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 .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on Feb. 18, 2026 has been entered.
Claim Amendments
3. The claim amendments filed Feb 18, 2026 have been entered. Claims 1, 16 and 23 have been amended. Claims 4-5, 7-11, 13-15, 17-22, 25-27, 29-30, 33-38, 40-42, 44-47, 49-56, 58, 61-62, 64-66, 68-72 and 74-77 are canceled. Claims 1-3, 6, 12, 16, 23-24, 28, 31-32, 39, 43, 48, 57, 59-60, 63, 67, 73 and 78 are under consideration in this Office Action.
Withdrawn Grounds of Rejection
4. The rejection of claims 1-3, 6, 12, 16, 23-24, 28, 31-32, 39, 43, 48, 59, 63, 67 and 78 under 35 U.S.C. 102(a)(2) as being anticipated by Harris et al., (WO2014199115 published Dec. 18, 2018; priority to June 13, 2014) as evidenced Holcombe et al., (WO2020247959 published Dec. 10, 2020; priority to June 6, 2019) is withdrawn in view of Applicants amendments and arguments.
5. The rejection of claims 1-3, 6, 12, 16, 23-24, 28, 31-32, 39, 43, 48, 57, 59, 63, 67, 73 and 78 under 35 U.S.C. 103 as being unpatentable over Harris et al., (WO2014199115 published Dec. 18, 2018; priority to June 13, 2014) in view of Holcombe et al., [referred to as Holcombe I] (WO2020247959 published Dec. 10, 2020; priority to June 6, 2019) and Holcombe et al., [referred to as Holcombe II] (WO 2020160555 published August 6, 2020; priority to Feb. 1, 2019) is withdrawn in view of Applicants amendments and arguments.
6. The rejection of claims 1-3, 6, 12, 16, 23-24, 28, 31-32, 39, 43, 48, 57, 59-60, 63, 67, 73 and 78 under 35 U.S.C. 101 is withdrawn in view of Applicants amendments and arguments.
New Grounds of Rejection Necessitated By Applicants Amendments
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
7. Claims 1-3, 6, 12, 16, 23-24, 28, 31-32, 39, 43, 48, 57, 59-60, 63, 67 and 78
are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The claims recite the first intervention comprising administering one or more of a bacteriophage, a bacteriophage-associated protein and a bacteriophage lysin to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal. However it is unclear what the criteria is for determining when to administer the first intervention. There is no criteria for the comparison of the at least one test measure and one reference measure and the decision to administer the first intervention. Is the first intervention administered regardless of the comparison of the at least one test measure and one reference measure. Therefore, clarification is required to overcome the instant rejection.
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
8. Claims 1-3, 6, 12, 16, 23-24, 28, 31-32, 39, 43, 48, 59, 63, 67 and 78 are rejected under 35 U.S.C. 103 as being unpatentable over Harris et al., (WO2014199115 published Dec. 18, 2018; priority to June 13, 2014) in view of Simmons et al., (US 11, 998,479 published 2024-01-25; priority to Dec, 24, 2015).
Claim 1 recites a method for modifying an oral microbiome of a companion mammal, the method comprising: obtaining a test sample from an oral tissue or oral cavity of the companion mammal, the test sample including microbes of the oral microbiome, wherein the test sample is obtained after a preliminary intervention to modify the oral microbiome of the companion mammal:
analyzing the test sample to obtain test data for a plurality of taxa of the microbes of the oral microbiome of the companion mammal;
determining at least one test measure for each of one or more microbiome features based on the test data;
obtaining at least one reference measure for each of the one or more microbiome features, the at least one reference measure based on analysis of one or more reference samples from oral tissues or oral cavities of one or more reference companion mammals, the one or more reference samples including microbes of one or more reference oral microbiomes, the analysis of the one or more reference samples providing reference data for a plurality of taxa of microbes, the at least one reference measure based on the reference data; based on the at least one test measure and the at least one reference measure for the one or more microbiome features, administering an effective amount of a first intervention, the first intervention comprising administering one or more of a bacteriophage, a bacteriophage-associated protein and a bacteriophage lysin to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal.
