DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
The present application remains examined under applicant’s election of Group I and the election of “a microbial composition consisting of microbes of the species Akkermansia muciniphila” as the specific composition.
Claims 2-6, 11, 13-14, 17, and 20 are directed to the elected invention and have been examined pursuant to the species election.
Claims 21-24 are directed to the non-elected invention and remain withdrawn.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/18/2026 is in compliance with the provisions of 37 C.F.R. 1.97. All references cited in this IDS have been fully considered.
Amendments
Claims 2-3 now limit the commercially desirable phenotype to increase in fertility, a decrease in methane production, an increase in milk production, an increase in milk quality, an increase in meat quality, and an increase in feed efficiency.
Claim 6 has had a minor typographic change.
Claim 11 now depends from claim 2 and has had a minor typographic change.
Claim 17 has changed “agent” to composition which alters the amount of the genus Akkermansia in the microbiome of the newborn.
Drawings
Previous objection to the drawings
The drawings were objected to because they contained subject matter which is not easily distinguished based on the currently presented shading. Applicant asserts that a petition for colored drawings was filed. Applicant’s petition was dismissed on 10/17/2025 because the specification lacked a statement of color drawings. On 12/17/2025, applicant amended the specification to contain the statement of color drawings. The petition is currently pending. Because the petition has not been acted upon, the objection must be maintained.
Maintained objection to the drawings
The drawings are objected to because figures 1B, 2A-2E, and 3A-3B contain subject matter which is not easily distinguished based upon the currently presented shading. Although it is acknowledged that applicant has filed a petition for colored drawings, the petition has not yet been accepted. Accordingly, as presented, the drawings in black and white have improper shading.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered, and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Previous objections to the claims
Claims 11 and 17 were objected to for minor informalities. Applicant has made the appropriate amendment; thus, the objections are withdrawn.
New objections to the claims
Claim 17 is objected to because the genus Akkermansia should be italicized in line 3.
Claim 17 is further objected to because the word “comosition" in line 3 is an apparent misspelling of “composition”.
Appropriate correction is required.
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.
Previous rejection under 35 U.S.C. § 112(b)
RE: Rejection of claims 6 and 17 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claims 6 and 17 were rejected for lack of antecedent basis. Applicant has made the appropriate amendments to claims 6 and 17 and the claims are no longer considered to be indefinite. Therefore, the rejection under 35 U.S.C. § 112(b) is withdrawn.
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.
Previous rejection under 35 U.S.C. § 103
RE: Rejection of claims 2-6, 9-10, 13-14, 17, and 20 under 35 U.S.C. 103 as being unpatentable over Lynch et al. (WO 2017/152137 A2; cited previously) in view of Diao et al. (Animals, 2019, Vol. 9(490), pages 1-15).
Applicant traverses the rejection of record by arguing that the claimed invention requires manipulation of a particular bacterial species (A. muciniphila) and while Lynch discloses numerous bacterial species including A. muciniphila, the species is presented as part of a broad consortia intended for treating diseases such as dysbiosis or inflammation and there is no teaching or motivation to specifically select A. muciniphila out of all of the numerous bacterial species as a target for manipulation.
Applicant supports this argument by citing data which show that A. muciniphila is naturally enriched during newborn stage and declines sharply thereafter, making this stage “uniquely suited” for targeted microbiome engineering (Remarks, p. 6, par. 4). And Lynch merely mentions neonates among a laundry list of possible subjects but does not assign any particular significance or necessity to this developmental stage. In contrast, applicant’s invention allegedly leverages a “narrow and critical temporal window” that is not taught or suggested by the prior art references. Specifically, applicant asserts that their invention “uniquely identifies and exploits the concept of priority effects in microbiomes succession” which is a technical advantage absent from Lynch and Diao (Remarks, p. 6, par. 4).
Finally, applicant asserts that the claimed methods have been limited to improving long-term commercially desirable phenotypes and the cited references do not recognize A. muciniphila as a keystone species nor identify the newborn period as a critical window for effective colonization.
Applicant’s arguments have been fully considered but are not sufficient to overcome the rejection of record for the following reasons.
