon directly correlated or a taxon co-occurring with a taxon directly correlated with an occurrence of the condition as instantly claimed.
Regarding instant claims 7-8, reference claims 1-2, 10-11, and 19 disclose the limitations of the instant claims because the therapies of claim 19 increase the population size of a desired taxon associated with the immune microbial dysfunction, which could be determined based on a characterization of interactions between different taxonomic groups, which reads on directly up-regulating a target taxa or indirectly by repopulating taxa which co-occur with the target taxa as instantly claimed.
Regarding instant claims 9-10, the reference patent does not disclose these limitations.
However, the prior art to Apte, which is the PGPub of the reference patent, discloses the use of Lactobacillus rhamnosus and Lactococcus lactis as probiotic therapies [0073].
Regarding claims 9-10, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the reference patent and Apte because both references disclose methods for characterizing and treating microbiome dysbiosis. The basic technique of treating patients with Lactobacillus rhamnosus or Lactococcus lactis would have yielded no more than the predictable outcome of modifying the patient’s microbiome which one of ordinary skill would have expected to achieve with this common tool of the trade after identifying dysbiosis in a patient.
B. Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-12, 19-20, and 22 of U.S. Patent No. 9710606 in view of Apte et al. (US 2016/0110515; cited on the Sep 28 2021 IDS).
Regarding instant claims 1 and 4, reference patent claim 11 discloses instant limitations 1-2 and 4 except a relative abundance and co-occurrence in limitation 2, which reference claim 12 discloses, and actually administering the blend in limitation 4. It is considered that “transforming at least one of the microbiome composition dataset and the microbiome functional diversity dataset into a characterization model” in reference claim 11 reads on a co-occurrence between different microbial taxa in instant claims 1 and 4 because the characterization encompasses analyzing the microbiome composition and interactions therein, as recited in reference claim 12. Reference claim 20 discloses instant limitation 3 of claim 1 and reference claim 22 discloses instant limitation 3 of claim 4.
The reference patent does not disclose actually administering the blend.
However, the prior art to Apte discloses a method for diagnosing and treating an immune microbial dysfunction in a subject (abstract). Apte discloses administering the therapeutic measure [0082].
Regarding claims 1 and 4, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the reference patent and Apte because both references disclose methods for characterizing and treating microbiome dysbiosis. The basic technique of administering a treatment would have yielded no more than the predictable outcome of modifying the patient’s microbiome which one of ordinary skill would have expected to achieve with this common tool of the trade after identifying dysbiosis in a patient.
Regarding instant claims 2-3 and 5-6, reference patent claims 11-12 disclose the limitations of the instant claims because the features are determined based on a characterization of interactions between different taxonomic groups, which reads on a taxon directly correlated or a taxon co-occurring with a taxon directly correlated with an occurrence of the condition as instantly claimed.
Regarding instant claims 7-8, reference claims 11-12, 19, and 22 disclose the limitations of the instant claims because the therapies of claim 22 increase the population size of a desired taxon associated with the immune microbial dysfunction, which could be determined based on a characterization of interactions between different taxonomic groups, which reads on directly up-regulating a target taxa or indirectly by repopulating taxa which co-occur with the target taxa as instantly claimed.
Regarding instant claims 9-10, the reference patent does not disclose these limitations.
However, the prior art to Apte discloses the use of Lactobacillus rhamnosus and Lactococcus lactis as probiotic therapies [0073].
Regarding claims 9-10, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the reference patent and Apte because both references disclose methods for characterizing and treating microbiome dysbiosis. The basic technique of treating patients with Lactobacillus rhamnosus or Lactococcus lactis would have yielded no more than the predictable outcome of modifying the patient’s microbiome which one of ordinary skill would have expected to achieve with this common tool of the trade after identifying dysbiosis in a patient.
C. Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-12 and 19 of U.S. Patent No. 10073952 in view of Apte et al. (US 2016/0110515; cited on the Sep 28 2021 IDS).
Regarding instant claims 1 and 4, reference patent claim 10 discloses instant limitations 1-2 and 4 except a relative abundance and co-occurrence in limitation 2 and actually administering the blend in limitation 4. Reference claims 11-12 disclose the relative abundance. Reference claim 19 discloses instant limitation 3 of claim 4. The reference patent does not disclose instant limitation 3 of claim 1.
The reference patent does not disclose a co-occurrence, actually administering the blend in claims 1 and 4, or the instant limitation 3 of claim 1.
However, the prior art to Apte discloses a method for diagnosing and treating an immune microbial dysfunction in a subj