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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found
in a prior Office action.
This Action is in response to the papers filed on March 6, 2026 for a Request for Continued Examination. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 March 6, 2026 has been entered.
Pursuant to the amendment to the claims filed on January 21, 2026, claims 1-4, 6-18 and 21-22 are currently pending of which claims 1, 21 and 22 have been amended. No claims have been added and no claims have been added.
The restriction requirement between Groups I-V was previously made FINAL, wherein claims 2, 11-18 were previously withdrawn in the Office Action dated April 21, 2025.
Therefore, claims 1, 3-4, 6-10 and 21-22 are currently under examination to which the following grounds of rejection are applicable.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/IL2020/050742, filed July 2, 2020. Applicant’s claim for the benefit of a prior-filed parent provisional application 62/869,616 filed on July 2, 2019 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is July 2, 2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 17, 2026 has been filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or an official IDS, they have not been considered.
Response to Arguments
Withdrawn Objections/Rejections in response to Applicants’ arguments or amendments:
Claim Rejections - 35 USC § 112
In view of Applicants’ amendment to the claims dated January 21, 2026, wherein claims 1, 21 and 22 have been amended, the rejection to claims 1, 21 and 22 rejected under 35 U.S.C. 112(b) as being indefinite have been withdrawn.
Claim Rejections - 35 USC § 103
In view of Applicants’ amendment to the claims dated January 21, 2026, wherein claims 1, 21 and 22 have been amended, the rejection to claims 1, 3-4, 6-10 rejected under 35 U.S.C. 103 as being unpatentable over Sasson et al., in view of Li et al, Lamb et al., and Benedet et al., have been withdrawn.
In view of Applicants’ amendment to the claims dated January 21, 2026, wherein claims 1, 21 and 22 have been amended, the rejection to claims 121, and 22 rejected under 35 U.S.C. 103 as being unpatentable over Sasson et al., in view of Li et al, Lamb et al., and Benedet et al. as applied to claim 1, and further in view of Roume, have been withdrawn.
The withdrawn rejections are in view of the amendments to the claims wherein
Applicants’ arguments are moot in view of the withdrawn rejection. A response to any argument pertaining to a new or maintained rejection can be found below.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-4, 6-10, 21, and 22 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:
(a) analyzing the microbiome of a ruminating animal for a presence of said at least one hereditable bacteria, wherein said at least one hereditable bacteria has a 16S rRNA gene comprising a sequence as set forth in SEQ ID NO: 20, and wherein the ruminating animal is a cow, it does not reasonably provide enablement for the entirety of the scope of breeding recited in claim 1 based on the presence of at least one hereditable bacteria whose presence positively correlates with a plasma Beta-Hydroxybutyric Acid (BHB) level. In particular, the Specification only supports the heritable bacterial strain as one that comprises a 16S rRNA gene comprising a sequence as set forth in SEQ ID NO:20 as it is the only strain is positively correlated with BHB, and furthermore the ruminating animal being a cow.
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.
The factors to be considered in determining whether undue experimentation is required are summarized in In re Wands, 858 F.2d 731, 737, 8 U.S.P.Q.2d 1400, 1404 (Fed. Cir. 1988) (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of working examples; and (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
(1) the breadth of the claims; (2) the nature of the invention: The claims are directed to a method of breeding a ruminating animal having a microbiome which comprises at least one hereditable bacteria whose presence positively correlates with a plasma Beta-Hydroxybutyric Acid (BHB) level, the method comprising:
(a) analyzing in the microbiome of the ruminating animal for a presence of said at least one hereditable bacteria, wherein the presence of said at least one hereditable bacteria is indicative as to whether progeny of the ruminating animal has the plasma BHB level; and
(b) breeding the ruminating animal that has the at least one hereditable bacteria.
It is noted the claim does not recite in relation to step (a) the steps/analysis for determining the relationship between heritable bacteria and plasma BHB levels, the analysis for the determination of which bacteria comprised in the ruminant microbiome are heritable, the particular ruminant subject, and importantly the specific bacterial strain identified that is positively correlated the to the plasma BHB level claimed (refer to the 112(b) rejection listed above regarding the BHB level). Thus, the claims are not fully enabled.