First, although it is acknowledged that Lynch teaches a litany of bacterial genera and species which are useful for the invention, it nonetheless teaches methods of using a composition consisting of 1 bacterial species selected from a list which comprises Akkermansia muciniphila ([0006]-[0007]). Thus, it teaches administration of a composition consisting of Akkermansia muciniphila. A reference that clearly names the claimed species anticipates the claim no matter how many other species are named (MPEP § 2131.02(II)). Thus, Lynch’s disclosure of the usefulness of this species on its own is sufficient to provide teaching or motivation to specifically select A. muciniphila.
Second, although it is appreciated that applicant’s invention is temporally limited (“at the newborn stage of life”), as discussed in the rejection of record, Lynch teaches administration to a ruminant at the newborn stage of life ([0174]) and Diao teaches the importance of establishing a rumen microbiota in the post-birth period because it is crucial to the growth and milk production. As such, it would have been obvious to have used the composition taught by Lynch during the time period taught by Diao in order to boost a commercially desirable phenotype.
Third, as discussed above, Diao discloses the newborn stage as being crucial for growth and milk production and Lynch teaches administration during this stage of life. And although neither Lynch nor Diao directly teach that A. muciniphila is useful for boosting the particular phenotypes recited in the claim, as discussed in the rejection of record, Ogola et al. and Bobbo et al. teach that inflammation is inversely related to milk production and therefore using Lynch’s composition which treats or prevents inflammation ([0009]) would have been expected to result in at least improvement of milk production.
For at least these reasons, the rejection of record must be maintained. In order to be fully responsive to applicant’s amendments, the rejection is withdrawn and a new ground of rejection is made below.
New ground of rejection under 35 U.S.C. § 103
Claims 2-6, 11, 13-14, 17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Lynch et al. (WO 2017/152137 A2; cited previously) in view of Diao et al. (Animals, 2019, Vol. 9(490), pages 1-15), Ogola et al. (Journal of Veterinary Science, 2007, Vol. 8(3), pages 237-242) and Bobbo et al. (Journal of Dairy Science, 2017, Vol. 100(6), pages 4868-4883).
Lynch et al. (hereinafter Lynch) teaches methods and microbial compositions including Lactobacillus johnsonii, Faecalibacterium prausnitzii, Akkermansia muciniphila, Myxococcus xanthus, and Pediococcus pentosaceus which are “surprisingly useful for the treatment of dysbiosis, infections, and inflammatory disease” ([0005]). Lynch teaches that the methods and compositions comprising a bacterial population can comprise, consist essentially of, or consist of 1-8 bacterial species ([0006]). In embodiments, the bacterium is Akkermansia sp., specifically Akkermansia muciniphila (([0007]-[0008]).
Regarding claim 2, Lynch teaches methods for administering to a “subject” an effective amount of “one or more of the agents provided herein” and the amount is the amount necessary to produce a desired physiologic response such as a reduction of inflammation, infection, or dysbiosis ([0147]).
With respect to this method being performed in a ruminant, Lynch teaches that the subject may be a living member of the animal kingdom, which is suffering from, or which may suffer from the indicated disorder and in some embodiments this subject is a mammal including livestock such as pigs, bovines, donkeys, mules, bison, goats, camels, sheep, and deer ([0082]). Cows (bovines), sheep, goats, and deer are ruminants.
With respect to the composition being administered to the ruminant when it is at the newborn stage of life, Lynch teaches that in some embodiments, the subject is a neonate or is less than about 1-12, 18, or 24 months old ([0174]). As such, Lynch teaches embodiments wherein the ruminant is at the newborn stage of life.
With respect to the composition being a microbial composition consisting of microbes of the species Akkermansia muciniphila (elected species), Lynch’s microbial composition can consist of Akkermansia muciniphila (“the microbial compositions provided herein may include a bacterial population that…consists of any 1, 2, 3, 4, 5, 6, 7, or 8 of….Akkermansia sp.”; [“[i]n some embodiments, a microbial composition comprises one or more bacterial cells of the bacterial type….Akkermansia muciniphila”; [0138]).
With respect to the composition being a composition which alters the amount of the genus Akkermansia in the microbiome of the newborn ruminant, as Lynch teaches that the Akkermansia bacterial population is administered to the subject, the composition is considered to inherently possess the ability to alter the amount of the genus Akkermansia in the microbiome of the newborn ruminant. This determination is supported by the fact that the only administered bacterial species is the species which is altered and there is no particular limitation on the extent of the alteration (e.g., any increase or reduction of Akkermansia muciniphila is sufficient to meet the limitation “alter the amount of the genus Akkermansia”).
