DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Remarks
The amendments and remarks filed on 03/16/2026 have been entered and considered. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. The rejections and/or objections presented herein are the only rejections and/or objections currently outstanding. Any previously presented objections or rejections that are not presented in this Office Action are withdrawn.
Claims 1-11 and 19-21 are pending.
Claim 10 is amended.
Claims 12-18 are canceled.
Claims 1-9 and 21 are withdrawn.
Claims 10-11 and 19-20 have been examined on the merits.
Priority
This application, U.S. Application number 18/628884, is a division of US application No. 14773887 filed on 09/09/2015, now US patent No. 11951138, which is a national stage entry of International Application Number PCT/IL2014/050277, filed on 03/13/2014.
Applicant’s claim for the benefit of a prior-filed application: U.S. provisional application No. 61782783 filed on 03/14/2013, under 35 U.S.C. 119(e) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AlA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, U.S. provisional application No. 61782783, fails to provide adequate support in the manner provided by 35 U.S.C. 112(a) for the base claim 10 and its dependent claims of this application, For the reasons of record (see pages 3-4 of the previous final office action). Accordingly, the claims 10-11 and 19-20 do not receive the benefit of the filing date of the provisional application. The effective filing date of instant claims is the filing date of the international application PCT/IL2014/050277, which is 03/13/2014.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/20/2026 and 03/25/2026 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97., and have been considered by the examiner.
Objections - Withdrawn
Objection to the claims 10 and 19 in the previous office action is withdrawn due to the amendment to the claims filed on 03/16/2026.
Rejections - Withdrawn
The rejection of Claims 10-11 and 19-20 under 35 U.S.C. 101, as the claims are directed to a judicial exception without significantly more, is withdrawn due to the amendment to the claims filed on 03/16/2026.
The rejection of Claims 10-11 and 19-20 under 35 U.S.C. 103 over Zhou et al. in view of Baker, Jami et al., Koike et al., and Henn et al. is withdrawn in favor of the rejections listed below.
Claim Objections
Claim 10 is objected to due to the recitation of “a a plurality of control healthy animals” at lines 9-10 of the claim. The term should be corrected to “a plurality of control healthy animals”. Appropriate correction is required.
Claim 11 is objected to due to the recitations of “said ruminating animal” and “said animal”. To be consistent with the base claim 10, these terms should be changed to “said candidate ruminating animal”.
Claim Rejections - 35 USC § 112(b), or 112, Second Paragraph
Claims 10-11 and 19-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 10 is indefinite due to the recitation of “said positive rumen microbiome reference signature of said control healthy animal” in the step (b) of the claim. It is noted that the recited “said control healthy animal” stands for a single animal. However, the step (b) previously defines “a positive rumen microbiome reference signature based on … a plurality of control healthy animals …” (emphasis added), and it does not define any positive reference signature based on a single control healthy animal. It is unclear which specific control healthy animal the recited “said control healthy animal” refers to; and it is unclear how a relative ratio of the microbiome signature of the candidate animal in the step (b) can be compared to that of a positive reference signature of a single control healthy animal, while the positive reference signature is obtained from a plurality of control healthy animals.
Claim 10 is also indefinite due to recitation of “when a relative ratio of at least 90% of microbes of … the candidate ruminating animal is identical to the relative ratio of microbes of positive … reference signation of said control healthy animal” in the step (b) of the claim. There is no sufficient antecedent basis for the limitation “the relative ratio of microbes of positive … reference signation of said control healthy animal” in the claim. Further, the recited “relative ratio” is a relative term. The claim does not recite any comparison phrase for this relative term. It is unclear which specific parameter’s relative ratio the recited “relative ratio” stands for, and it is unclear based on which specific standard or benchmark the recited “relative ratio” for the candidate and control animals are determined.
Claim 10 is also indefinite due to the recitation of “separating the ruminating animal which is not associated with said milk production phenotype …” in the step (c) of the claim. There is no sufficient antecedent basis for the limitation “the ruminating animal which is not associated with said milk production phenotype” in the claim. The claim does not previously describe any ruminating animal not associated with said milk production phenotype, and there is no comparison step recited in the claim, which leads to the identification of animals not associated with milk production phenotype. Further, It is unclear how a ruminating animal not associated with the milk production phenotype can be identified in the absence of an essential comparison step in the claim.