(6) the amount of direction provided by the inventor; (7) the existence of working examples: The specification provides little guidance over the breadth of the pending claims. Starting on page 24 of the Specification, the materials and methods pertaining the claimed invention are described. The population evaluated was 1016 cows (subset of ruminants) all of which were between 10 and 40 weeks postpartum, have received the standard diet for at least 14 days, and had no health issue in the current lactation. Therefore, the sample pool was only female cows of a certain age, health, and diet. The section further expands on the diet of the cows in addition to the samples collections with corresponding tests that were conducted with the samples. Quantitative PCR of 16S and 18S rRNA genes was conducted to determine bacterial abundance, and bovine genotyping was conducted with blood samples wherein DNA was extracted and quantified for SNP genotyping. Pages 29 -35 describe the statistical analyses with corresponding software/algorithms employed to determine: microbial populations, correlation of microbial populations to phenotypes, correlation of microbial populations to genotypes, prediction of phenotypes based on either microbial populations and/or diet, and microbial heritability.
The Results provided starting on page 35, describe the findings “a core group of rumen microbes (512 species-level microbial operation taxonomic units (OTUs), 454 prokaryotes, 12 protozoa and 46 fungi) present in at least 50% of animals, within each of the seven farms studied. The group comprised eleven prokaryotic orders, one fungal and two protozoal orders that share some similarity with published core microbial communities ( 4,15)… The results demonstrate once again, however, that this microbial community is representative of ruminants in general, especially with respect to bacterial and protozoal species. This core community is significantly enriched in Bacteroidales, Spirochetales and the WCHB 1-4 order. The core microbiome consists of less than 0.25% of the overall microbial species pool (512 out of 250,000 OTUs), yet it is highly abundant, representing 30-60% of the overall microbiome.” The hereditable bacteria that are associated with traits are listed in Table 1. Table 2 is similar except it is directed to all bacteria correlated with an identified trait, and not required to be heritable bacteria for which the claim is directed. Table 3 lists all the heritable bacteria identified in the study. The findings reveal that a particular strain of Prevotella (SEQ ID NO: 20) is the only predicted heritable bacteria that is shown to be positively correlated with plasma BHB, and no other heritable bacteria across the ruminants share this characteristic. The conclusion describes the results are likely to be applicable to beef animals and other ruminant species; however, this statement is unsupported based on the lack of other ruminant types examined. There are no studies showing the heritable bacteria with corresponding phenotype, i.e. higher plasma BHB, as being inherited across generations to support the bacteria as being heritable. Furthermore, there are no findings that there are other heritable bacteria across ruminants as having a positive correlation with plasma BHB other than the specific Prevotella strain identified as SEQ ID NO: 20.
(3) state of the prior art: Sasson et al (of record) describes the relationship between rumen microbiome and ruminant genetics as being poorly understood based on the lack of literature. In contrast, the connection between rumen microbiome and ruminant diet with corresponding rumen traits are well-established and remain studied. Sasson describes that one study suggested that host genetics may play a role in rumen microbiome. Another study shared this finding when comparing the archaeon/bacterium ratios in rumen microbiomes. The last study revealed that hybrid offspring have different microbial compositions than their parents, and select pathways were enriched and correlated with the abundance of select bacterial species, one of which is Prevotella (Introduction).
Sasson analyzed the relationship between ruminants’ genetics and physiology and the rumen microbiome structure, composition, and metabolism, in which a population of cows were analyzed by combining rumen microbiota data in combination with select phenotypes with genotypic data from a subset of these cows. In relation to findings Sasson states, “We identified 22 operational taxonomic units (OTUs) whose abundances were associated with rumen metabolic traits and host physiological traits and which showed measurable heritability. The abundance patterns of these microbes can explain high proportions of variance in rumen metabolism and many of the host physiological attributes such as its energy-harvesting efficiency.” (abstract)).
Sasson further states, “Intriguingly, we found that the heritable bacteria contain higher proportions of microbes correlated with host traits and with rumen metabolic parameters (Fig. 4A and B). These findings suggest that host genetic variation can have a measurable impact on physiological traits of the host as well as on rumen metabolism by potentially modulating the abundances of different groups of rumen microbes. These findings indicate that host genetics are associated with specific rumen bacteria, which are potentially more prone to influence rumen metabolism and host physiology. Notably, the metabolites and host traits that were found to be correlated with heritable bacteria were also connected by their metabolism. This could be seen in the correlation values of methane production, propionate/acetate ratio, lactate, propionate, and butyrate, as well as energy-harvesting efficiency of the host (represented as RFI), which are correlated with the heritable bacteria.” (p 8, par 3).