Harris et al., teach an assay for use in a method of determining the oral health status of a canine animal by identifying certain bacteria present or absent in a sample taken from the animal, and applying the information set out herein for each identified bacteria to statistical models in order to determine the oral health status of the animal [abstract]. The diversity of bacterial species found in the canine oral microbiome has been reported using culture independent molecular methods from 51 dogs. Based on full length 16S rDNA Sanger sequencing, 353 taxa were identified; of these 80% were novel and only 16.4% were shared with the human oral microbiome [para 7]. Harris et al., described a study to identify the major species of bacteria present in the canine oral microbiome. This paper describes the major bacteria present in the canine oral microbiome [para 8]. Harris et al., method for determining the oral health status of a canine animal, the method comprising an assay, wherein the assay comprises means for identifying at least two bacteria in a sample taken from the animal and applying the information for each identified bacteria to statistical models in order to make a prediction of oral health status [para 11]. Harris et al., surveyed the oral microbiota of a sufficiently large canine cohort, at great enough depth to identify significant changes in bacterial taxa (phyla, genera and species) between dogs with healthy gingiva and those with gingivitis or mild periodontitis (PD1), and found important links between certain bacteria and different health states [para 15]. Thus teaching claim 3. A conscious test for oral health state enables more frequent monitoring of a pets oral health and provides encouragement for the use of preventative measures such as oral care treats and tooth brushing [para 17]; thus teaching preliminary interventions as recited by claims 6 and 28.
The sample from the animal to be tested in the animal may be dental plaque, gingival crevicular fluid saliva, or a mixture of any of these [para 19]; thus teaching instant claim 2. The presence of bacteria associated with disease can give an indication that the animal has gingivitis or periodontitis. The absence of a bacteria associated with disease is a good indication that the dog has good oral health. The presence of the health associated bacteria can help to determine how healthy is the mouth of the animal, although is less strong of an indicator than the presence of a disease associated bacterial species or genera. A binary test (determining presence or absence) can involve identifying just one incidence of a bacterial species or there may be a threshold, in that a particular bacterial species or genus is not considered present until the count for that particular species/genera reaches at least 3, or at least 5 or at least 7, or at least 9 [para 27]. Harris et al., teach indicators of taxonomic diversity and richness for multiple bacteria as recited by claim 12. A bacterial count may be determined by the number of times its sequence information is identified in a sample, by qPCR or by colony count. By counts, it is meant an absolute number, rather than a proportional number [para 28]. Additionally the step to determine the oral health status may comprise determining the proportion of total plaque bacteria of two or more of a bacteria species or genera [para 29]. Harris et al., teach indications of oral-health associated bacteria as recited by claim 24.
This information, combined with information regarding a particular animal obtained from the assay of the invention, and the use of statistical models known to the skilled person (examples of which are described herein) can lead to a prediction that is up to 83% accurate [para 39]. Once the information on presence/absence and/or proportion and/or counts of two or more bacteria has been obtained, one or more known statistical models can be used to predict the oral health status of the canine animal [para 41]. By determining the oral health status it is meant that the current status is determined, such as whether the mouth of the animal is in good oral health, has gingivitis or periodontitis at the time of taking the sample. The oral health status prediction may also encompass a prediction on whether a healthy mouth is likely to develop gingivitis or periodontitis, or whether gingivitis is likely to develop into periodontitis, based on the bacterial species or genera that are present/absent and the levels or counts of such bacteria. Thus, the assay of the present invention allows reliable prediction of the future oral health of the animal as well as providing information on the current oral health of the canine animal [para 43]. Thus teaching claim 63.
Harris et al’s method of improving or maintaining the oral health of an animal, the method comprising determining the oral health status of a canine animal using the assay according to the invention and providing to the animal a foodstuff or supplement which is formulated to improve or maintain oral health, depending on the oral health status that has been determined by way of the assay [para 45-46]. Thus teaching administering an effective amount of a first intervention to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal. Such food products are known in the art, such as those containing active ingredients to improve oral health or those designed to remove plaque by abrasion, analogous to regular tooth-brushing. The amount or frequency of the foodstuff or supplement can be determined depending on the result of the assay. The predicted future health of the animal can also be taken into account when determining how often such oral care foodstuffs should be provided [para 46].