Claim 11 is indefinite due to recitation of “… rumen microbiome signature … is statistically significantly similar to said negative rumen microbiome reference signature”. It is noted that the term “similar” is a relative term. The limitation “statistically significantly similar” is not defined in the specification. It is unclear at what specific levels of microbe identity (e.g. 10%, 20%, 50%, or 70%), when being compared to microbes of the negative rumen microbiome reference signature, the recited rumen microbiome can be considered as being statistically significantly similar to the negative rumen microbiome reference signature.
The remaining claims are rejected for depending from an indefinite claim.
Claim Rejections - 35 USC § 103
Claims 10-11 and 19-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Zhou et al. (Applied and Environmental Microbiology, 2009, 75(20): 6524-6533, cited in IDS) in view of Baker (US 2013/0052172, 2013 of record), Jami et al. (Anaerobe, 2012, 18: 338-343, cited in IDS), Koike et al. (Asian-Aust. J. Anim. Sci., 2009, 22: 131-138, cited in IDS), Chiquette et al. (J. Dairy Sci., 91: 336-3543, 2008, cited in IDS), and Henn et al. (US 2014/0199281, 2014, effective filing date: Nov. 23, 2012, cited in IDS).
Zhou et al. teach that cattle animals with high feed efficiencies (designated “efficient”) produce less methane gas than those with low feed efficiencies (designated “inefficient”) (abstract/lines 1-2). Zhou et al. disclose a method of analyzing rumen microflora of efficient and inefficient cattle animals, and investigating rumen microbiome signatures associated with feed efficiencies and methane production in rumen of the cattle animals by using culture-independent methods (abstract, pages 6524-6525: Material and Methods), wherein a plurality of healthy cattle animals/steers (n=58) are examined and ranked into a group of efficient cattle animals and a group of inefficient cattle animals (the para spanning pages 6524 and 6525). Zhou et al. demonstrate that methanogenic communities in the remen of inefficient animals are more diverse than those in efficient animals, and specifically, 22 operational taxonomic units (OTUs) are detected in the rumens of efficient animals, compared to 27 OTUs in inefficient animals (abstract, page 6526/table 3, page 6524/para 2/lines 4-5). Zhou et al. further reveal that the prevalence of Methanosphaera stadtmanae and Methanobrevibacter sp. AbM4 is higher in inefficient animals compared to efficient animals (abstract, page 6531/table 4). Overall, Zhou et al. discloses that feed efficiency along with methane production can be determined by analyzing and quantifying methanogenic bacteria of microflora in a rumen of a ruminating animal, wherein the less diverse 22 OTUs along with a lower prevalence of M. stadtmanae and Methanobrevibacter sp. can be considered as a positive rumen microbiome reference signature (based on microbial content of a plurality of healthy efficient animals) for a cattle animal associated with the phenotype of high feed efficiency and low methane production in the remen; whereas, more diverse 27 OTUs along with a higher prevalence of M. stadtmanae and Methanobrevibacter sp. can be considered as a negative rumen microbiome reference signature (based on healthy inefficient animals) for a cattle animal not associated with the phenotype of high feed efficiency.
The method of Zhou et al. differs from the method of claims 10-11 and 19-20 in that Zhou et al. do not teach determining whether a candidate ruminating animal is associated with a phenotype of high feed efficiency by comparing a rumen microbiome signature of the candidate ruminating animal to positive and negative rumen microbiome reference signatures generated by their method, wherein the rumen microbiome signature comprises bacteria belonging to Prevotella, Eubacterium, and/or Lachnospiraceae. However, Zhou et al. teach ruminating cattle animals having high feed efficiency produce 20% to 30% less methane; and methane emission in the livestock industry causes nutritional/energy loss and environmental concerns (page 6524: left col/para 1/last 3 lines, right col/lines 5-7). Thus, there is a need in the art to determine the status of feed efficacy of a candidate ruminating animal in a herd for identifying and separating efficient ruminating animals for the use in the livestock industry.