Sasson concludes that “Our observations further strengthen the notion of a triangular relationship among the host genotype, rumen bacteria, and host traits. Although it is tempting to speculate that host genetics mediate control of physiological attributes via rumen metabolism, the relationship between these parameters is still to be determined. To target these concerns, future experiments with a larger sample size should be performed to obtain more accurate heritability estimations for both microbes and host traits. Such accuracies could then be utilized to compare heritability estimates of microbes and host traits and suggest cases of the direct causal roles in cases of equal scores. A more direct approach to tackle the question of causality would be to apply transplantation of rumen microbes in different host genetic back-grounds.” (Conclusion).
Sasson does not teach in relation to step (a) the particular heritable bacteria being related to plasma BHB, and for step (b) breeding the animal that has the desirable hereditable bacteria. However, breeding techniques. i.e. artificial insemination, are well-known in the art.
Li et al. (of record) estimated the heritability of rumen microbial taxonomic features, and further identified genetic components associated with specific rumen microbial taxa. “Multiple factors, including breed, sex, and diet were identified to drive the variation of rumen microbiota among animals. The findings on moderate heritability estimates for rumen microbial taxonomic features and the identified microbial taxa associated SNPs from GWAS show direct evidence that rumen microbial colonization in beef cattle can be affected by host additive genetic effects and genotypes.” (Conclusion). In conclusion, it was determined that some rumen microbial features are heritable and could be influenced by host genetics, highlighting a potential to manipulate and obtain a desirable and efficient rumen microbiota using genetic selection and breeding.” (abstract).
In summary, the prior art supports the analysis of rumen microbiomes for the identification of heritable bacteria that correspond with host traits; however the prior art, as supported by Sasson, remains limited. The current claims are directed to the identification of heritable bacteria in ruminant microbiomes that are positively correlated to plasma BHB levels, yet the claims do not recite any particular method steps for such analysis, with corresponding validation that the identified bacteria are heritable across the large scope of ruminants encompassed, and remain positively correlated with plasma BHB levels. Moreover, the claim is directed any heritable bacteria, yet the disclosure only supports a particular species of Prevotella as listed on Table 1 (SEQ ID NO: 20). Lastly, the microbiome studies of other ruminating is more limited than cows, and there is no indication that the findings of cow rumen microbiomes would extend to other ruminant species.
(4) the level of one of ordinary skill: There is a high level of skill required.
(5) the level of predictability in the art: The art is unpredictable. As described above, microbiome research connecting ruminant host genetics and traits with microbiome members remains a new field. Therefore, there remains much to be learned by these relationships, and what can and cannot be inferred based on findings.
(8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure: The skilled artisan would be required to perform extensive experimentation in order to practice the claimed invention. The instant specification does not reduce to practice the claimed invention; the instant specification does not provide specific guidance on how to reasonably predict what bacteria are heritable, and moreover which heritable bacteria are positively related to plasma BHB levels. There is not adequate information regarding, the particular equations or algorithms to make these determinations. Moreover, there is no support that the positive correlation extends to all ruminants, and more specifically within bovine to groups outside the tested groups of females that meet the aforementioned parameters. Finally, the findings only show a particular Prevotella species as meeting the criteria, and therefore the scope should reflect this finding, as opposed to including any heritable bacteria with such relationship despite this scope not being supported.
Conclusion:
When all of the Wands factors are considered together, they establish a prima facie case that the specification is not enabling for the full scope of claim 1. While a lack of a working embodiment cannot be a sole factor in determining enablement, the lack of any working examples, in light of the unpredictable nature of the art and the lack of direction applicants present, provides additional weight to the lack of enablement in consideration of the Wands factors as a whole. Thus, one of ordinary skill in the art would not have had a reasonable expectation of success in making or using the claimed invention in view of the current scope of the claims. Claims 3-4, 6-10 and 21-22 depend from claim 1. These dependent claims do not cure the deficiency in the independent claim and are rejected on the same basis.
Conclusion
Claims 1, 3-4, 6-10 and 21-22 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634