Should the assay or method of the invention determine the likelihood that the oral health status is “P” (periodontitis/disease), the animal may be referred for a more thorough dental check to determine the next course of action [para 48]. If the assay determines that the oral health status is “not H” (i.e. not healthy), a further assay may be carried out to determine whether the status is Phot P. Alternatively or additionally, diet changes (as described above), dental chews, tooth brushing or a dental check may be recommended for the animal. A further test in 1 month, 3 months, 6 months or 12 months may also be recommended [para 49]. Administration of dental chews as prescribed by the directions meets the limitation of administering a first intervention as recited by claims 1 and 16 comprising a prebiotic and a chelating agent.
If the assay determines the likelihood of ‘health’, a further assay may be recommended in 1 month, 3 months, 6 months or 12 months and for the oral health regime (e.g. diet, dental chews, tooth brushing) to be maintained [para 0050]. The present invention also provides a method of determining the efficacy of an oral care product in a canine animal, the method comprising determining the oral health status of a canine animal using the assay of the invention; providing to the animal an oral care product for a certain period of time; and determining the oral health status of the animal using the assay of the invention after the period of time has elapsed [para 51]. Such a method enables the progress of the improvement of oral health to be monitored, without any invasive or risky procedures to the animal. More than one time point may be used, for example weekly, monthly, every two, three, four, five or six months, or annually. Thus teaching the second intervention as recited by claims 31. The amount of improvement of the oral health status may give an indication of the efficacy of the oral care product used in the method. Such oral care products or procedures may include foodstuffs, supplements, dental chews, tooth brushing, amongst others [para 52]; thus teaching claim 43. The chews contains the wheat starch which is a prebiotic fiber as recited by claim 32. The assay for determining the oral health status of a canine animal, the assay comprising means for identifying at least two bacteria selected from the list consisting of Escherichia coli, [para 47, Tables 3-4]. Thus teaching claim 78.
In healthy dogs Porphyromonas cangingivalis Canine Oral Taxon (COT)-109, Moraxella sp. COT-396 and Bergeyella zoohelcum COT-186 were the most abundant species. The latter two are also abundant in human health but the abundance of a Porphyromonad in healthy dogs is in contrast to the human oral microbiome where P. gingivalis has been synonymous with the red complex and human periodontal disease. The abundance of Porphyromonas, Moraxella and Bergeyella in healthy dogs was also observed in a recent 454 pyrosequencing study of 6 dogs [para 101]. Thus teaching the abundance of claim 39. FIG. 4b shows proportions of anaerobes for each sample by health status; health, gingivitis and mild periodontitis; black bars indicate mean proportion of species that are anaerobic with 95% confidence intervals [para 60]. Thus teaching claim 48. The means to identify the two or more bacteria present in the sample may be Quantitative PCR, sequencing or antibody binding. Fluorescent in situ hybridization may be used. Methods of extracting DNA or protein from bacteria are well known to one skilled in the art [para 20]. Thus teaching claim 59.
Therefore Harris et al., teach a method for modifying an oral microbiome of a companion mammal by administer a dental chew which modulates the canine’s oral microbiota, just as instantly claimed; but does not specifically recite administering one or more of a bacteriophage, a bacteriophage-associated protein and a bacteriophage lysin to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal.
Simmons et al., teach a method and system to address the adverse effects on an individual's oral microbiome with the objective of restoring gingival health [Abstract]. Oral plaque formation initiates often with colonizing bacteria, such as Streptococcus and Actinomyces, forming a supragingival biofilm. Over time, gram negative facultative (Fusobacteria) and obligate anaerobes (Porphyromonads) interact with the supragingival microbes, resulting in a predominantly anaerobic subgingival environment. Pathogenic bacteria species, such as Porphyromonas gingivalis, Tannerella forsythia and A. actinomycetemcomitans are implicated in the development of periodontal diseases, such as periodontitis, gingivitis, as well as in tooth decay via Streptococcus mutans, due to the populational increase in pathogenic bacteria either on the tooth surface (cariogenic bacteria) or within the sub-gingiva (periodontal pathogens) [para 9]. Oral conditions such as halitosis, a periodontal disease, or caries may be caused by a dysbiosis of microorganisms inhabiting the oral cavity. One or more bacterial species that are naturally occurring even in healthy individuals can become overly abundant to a point where those microorganisms reach pathogenic levels either in the entirety of the oral cavity or in isolated spaces, such as lesions or pockets between gum and tooth [para 16]. Other embodiments of the present invention provide an oral care composition that includes probiotics, prebiotics and postbiotics, including certain metabolites, that can be used to prevent a pathological condition, with still other embodiments including provision of antimicrobial peptides (AMPs) to an individual's oral cavity [para 18]. It should be understood that still other applications of certain embodiments are for the treatment of oral cavities of other animals, including mammals, and especially companion animals, such as canines and felines [para 64]. Just as recited by claim 73.