Baker teaches a method of determining and identifying an individual associated with a particular phenotype (i.e. incidence and/or risk of cardiac defect), comprising: providing a reference microbial signature that correlates with extent or degree of the particular phenotype (i.e. a positive microbiome reference signature obtained from a control individual associated with the phenotype); analyzing microflora in a microbiota sample from an individual(s) and determining a microbial signature of a candidate individual whose particular phenotype is to be identified/determined; and comparing the microbial signature of the candidate individual with the reference microbial signature to determine whether they have statistically significant correlation/association with a p-value of less than 0.05, which is an indication that the candidate individual has the particular phenotype (i.e. the incidence and/or risk of cardiac defect); wherein a microbiota sample comprises microbes in a particular organ or tissue of the individual; wherein the particular organ or tissue of the individual is a gastrointestinal tract; wherein the microbial signature comprises a set of levels of all types of microbes in the microbiota sample; wherein the microbial signature comprises a set of levels of 16S RNA microbial gene abundances of microbiota; and wherein the microbial signature comprises information relating to presence and levels of substantially all types of microbes within a microbiome (claims 1-5 and 8-9, paras. 0035, 0103/last 3 lines, and 0117). Baker further teaches that the individual is an animal including a ruminating animal, such as cow, goat, and sheep; and the microbiota sample is from a gastrointestinal (GI) tract and the microbiome comprise microbes of the GI tract (paras 0092/lines 2-4 from bottom; paras 0093/last 4 lines and 0094/last 2 lines). Given the GI tract of a ruminating animal comprises rumen, it would have been obvious to collect a rumen microbiota sample from a candidate ruminating animal and determining its rumen microbiome signature and comparing it with a positive rumen microbiome reference signature in the method of Baker for determining whether the candidate ruminating animal is associated with the particular phenotype. Baker further teaches that a reference microbial signature is obtained from a healthy individual, i.e. an individual who does not have or have not had the defect, or have no risk factors for developing the defect (para 0132, lines 4-6 and 15-17). As such, Baker teaches comparing to a negative microbiome reference signature based on results from a control healthy animal not associated with the particular phenotype.
Jami et al. teach that the cattle remen houses a complex microbiota, which degrade plant materials, convert them into digestible compounds such as volatile fatty acids and bacterial proteins, then converted into milk; and which determine/define the quality, quantity, and composition of milk, and yields of milk production (abstract: lines 3-5; first page/right col/para 1/lines 3-11). Jami et al. also teach that 32% of rumen bacterial community shared by at least 90% of lactating cows (title, abstract). Jami et al. further analyzed ruminal bacteria of a plurality of healthy lactating cows (n = 16) and compared relative abundance of Prevotella (including P. ruminicola and P. bryantii), Eubacterium (including E. ruminantium), and Lachnospiraceae (e.g. Butyrivibrio and Eubacterium) (see Title, Fig. 4, and the para spanning both cols of page 2).
Koike et al. teach that rumen bacteria are the major microbes in the rumen, and they produce a wide range of highly active plant fiber-degradation enzymes and play a particularly important role in biological degradation of plant fiber/cellulose in the rumen, because of their much larger biomass and higher activity than other microbes (abstract, the paragraph spanning both columns in page 131). Koike et al. also teach that among the major rumen bacteria, the bacteria of species belonging to the genus Prevotella (i.e. P. ruminicola), and the genus Butyrivibrio (i.e. B. fibrisolvens), as well as the genius Eubacterium (i.e. E. cellulosolvens and E. ruminantium) are recognized as fibrolytic bacterial species (page 131, last paragraph) (Note: Butyrivibrio and Eubacterium are genera within the family Lachnospiraceae, thus reading on “Lachnospiraceae” recited in claim 20).
Chiquette et al. teach that Prevotella bryantii (strain 25A) as a probiotic has the benefits of reducing lactate production and an increase in milk fat and ruminal fermentation products in early-lactation dairy cows (title; abstract: left co/lines 3-5 from bottom, right col/lines 3-5 and 12-14; the conclusion spanning pages 3542 and 3543). Chiquette et al. also teach using twelve (six in each group) early-lactation dairy cows for determining the benefits of Prevotella by administering the Prevotella to the early-lactation dairy cows (abstract, the para spanning both cols of page 3537, table 2).