Thus, Lynch teaches a method for a ruminant animal comprising administering to the ruminant a composition which alters the amount of the genus Akkermansia in the rumen microbiome, wherein said composition consists of Akkermansia muciniphila.
Lynch differs because it does not teach that the method is for improving a commercially desirable phenotype wherein the commercially desirable phenotype is selected from the group consisting of an increase in fertility, a decrease in methane production, an increase in milk production, an increase in milk quality, an increase in meat quality, and an increase in feed efficiency.
Nonetheless, Ogola et al. (hereinafter Ogola) teaches that small-scale dairy farms sometimes show sub-optimal animal performance which could be attributed to poor management and disease (p. 237, left col., par. 1). Mastitis, particularly subclinical type, is one of the most persistent and widely spread disease conditions of importance to milk hygiene among dairy cattle (p. 237, right col., par. 1). Mastitis influences the total milk output and modifies milk compositions (Id.). In cows, somatic cell count (SCC) is a predictor of subclinical mastitis and elevated SCC is associated with altered protein quality, change in fatty acid composition, lactose, ion and mineral concentration, increased enzymatic activity, and a higher pH of raw milk (Id.). Ogola teaches that cows with elevated subclinical mastitis (as measured by SCC) have an inversely and significantly decreased lactose content in their milk (p. 239, Table 1). Ogola further teaches that high SCC content is associated with infection status and due to the high prevalence rate of infection in small scale dairy herds, most quarters classified as uninfected are likely to have been subjected to several previous infections (p. 241, left col., par. 2).
Bobbo et al. (hereinafter Bobbo) reinforces Ogola by teaching that bovine mastitis is an inflammatory response of the mammary gland to infection and is well known to decrease milk yield and quality (p. 4868, right col., par. 1). Clinical and subclinical mastitis is characterized by an increase in milk SCC (p. 4868, right col., par. 1 through p. 4869, left col., par. 1) and higher SCC is associated with reduction in milk lactose content (p. 4869, left col., par. 1; p. 4876, Table 5).
Accordingly, because Lynch teaches Akkermansia muciniphila as being surprisingly useful for the treatment of infection and inflammation and because both Ogola and Bobbo teach that mastitis (i.e., infection-related inflammation) results in reduced milk production and has been linked with high SCC, leading to altered protein quality, changes in fatty acid composition, lactose, ion and mineral concentration, increased enzymatic activity, and a higher pH of raw milk (i.e., sub-optimal milk quality), it would have been obvious to have modified Lynch’s method such that the modified method is directed to improving the commercially desirable phenotype of milk production and/or milk quality. There would have been a reasonable expectation of success because Lynch teaches the composition as being anti-inflammatory, which is linked to milk production and worsened milk quality by Ogola and Bobbo. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
The claims further differ because neither Lynch, Ogola, nor Bobbo teach that the method is for improving a commercially desirable phenotype of an adult ruminant, Lynch does not specifically teach that the effect is carried forward into adulthood when administered to a newborn ruminant (i.e., that the composition is administered to a newborn to elicit an effect in an adult).
Nonetheless, Diao et al. (hereinafter Diao) teaches that rearing healthy calves is very important as it can have a significant impact on their growth and milk production performance in adult life (p. 1, par. 1). Adequate calf development is therefore crucially important for the entire dairy industry as calves are challenged by a series of stress factors after they are born (Id.). Specifically, these changes in environmental factors includes a departure from the sterile uterus to natural outside conditions and changes in nutrition (p. 1, par. 1 through p. 2, par. 1). Due to poor immunity and the incomplete development of the digestive system in young calves, any interference from the external environment or changes to the nutrition can drastically affect the development of calves (p. 2, par. 1). At birth, the rumen is not completely developed and significant changes in rumen development have to occur including the establishment of rumen microbiota (p. 2, par. 2).