These can be presented and offered in the form of a capsule or tablet, especially one that includes a prebiotic, such as a fiber, preferably inulin [para 48]. The bioactive flavonoids that provide a multitude of actions in the oral cavity, including prebiotic feeding of beneficial bacteria, acting as a microbial substrate for production of additional health-promoting post-biotics, antimicrobial action of eliminating pathogenic bacteria and other undesired microorganisms, disrupting pathogenic biofilms, and anti-inflammatory and epithelial barrier strengthening actions in the buccal and gingival tissues [para 57]. Other embodiments of the invention that are directed to companion pets include the administration of desired bacterial compounds, etc, via including the same in an extruded chew, jerky chew, or other methods of delivering active components in a manner that requires mastication and shearing mechanical forces and that further aid in plaque removal [para 59]. The innovative method is directed to decreasing the relative representation of a specific strain of bacteria, preferably T. denticola and/or Prevotella, and/or S. mutans and/or Veilonella within a heterogenous population of oral bacteria, comprising contacting the heterogenous population of oral bacteria with a bacteriophage comprising a polynucleotide that expresses (a) an RNA-directed DNA-binding polypeptide comprising a nuclease module; and (b) a targeting module comprising a guide RNA, wherein the targeting module tethers the RNA-directed DNA-binding polypeptide to a target DNA sequence within, thereby producing a double-strand break within the target sequence, wherein the target sequence is unique to the specific strain of T. denticola and/or Prevotella and/or S. mutans and/or Veilonella bacteria [para 102].
Many bacterial species connected to oral disease, such as periodontitis and dental abscesses, can produce significant amounts of VOCs. Compounds such as butyric and propionic acid have been found in increased amounts from the gingival crevicular fluid and plaque of patients with chronic periodontitis. Bacterial volatile compounds have potential as biomarkers for oral infections, especially because they can be measured non-invasively from the exhaled breath or the salivary headspace. It is believed that morning breath contains the highest amounts of VOCs due to their accumulation and the undisturbed bacterial activity during a night's sleep. Changes in the oral pH affect the solubility of certain VOCs. Some compounds connected specifically to the subgingival anaerobes from the Treponema, Porphyromonas, Tannerella, and Prevotella genera, which increase in periodontitis compared to a healthy mouth, include methanol, pentanal, 3-penten-2-one, 1,3-pentadiene, methyl methacrylate, 3-methylbutyl propanoate, and 2-methyl-1-propanethiol [para 60].
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Harris et al., teach a method for modifying an oral microbiome of a companion mammal by administer a dental chew which modulates the canine’s oral microbiota, just as instantly claimed in combination with Simmons et al., teaching of administering bacteriophages to treat companion animals’ gingivitis, periodontitis and improve oral health by providing alternative and superior prevention and/or treatment options for oral diseases that address the root causes of such diseases rather than merely treating their symptoms. Additionally, no more than routine skill would have been required to incorporate Simmons et al., extruded chews which modify the oral microbiome of a companion animal, when Harris and Simmons et al., already teach intervention by the administration of chews; wherein the chews are known to improve the oral microbiome of a companion mammal by increasing the prevalence of good bacteria and decreasing the number of bacterial species associated with poor oral health or with disease. Therefore, no more than routine skill is required to incorporate companion animals. One of ordinary skill in the art would have a reasonable expectation of success by incorporating the teachings of Harris et al., to advantageously analyze bacteria associated with an oral disease or disorder such as periodontal disease, bacteria associated with good oral health, or both because performing an assay on the sample to measure an amount of a microbial nucleic acid to detect and/or to measure an amount of one or more bacteria indicative of the oral disease or disorder r is indicative of poor or worsening oral health; and treating or preventing the oral disease or disorder in the animal by administering a bacteriophage and recommending a change in oral hygiene or further intervention.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of modifying an oral microbiome, wherein there is no change in the identified oral diseases, bacterial markers, reference standards or interventions and administer bacteriophages, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
9. Applicant’s arguments, filed Feb 18, 2026, with respect to the rejection of claims 1-3, 6, 12, 16, 23-24, 28, 31-32, 39, 43, 48, 59, 63, 67 and 78 under Harris et al., as evidenced Holcombe et al., have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new grounds of rejection is made in view of Simmons et al., (US 11, 998,479 published 2024-01-25; priority to Dec, 24, 2015).