Henn et al. teach bacterial compositions that comprise at least two types of bacteria, may be administered to livestock (e.g., cows) to treat symptoms of diseases, disorders, and conditions associated with a dysbiosis (e.g., inhibit growth, proliferation, and/or colonization of one or a plurality of pathogenic bacteria in the dysbiotic microbial niche, so that a healthy, diverse and protective microbiota colonizes and populates the intestinal lumen in a new host (i.e. a second ruminating animal, e.g. cow) to establish or re-establish control over pathogens). See Henn et al. at [0057]; [0059]; [0062]; and [0131]. The list of bacteria, or bacterial combinations, is taught in Table 1 and includes Lachnospiraceae, Prevotella, Butyrivibrio and Eubacterium (Note: Butyrivibrio are listed as bacteria in the family of Lachnospiraceae). See Henn et al. at [0062]; pgs. 33, 40, 43-44, and 51-54.
At the time the invention was made, it would have been obvious to one of ordinary skill in the art to modify the method of Zhou et al. by further analyzing rumen microflora of a candidate cattle comprised in a herd to determine its rumen microbiome signature, comparing it to the positive rumen microbiome reference signature (based on microbial content of a plurality of control healthy efficient animals) associated with a phenotype of high feed efficiency as well as the negative rumen microbiome reference signature (based on control healthy inefficient animals) associated with low feed efficiency, not associated with high feed efficiency, for determining whether the candidate cattle is associated with the phenotype of high feed efficiency, thus allowing a candidate cattle associated with the phenotype to be identified and separated from the herd in the following step. This is because Zhou et al. demonstrate that all ruminating cattle having high feed efficiency have a microflora with fewer species variation (22 OTUs) and lower prevalence of M. stadtmanae and Methanobrevibacter sp., and on the other hand all ruminating cattle having low feed efficiency have a microflora with more species variation (27 OTUs) and higher prevalence of M. stadtmanae and Methanobrevibacter sp. In addition, it has been well known in the art that a particular phenotype of animals (including ruminating animals) can be determined by comparing microbiome signatures of a candidate ruminating animal to a positive microbiome reference signature associated with the phenotype as well as to a negative microbiome reference signature not associated with the phenotype, as supported by Baker. In addition, the techniques for analyzing rumen microflora for determining rumen microbiome signatures and comparing them to relevant microbiome reference signatures have been well established in the art and they are readily applicable to the modified method of Zhou et al., as supported by Zhou et al. and Barker. Furthermore, Zhou et al. teach that ruminating cattle animals with high feed efficiency have the advantage to be used in the livestock industry, such as producing 20% to 30% less methane, resulting in less nutritional/energy loss, and being more environmentally friendly, when compared to those animals with low feed efficiency.
Regarding the phenotype of milk production recited in the claims 10 and 11, Zhou et al. teach phenotypes of feed efficiencies, but do not expressively teach a milk production phenotype. However, the phenotypes of feed efficiencies of Zhou et al. appears to be interconnected with the claimed milk production phenotype, in view of Zhou et al. teach that ruminating animals with high feed efficiency have less nutrient/energy loss by producing 20-30% less methane, when compared to animals with low feed efficiency, which would allow highly efficient ruminating animals to direct a larger proportion of their energy intake toward synthesizing milk. Accordingly, it would be expected that ruminating animals with a phenotype of high feed efficiency in the method suggested by Zhou et al. and Barker have a phenotype of high milk production or good milk quality, while ruminating animals with a phenotype of low feed efficiency have a phenotype of poor milk production.