Accordingly, although Lynch does not directly teach that the method of improving a commercially desirable phenotype of a ruminant is for improving the phenotype in an adult ruminant by administering to the ruminant when it is at the newborn stage of life, because Diao teaches that rearing healthy calves is crucial to the growth and milk production in adult life and because Diao teaches that the post-birth period encompasses significant changes such as the establishment of rumen microbiota, it would have been obvious to have further modified the method of Lynch in view of Ogola and Bobbo such that the newborn ruminant is administered the composition in order to elicit the improvement of a commercially desirable phenotype of an adult. There would have been a reasonable expectation of success because Diao demonstrates that the newborn stage is the stage at which bacterial colonization typically occurs and therefore the probiotic would have been expected to establish the A. muciniphila colonization through adulthood. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Accordingly, claim 2 is obvious over Lynch in view of Ogola, Bobbo, and Diao.
Regarding claim 3, as discussed above, Lynch in view of Ogola, Bobbo, and Diao makes obvious a method of improving a commercially desirable phenotype of an adult ruminant by administering A. muciniphila (i.e., the agent) to a ruminant at a newborn stage of life.
For the reasons discussed above, it would have been obvious to have “selected” A. muciniphila as the agent because Lynch in view of Ogola, Bobbo, and Diao makes obvious improving a commercially desirable phenotype of an adult ruminant by administering A. muciniphila to a newborn ruminant.
Thus, the instant method differs only by further performing a step of analyzing the desirable phenotype in the ruminant at the adult stage of life, when an improvement of said desirable phenotype is indicative that said agent has a positive effect on said desirable phenotype.
It would have been obvious to have made such an observation because Lynch teaches that the effects of administered compositions may be determined empirically ([0147]). Thus, a person having ordinary skill in the art would have readily recognized that they could analyze the desirable phenotype in the adult stage of life. There would have been a reasonable expectation of success because Lynch in view of Diao already makes obvious that the “agent” (A. muciniphila) would be capable of improving a commercially desirable phenotype of an adult ruminant. And therefore, the additional “analyzing” step merely replicates the findings of Lynch in view of Diao.
Regarding claim 4, as discussed above, Lynch in view of Ogola, Bobbo, and Diao makes obvious the method wherein the agent is a microbial composition consisting of microbes of the species Akkermansia muciniphila.
Regarding claim 5, as discussed above, Lynch teaches the administration to a neonate which is less than about 1 month old ([0174]). Accordingly, Lynch teaches an age range (0 to 1 month) which entirely encompasses applicant’s range of younger than 15 days (i.e., 0 to 14 days). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP § 2144.05(I)). There is no evidence that administration in this age range is critical or elicits an unexpected or remarkable result.
Regarding claim 6, as discussed above, Lynch in view of Ogola, Bobbo, and Diao makes obvious the method wherein the bacteria is a microbial composition consisting of microbes of the species Akkermansia muciniphila.
Regarding claim 11, as discussed above, Lynch in view of Ogola, Bobbo, and Diao makes obvious imparting a commercially desirable phenotype such as improving milk quality. Specifically, as discussed above, Ogola teaches that mastitis is associated with altered protein quality (i.e., protein content), changes in fatty acid composition (i.e., fat content), and lactose content.
Regarding claim 13, Lynch teaches that the administration can be single or multiple (i.e., wherein said administering is effected more than one time)([0153]).
Regarding claim 14, Lynch teaches that the composition may be administered to the gastrointestinal tract by enema (i.e., that said composition is comprised in an enema)([0151]).
Regarding claim 17, Lynch teaches that in embodiments, the subject is a subject who has been administered an antibiotic within the last 1-4 months ([0173]). As such, Lynch teaches the method further comprising administering to the newborn ruminant an antibiotic prior to the administration of the composition which alters the amount of the genus Akkermansia in the microbiome of the newborn.
Regarding claim 20, as discussed above, Lynch teaches the methods involving the administration to a neonate which is less than about 1 month old ([0174]). Accordingly, Lynch’s neonate subjects are necessarily not weaned.
Even if Lynch’s subjects are not considered to be pre-weaning subjects, Diao teaches that weaning age can influence the development of rumen in pre-ruminants and teaches weaning calves at 6 and 9 weeks of age (p. 8, par. 2). Accordingly, Diao demonstrates that ruminants “less than about 1 month old” are not weaned.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/GRANT C CURRENS/Examiner, Art Unit 1651