Applicants argue that the first intervention comprising administering one or more of a bacteriophage, a bacteriophage-associated protein and a bacteriophage lysin to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal is not taught by the Harris et al., reference. Therefore, the rejection is withdrawn in view of Applicants amendments.
In this case, Harris teach a first intervention comprising administering one or more chews to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal. Simmons et al., specifically teach administering a bacteriophage to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal by improving undesired malodors, improving host defense against true pathogens, gingivitis and periodontal diseases.
Claim Rejections - 35 USC § 103
10. Claims 1-3, 6, 12, 16, 23-24, 28, 31-32, 39, 43, 48, 57, 59-60, 63, 67, 73 and 78 are rejected under 35 U.S.C. 103 as being unpatentable over Harris et al., (WO2014199115 published Dec. 18, 2018; priority to June 13, 2014) and Simmons et al., (US 11, 998,479 published 2024-01-25; priority to Dec, 24, 2015) in view of Holcombe et al., [referred to as Holcombe I] (WO2020247959 published Dec. 10, 2020; priority to June 6, 2019) and Holcombe et al., [referred to as Holcombe II] (WO 2020160555 published August 6, 2020; priority to Feb. 1, 2019).
Harris et al., and Simmons et al., have been discussed above as teaching a method for modifying an oral microbiome of a companion mammal, the method comprising: obtaining a test sample from an oral tissue or oral cavity of the companion mammal, the test sample including microbes of the oral microbiome, wherein the test sample is obtained after a preliminary intervention to modify the oral microbiome of the companion mammal; analyzing the test sample to obtain test data for a plurality of taxa of the microbes of the oral microbiome of the companion mammal; determining at least one test measure for each of one or more microbiome features based on the test data; obtaining at least one reference measure for each of the one or more microbiome features, the at least one reference measure based on analysis of one or more reference samples from oral tissues or oral cavities of one or more reference companion mammals, the one or more reference samples including microbes of one or more reference oral microbiomes, the analysis of the one or more reference samples providing reference data for a plurality of taxa of microbes, the at least one reference measure based on the reference data; based on the at least one test measure and the at least one reference measure for the one or more microbiome features, administering an effective amount of a first intervention comprising administering one or more of a bacteriophage, a bacteriophage-associated protein and a bacteriophage lysin to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal.
However, Harris et al., and Simmons et al., do not teach the genetic material includes RNA, the test sample was preserved.
Harris et al., already described administering dental chews. Simmons et al., teach administering one or more of a bacteriophage, a bacteriophage-associated protein and a bacteriophage lysin to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal.
Holcombe I et al., describe administering an oral chew to a dog in an amount effective to improve the oral health of the dog in order to modulate the canine oral microbiota and improve the oral health of the dog [abstract]. The dental chew modulates the oral microbiota comprises increasing the prevalence of Prevotella sp. COT-282, Propionibacterium sp. COT-296, Catonella sp. COT-257, Peptostreptococcaceae bacterium FOT-054 and/or Corynebacterium mustelae. The chew modulates the oral microbiota by decreasing the number of bacterial species associated with poor oral health or with disease, or the prevalence or relative proportion of bacteria from bacterial species associated with poor oral health or disease, compared to the expected microbiota. The chew decreasing the prevalence of Fretibacterium sp. FOT-218, Neisseria canis, Anaerovorax sp. COT-125, Peptostreptococcaceae bacterium COT-030, Pelistega sp. COT-267, Bacteroidia bacterium COT-387, Desulfomicrobium orale and/or Helococcus sp. FOT-023.