Regarding the limitations about comparing a relative ratio of microbes in the microbiome signature of a candidate animal to that of positive microbiome reference signature for determining whether the candidate animal is associated with a phenotype of milk production (quality and/or quantity) as recited in the claims 10 and 19-20, it would have been obvious to further compare a relative abundance of bacteria belonging to the genus Prevotella, the genus Eubacterium, and the family Lachnospiraceae (e.g. the genus Butyrivibrio) in the microbiome signature of a candidate ruminating cattle to that of positive microbiome reference signatures in the method suggested by Zhou et al. and Baker for determining whether the candidate cattle is associated with phenotypes of high feed efficiency and milk production, because it is well known in the art that Prevotella (e.g. P. ruminicola, P. bryantii), Eubacterium, and Lachnospiraceae (e.g. Butyrivibrio) are major rumen fibrolytic bacteria, and their presence contributes to degradation of plant fibers of feeds and their conversion to milk by enhancing feed fermentation/utilization as well as improving milk production/quality, as supported by Koike et al., Jami et al., and Chiquette et al.; and these bacteria provide additional benefits of improving health of ruminating animals, as supported by Henn et al. Furthermore, techniques for analyzing and comparing a relative ratio of Prevotella, Eubacterium, and Lachnospiraceae have been well established in the art and readily applicable to the modified method of Zhou et al., as supported by Jami et al. Moreover, it is noted that the benefits of Prevotella, Eubacterium, and Lachnospiraceae, as taught by Koike et al. and Henn et al., facilitate the establishment of a healthy, diverse and protective microbiota in the rumen of cattle animals (e.g. dairy cows), which improves fiber digestion/feed utilization and inhibits pathogenic bacterial infection. This in turn improves phenotypes of growth, milk quantity and/or quality, and yields of milk production in ruminating animals, in view of the fact that sick and unhealthy animals with low feed efficiencies grow poorly, which would be expected to have low milk production with poor quality/quantity.
Regarding the limitation about at least 90% of microbes of a rumen microbiome signature of a candidate animal have a relative ratio identical that of a control animal as recited in the claim 10, Zhou et al. do not specifically teach an identical percentage. However, Jami et al. teach that at least 90% of lactating cows share 32% of rumen bacterial community, indicating similar/identical microbes with a relative ratio can be identified in the rumen; Zhou et al. teach that all ruminating cattle with high feed-efficiency phenotype have a lower prevalence of M. stadtmanae and Methanobrevibacter sp., and on the other hand all ruminating cattle with low feed efficiency phenotype have a higher prevalence of M. stadtmanae and Methanobrevibacter sp.; and the lower prevalence of M. stadtmanae and Methanobrevibacter sp. is considered as a positive rumen microbiome reference signature for a cattle associated with the high feed efficiency phenotype, as indicated above. Furthermore, Koike et al., Jami et al., Henn et al., and Chiquette et al. teach that the presence of remen bacteria of Prevotella, Eubacterium, and Lachnospiraceae contributes to enhanced degradation of plant fibers/feeds for effective feed utilization in the rumen, improved milk production, as well as improved health of ruminating animals. As such, it would have been obvious to one of ordinary skill in the art when a relative prevalence/ratio of 100% of microbes of M. stadtmanae, Methanobrevibacter sp., Prevotella, Eubacterium, and Lachnospiraceae (as rumen microbiome signature) of a candidate cattle is identical to that of a positive rumen microbiome reference signature of a control cattle, it is an indication that the candidate cattle has high feed-efficiency phenotype along with milk production phenotype.
Regarding the step (c) in the claim 10, it would have been obvious to separate the candidate cattle associated with high feed efficiency phenotype along with milk production phenotype into a separate herd in the method suggested by the cited prior art, because these phenotypes are desirable feature for cattle animals in the livestock industry.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was made.
Claims 10-11 and 19-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Jami-2 et al. (PLOS ONE, 9 (1) e85423, pages 1-6, published in January 2014, cited in IDS) in view of Baker (US 2013/0052172, 2013, of record).
Jami-2 et al. analyzed rumen microflora in a plurality of healthy dairy cows (n = 15), compared relative abundance of rumen bacteria, and generated/identified rumen microbiome reference signatures associated with milk production phenotype such as milk yield and milk composition (title, abstract). Specifically, the rumen microbiome reference signatures associated with milk production phenotype include a ratio of the phyla Firmicutes to Bacteroidetes, which has strong correlation with milk-fat yield (see abstract), wherein the analysis of relative abundance of the genera from the phyla Firmicutes reveals that 5 of them are positively correlated with milk-fat yield and they belong to the genus Eubacterium and the family Lachnospiraceae (page 3/last 7 lines, Fig. 4) (Note: these are a positive rumen microbiome reference signature associated with the milk production phenotype of milk-fat yield); and wherein analysis of relative abundance of the genera from the phyla Bacteroidetes reveals that the genus Prevotella is the most abundant genus in the rumen and it has a negative correlation with milk-fat yield (page 3/left col: in the middle of last para; Figs 3-4) (Note: the genus Prevotella is a negative rumen microbiome reference signature associated with the milk production phenotype of milk-fat yield).