Holcombe II et al., teach methods for testing the oral microbiome of an animal for presence of one or more bacteria, e.g, associated with an oral disease or disorder, such periodontal disease, good oral health, or both, in a sample collected from the animal [abstract]. Holcombe II et al., teach the use includes performing an assay on the sample to measure an amount of a microbial nucleic acid to detect one or more bacteria and/or to measure an amount of one or more bacteria in the sample [para 12]. The detection of the presence of bacteria or other markers can include measuring the amounts of bacteria or other markers, and the amounts can be compared to a scale that correlates the amounts of bacteria or other markers to the likelihood that the animal has oral disease or disorder e.g., periodontal disease or poor oral health. The intervention includes cleaning the mouth of the animal, removing plaque from the mouth of the animal, administering an antibiotic to treat an oral infection, providing dental chews to the animal or increasing frequency of dental chews, introducing or increasing frequency of tooth brushing, increasing use of dental diets, providing a dental treatment solution in water, or any combination thereof. In certain embodiments, the sample is a plaque sample [para 13]. The one or more bacteria is found in the oral microbiome of the animal comprises bacteria associated with an oral disease or disorder, bacteria associated with good oral health, or both. In some embodiments, the one or more bacteria includes Peptostreptococcaceae sp., volatile organic compound producing bacteria, or both. In particular embodiments, the one or more bacteria includes Peptostreptococcaceae XIII [G-1] sp., Peptostreptococcaceae COT-030, Peptostreptococcaceae COT-005/004, Peptostreptococcaceae COT-047, and/or Peptostreptococcaceae COT-019 [para 14].
The likelihood can be indicated as a percentage. For purpose of example and not limitation, the Cq score of a qPCR test that detects the nucleic acid (e.g., DNA or RNA) of bacteria associated with oral disease or disorder (e.g., periodontal disease) can be used to create the scale for calculating the likelihood that the animal has oral disease or disorder (e.g., periodontal disease) [para 117]. The amount of the one or more bacteria detected can be compared against a control dataset that provides the healthy range of amounts of the same bacteria in healthy animals of the same species. It can be determined that if the amount of the one or more bacteria detected is lower than the healthy amount in the control dataset, and/or if the amount of the one or more bacteria detected is greater than the healthy amount in the control data, the amount of said bacteria can be indicative of poor or worsening oral health in the animal. For example, in certain embodiments, when one sample is collected from the animal, the amount of the one or more bacteria detected in the sample is compared against the control dataset to determine if the one or more bacteria is indicative of poor or worsening oral health in the animal [para 94].
In some embodiments, the one or more bacteria includes bacteria associated with an oral disease or disorder, bacteria associated with good oral health, or both [para 12]. For example, in some embodiments, the one or more bacteria includes Peptostreptococcaceae sp., volatile organic compound producing bacteria, or both [para 12]. Therefore Holcomb II et al., teach analyzing volatile metabolites, just as recited by claim 60. In particular embodiments, the one or more bacteria includes Peptostreptococcaceae XIII [G-1] sp., Peptostreptococcaceae COT-030, Peptostreptococcaceae COT-005/004, Peptostreptococcaceae COT-047, and/or Peptostreptococcaceae COT-019. In further embodiments, the use further includes diagnosing a likelihood of the animal having an oral disease or disorder if the one or more bacteria detected is indicative of poor or worsening oral health. In some embodiments, the use further includes recommending a change in oral hygiene or an intervention if the one or more bacteria detected is indicative of poor or worsening oral health [para 12].
Just as Harris et al., and Simmons et al., taught interventions, Holcombe II et al., teach the intervention includes cleaning the mouth of the animal, removing plaque from the mouth of the animal, polishing the teeth of the animal, scaling the teeth to remove tartar or calculus, performing a gingivectomy, removing one or more diseased teeth from the mouth of the animal, administering to provide dental chews to the animal or increasing frequency of dental chews, introducing or increasing frequency of tooth brushing, increasing use of dental diets, providing a dental treatment solution in water, or any combination thereof. In certain embodiments, the sample is a plaque sample. In some embodiments, the animal is a companion animal. For example, in some embodiments, the animal is a dog or a cat [para 13]. Therefore, Holcombe II et al., teach oral microbiome of a companion mammal, including a cat, just as recited by claim 73. In some embodiments, the oral disease or disorder is periodontal disease, gingival stomatitis, odontoclastic resorptive lesions, and/or oral malodor [para 13].
When detecting bacteria methods of using the kits of the disclosed subject matter can include performing an assay on the sample to measure an amount of a microbial nucleic acid. The microbial nucleic acid can be a microbial DNA or RNA, e.g., a 16S ribosomal DNA (rDNA) or 16S ribosomal RNA (rRNA). In some embodiments, the disclosed methods include further measuring a host nucleic acid (e.g., DNA or RNA) in addition to the microbial nucleic acid [para 109]. Therefore, Holcomb II et al., teach the genetic material includes RNA just as recited by claim 57. Detecting the host nucleic acid can be useful, for instance, in predicting future risk of periodontal disease or possibility of other genetic conditions that can be a co-morbidity for periodontal disease. Various assays for identifying the presence of bacteria or other markers associated with an oral disease or disorder (e.g., periodontal disease) or good oral health are known in the art, such as quantitative polymerase chain reaction (qPCR) assays. The appropriate methods for performing such an assay can be ascertained by one of ordinary skill in the art [para 109]. Any of the disclosed methods include storing the sample collection device for transfer and analysis. As an ordinary skilled artisan would recognize, biological samples taken from an animal containing DNA are typically stored in a buffer solution. The buffer solution usually acts as a preservative, halts any further bacterial growth, and/or helps to maintain the integrity of the DNA, e.g., by inactivating any deoxyribonucleases that can be present in the sample and preventing DNA degradation. Buffer can also help to preserve DNA integrity during ambient temperature fluctuations that can affect DNA stability under certain conditions [para 103]; therefore teaching claim 67.
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Holcombe II et al’s cat RNA or DNA sample to Harris’ and Simmons’ method for modifying an oral microbiome of a companion mammal, to exchange companion animals like a dog for a cat when Simmons and Holcomb II et al., teach companion/domestic animals like dogs, and cats. Additionally, no more than routine skill would have been required to incorporate Simmons et al., extruded chews comprising a bacteriophage which modify the oral microbiome of a companion mammal, when Harris, Simmons and Holcombe II already teach intervention by the administration of dental chews; wherein the dental chews are known to improve the oral microbiome of a companion mammal by increasing the prevalence of good bacteria and decreasing the number of bacterial species associated with poor oral health or with disease. Furthermore, Holcombe II et al., teach RNA samples within a protective bacterial reagent such as a preserving buffer to yield higher average quantitation cycle (Cq) values marked by comparison group for quantitative polymerase chain reaction (qPCR) assays of samples. One of ordinary skill in the art would have a reasonable expectation of success by incorporating the teachings of Holcombe et al., to advantageously analyze bacteria associated with an oral disease or disorder such as periodontal disease, bacteria associated with good oral health, or both because performing an assay on the sample to measure an amount of a microbial nucleic acid to detect and/or to measure an amount of one or more bacteria indicative of the oral disease or disorder or is indicative of poor or worsening oral health; and treating or preventing the oral disease or disorder in the animal by recommending a change in oral hygiene or an intervention.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of modifying an oral microbiome, wherein there is no change in the identified oral diseases, bacteriophages, bacterial markers, reference standards or interventions, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
11. Applicant’s arguments, filed Feb. 18, 2026 with respect to the rejection(s) of claims 1-3, 6, 12, 16, 23-24, 28, 31-32, 39, 43, 48, 57, 59, 63, 67, and 73 under Harris et al., in view of Holcombe et al., have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new grounds of rejection is made in view of Simmons et al., (US 11, 998,479 published 2024-01-25; priority to Dec, 24, 2015).
In this case, the prior art teach a first intervention comprising administering one or more chews to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal. Simmons et al., specifically teach administering a bacteriophage to modify the plurality of taxa of the microbes of the oral microbiome of the companion mammal by improving undesired malodors, improving host defense against true pathogens, gingivitis and periodontal diseases. Therefore, Applicants arguments are not found persuasive and the rejection is maintained.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, it would have been prima facie obvious at the time of applicants’ invention to apply Holcombe II et al’s cat RNA or DNA sample to Harris’ and Simmons’ method for modifying an oral microbiome of a companion mammal, to exchange companion animals like a dog for a cat when Simmons and Holcomb II et al., teach companion/domestic animals like dogs, and cats. Moreover, no more than routine skill would have been required to incorporate Simmons et al., extruded chews comprising a bacteriophage which modify the oral microbiome of a companion mammal, when Harris, Simmons and Holcombe II already teach intervention by the administration of dental chews; wherein the dental chews are known to improve the oral microbiome of a companion mammal by increasing the prevalence of good bacteria and decreasing the number of bacterial species associated with poor oral health or with disease. Therefore, each and every limitations is taught by the prior art references.