The method of Jami-2 et al. differs from the claimed method in that Jami et al. do not teach determining whether a candidate ruminating animal is associated with a phenotype of milk production by comparing a rumen microbiome signature of the candidate ruminating animal to the positive and negative rumen microbiome reference signatures generated by their method.
The teachings of Baker are described above.
At the time the invention was made, it would have been obvious to one of ordinary skill in the art to modify the method of Jami-2 et al. by further analyzing rumen microflora of a candidate dairy cow comprised in a herd to determine its rumen microbiome signature and comparing it to the positive rumen microbiome reference signature (obtained from a plurality of healthy control dairy cows) associated with the phenotype of milk production as well as the negative rumen microbiome reference signature (of a healthy control dairy cow) not associated with phenotype of milk production for determining whether the candidate dairy cow is associated with a phenotype of milk production, e.g. milk-fat yield. This is because Jami-2 et al. demonstrate that dairy cows having the positive rumen microbiome reference signature are associated with the phenotype of milk production, and dairy cows having the negative rumen microbiome reference signature are not associated with the phenotype of milk production. In addition, it is well known in the art that a particular phenotype of animals (including ruminating animals) can be determined by comparing their microbiome signatures to a positive microbiome reference signature associated with the phenotype as well as to a negative microbiome reference signature not associated with the phenotype, as supported by Baker. Furthermore, the techniques for analyzing rumen microflora for determining rumen microbiome signatures and comparing their relative abundances to relevant microbiome reference signatures have been well established in the art and they are readily applicable to the modified method of Jami-2 et al., as supported by Jami-2 et al. and Barker. With regard to the limitation “at least 90% of microbes … of the candidate ruminating animal … identical to … microbes … of said control healthy animal” recited in the claim 10, the positive reference signature of Jami-2 et al. have 5 genera. It would have been obvious for the signature of the candidate cow to have microbes in all these 5 genera (i.e. 100% identity) of the positive reference signature of Jami-2 et al. in the modified method of Jami-2 et al. for accurately determining whether a candidate cow to be associated with the milk production phenotype, e.g. milk-fat yield.
Regarding the claims 19 and 20, Jami-2 et al. teach comparing relative abundance of Prevotella, Eubacterium, and Lachnospiraceae, as indicated above.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant's arguments about the claim objection in the response filed on 03/16/2026 (page 5) have been fully considered, but they are moot because the objection has been withdrawn, as indicated above. The newly amended claims are objected because they raise new issues (see details above).
Applicant's arguments about the rejection under 35 U.S.C. 112(b) in the response filed on 03/16/2026 (page 5) have been fully considered, but they are only persuasive in part, because Applicant did not address the issue about the relative term of “relative ratio” recited in the claim 10. Applicant is reminded of 37 C.F.R. 1.111, requiring a complete reply to every ground of objection and rejection in the prior office action. This rejection is maintained.
Applicant's arguments about the rejection of claims 10-11 and 19-20 under 35 U.S.C. 101 in the 03/16/2026 response (page 5) have been fully considered, but they are moot because the rejection has been withdrawn, as indicated above.
Applicant’s arguments about the rejection of Claims 10-11 and 19-20 under 35 U.S.C. 103(a) over Zhou in view of Baker, Koike, Henn and Jami in the 03/16/2026 response (pages 6-7) have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s arguments based on the limitation “a plurality of control healthy animals …” newly added to the claim 10 in pages 6-7 of the response, it is a common practice in the art to use a plurality of animals as a control or assay group for reducing individual variations among animals, as evidenced by Zhou, who divided 58 steers into a group comprising a plurality of (control) healthy animals having high feed efficiency and a group comprising a plurality of (control) healthy animals having low feed efficiency; as evidenced by Chiquette, who teaches analyzing six (a plurality of) healthy dairy cows in each of control and treatment groups for determining the effect of Prevotella on milk production phenotypes; as evidenced by Jami, who teaches analyzing ruminal bacteria in a group comprising 16 (a plurality of) healthy lactating cows; as evidenced by Jami-2, who teaches analyzing rumen microflora in a group comprising 15 (a plurality of) healthy dairy cows; and as evidenced by Mayer (PLOS One, doc. no. 0129174, 17pp., 2015, cited in newly filed IDS), who teaches determining the feed efficiency of ruminant animals by measuring the presence of different rumen bacteria in ruminant animals of groups 1 and 2, which respectively comprise 148 healthy animals and 197 healthy animals (abstract, the para spanning pages 2 and 3).