Pertinent Art
12. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
Squires (2018) New Zealand Vet J 66(5), 229-235, 2018] teach bacteriophage therapy for management of bacterial infections in veterinary practice in companion animals.
Jensen et al., (US 11,844,720) teach a method to facilitate the growth of desired bacteria in a human's mouth to reduce the likelihood of dental caries and halitosis and other oral diseases, and for inhibiting oral biofilm formation, gingivitis, periodontitis and halitosis via the employment of one or more probiotic bacterial, bioactive flavonoid, and zinc compound compositions effective in providing prevention and treatment options. Specifically, the use of bacteriophages modified to attack particular bacteria, especially T. denticola and/or Prevotella, and/or S. mutans and/or Veilonella to reduce the populations of one or the other in the oral cavity.
Borie et al., (Arch Med Vet 46, 167-179 (2014) teach the application of bacteriophages, viruses that kill bacteria, as potential antimicrobial agents. Phage therapy in animal production, pets and experimental models of human infection have been discussed in veterinary medicine for 3 decades, with encouraging results in terms of reducing mortality, the severity of the clinical state and bacterial counts at tissue level. These benefits have been achieved thanks to increased knowledge of the biology of phages, better technology that allows their purification and their inherent advantages in terms of their safety for animals. Currently, phage research continues to open new horizons for both the medical industry and the food industry, considering the use of phages in the stages of “farm to fork”, with promising results if used as an intervention in animals since their arrival to the slaughter house.
Norris (US 4,891, 210 published 1990-01-02; priority to 1989-01-03). Norris teach A method of improved dental hygiene in which bacteriophages are used to reduce the number of harmful bacteria in the interdental spaces; wherein the phages are incorporated in toothpaste, toothpowder, dental floss, chewing gum, oral tablets, mouthwash, and/or sweets and candy.
Norris (US 4,957,686 published 1990-09-18; priority to 1990-02-06). Norris teach the use of bacteriophages to inhibit dental caries. S. Sanguis is the first colonizer of newly cleaned teeth and because other bacteria then attach to it, the formation of dental plaque is reduced on newly cleaned teeth by introducing into the mouth bacteriophages which are parasitic to S. Sanguis. Because S. Sanguis is the means of attachment of plaque forming bacterial colonies to tooth surfaces and forms 10-15% of the organisms in plaque, destruction of S. Sanguis by introduction of its parasitic bacteriophages will remove plaque from teeth surfaces. And removal of plaque containing acid forming bacteria and other harmful bacteria reduces the incidence of dental caries and other disease [abstract]. Phages are viruses which are parasitic to bacteria. In very simple terms a phage comprises a cell wall, an interior containing DNA and a tail. Each phage is specific to one kind of bacteria and does not attack other cells, bacterial or other. When the phage contacts the bacteria, the tail pierces the bacterial cell well and then acts as a conduit through which the phage DNA enters the bacterial cell. There, the DNA reorders the bacterial proteins to produce new phages. In approximately 30-60 minutes the bacterial cell wall bursts to release a multiplicity of new phages into the environment. These phages then contact other bacteria of the kind to which they are specific and destroy these, creating in the process an ever larger number of phages until the supply of bacteria on which to act runs out. Bacteriophages are well known and completely described in the prior art [Description of Invention]. The phages may be introduced into the mouth by tablet or liquid or spray, or may be contained in food or drink, or may be in toothpaste, dental floss or tooth cleaning powder, or other means. The phages should be introduced at intervals of not more than 2 days, the formation of a thick plaque layer taking 2-3 days. It may be advantageous to introduce the phages at night after tooth cleaning so that there is a minimum loss of phages by saliva action. Peoples secretion of saliva when sleeping is minimal. But it is highly probable that some of the phages would be absorbed into the surface of any plaque present in the mouth. Once deposited on and in the plaque the phages would find and destroy the bacteria to which they were parasitic. If only phages parasitic to S. Sanguis were used, the other bacteria would be unharmed. However, as the S. Sanguis bacteria were destroyed, the attachment of the plaque film to the teeth would be much weakened and they would no longer adhere to the tooth surfaces. As they are released from the tooth surface the acid forming bacteria can no longer produce a high acid concentration in proximity to the tooth enamel and dental caries would be inhibited [Description of Invention].
Conclusion
13. No claims allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571) 272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Peter Paras, can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/Primary Examiner, Art Unit 1645
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