Given Zhou expressively teaches that the positive rumen reference microflora of high feed efficiency is based on microbial contents of a plurality of healthy ruminating animals, it would have been obvious to use a positive rumen reference microbiome signature based on microbial contents of a plurality of control healthy ruminating animals for the comparison with microbiome signature of a candidate animal in the method suggested by Zhou, Baker and other cited prior art.
With regard to Applicant’s arguments in page 6/para 4 – page 7/para 1 of the response, they are not persuasive because Applicant failed to provide any factual evidence to support the argument that “Feed efficiency is a digestion-related metabolic trait and is unrelated to the milk production phenotype recited in the present claims”. There are no teachings in the prior art or the specification of the instant application to support that a rumen microbiome signature associated with a phenotype of high feed efficiency is distinct from a rumen microbiome signature associated with a phenotype of high milk production or quality. Although Zhou does not expressively teach a phenotype of milk production, this phenotype is considered to be interconnected with the feed efficiency milk phenotype taught by Zhou, and the claimed phenotype of milk production would have been obvious over Zhou and other cited prior art for the reasons indicated above.
In response to applicant's arguments against the secondary references (Baker, Jami, Koike, and Henn) individually in page 7 of the response, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Overall, the claimed invention for selecting candidate animals associated with a milk production phenotype would have been obvious over the combined teachings of Zhou, Baker, Koike, Henn, Jami and Chiquette; and the conclusion of the obviousness of the newly amended claims 10-11 and 19-20 has been established for all the reasons indicated above.
Applicant’s arguments about the rejection of Claims 10-11 and 19-20 under 35 U.S.C. 103(a) over Jami-2 in view of Baker in the 03/16/2026 response (page 8) have been fully considered but they are not persuasive for the following reasons.
First, Applicant’s arguments based on substantial variability with ~50% of optional taxonomic units occurred in only 0-30% of animals sampled are not relevant to the teachings of Jami-2. It appears that Applicant referred to an incorrect reference. In addition, these arguments are based on the features not recited in the claims, because the instant claims do not recite any limitations to define microbial variability in the microbiome reference signatures. Furthermore, in contrary to Applicant’s arguments, Jami-2 expressively teaches generating rumen microbiome reference signature from a plurality of healthy control animals, n =15 (see abstract/lines 3-4 and page 2/left col/lines 8-9); and expressively teaches there is an association with a phenotype of milk production, see abstract “We … found that some physiological parameters, such as milk yield and composition, are highly correlated with the abundance of various bacterial members of the rumen microbiome” (emphasis added). As such, Jami-2 meets the claimed limitations.
Second, Applicant’s arguments about Baker in page 8 of the response are not persuasive. It is noted that Baker teaches reference microbial signature can be derived from multiple healthy control animals, see para 0117/right col/lines 1-7, wherein a plural form “individuals” is used for identifying, defining, or classifying microbiomes associated with a phenotype. Furthermore, the primary reference Jami-2 expressively teaches generating rumen microflora derived from a plurality of healthy control animals. As such, the claimed invention of using a reference signature derived from a plurality of control healthy animals has no novelty in view of Jami-2 and Baker.
Overall, the conclusion of the obviousness of the newly amended claims 10-11 and 19-20 has been established for all the reasons indicated above.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Qing Xu, Ph.D., whose telephone number is (571) 272-3076. The examiner can normally be reached on Monday-Friday from 9:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached at (571) 272-0939. Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to the receptionist whose telephone number is (571) 272-1600
/Qing Xu/
Patent Examiner
Art Unit 1656
Prosecution Insights