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 .
Claim Objections
Claims 1 and 27 are objected to because of the following informalities:
Regarding claim 1, in line 5 insert “the” before “non-digestible” to place the claim in better form. It is noted the term was present in the previous claims filed 9/8/2025, and it appears removal of the term from the claim was unintentional.
Regarding claim 27, in lines 2 and 4 delete “and” after “oligosaccharides” and insert “,”.
In lines 2 and 5, insert “,” after “infantis”.
Appropriate correction is required.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 7-8, 22, 25 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Nutricia (WO 2017/043962 A1) in view of Wiklund (US 6,333,055 B1) and Buck et al. (US 8,802,650 A1). McCoy (US 5,116,737 A) is relied on as evidence for claims 25 and 27.
Regarding claim 1, Nutricia teaches a nutritional composition comprising digestible carbohydrates (page 11 line 33 to page 12 line 3), protein (page 11 lines 13-17), lipid (page 12 lines 4-5), and prebiotics (non-digestible oligosaccharides) selected from the group consisting of galacto-oligosaccharides and fructo-oligosaccharides (page 9 lines 7-9). The prebiotics are present in an amount of 0.05-20 wt% of the composition (page 9 lines 30-33). Nutricia further teaches the composition comprises B. longum spp infantis and B. breve (page 5 lines 24-25).
Regarding the nutritional composition being “an infant formula, a follow-on formula or a young child formula”, the limitation is interpreted in view of the specification to include ages up to 36 months (page 11 lines 23-32). Nutricia teaches the composition can be infant formula (column 11 lines 8-11).
Nutricia does not specify the prebiotics are present in an amount of 0.2-2 g per 100 ml.
However, the reference teaches the prebiotics are present in therapeutically effective amounts (page 9 line 30), and the overall content of the prebiotics within the composition can vary based on the type/application (page 10 lines 5-8). A supplement comprising 80 wt% of prebiotics in the total composition would have a concentration greater than a nutritional product comprising 20 wt% prebiotics. The reference further teaches that oligosaccharides stimulate growth of bifidobacterial and Lactobacilli, which confer benefits to the host wellbeing and health (page 8 lines 24-30).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the formula of Nutricia to comprise the claimed concentration of oligosaccharides since the reference already teaches varying oligosaccharide content, since the evidence of record does not indicate criticality or unexpected results associated with the feature, and since the values would have been used during the course of routine experimentation and optimization procedures due to factors such as therapeutic amount, stimulation of bifidobacterial and Lactobacilli, flavor, texture/mouthfeel, nutritional profile, characteristics of the consumer e.g., weight, age, size, sex, and volume of the composition e.g., a concentrated supplement or a composition diluted in water or milk.
Nutricia does not teach urea present in an amount of 15-75 mg per 100 ml.
Wiklund teaches urea as an additive to infant formula for prophylaxis of SIDS (abstract), the formula comprising varying amounts of urea based on age (column 4 line 64 to column 5 line 3; column 6 to column 7 examples 1-3). For example 1, the composition comprises 120 mg urea in about 1.2 L, which is about 10 mg per 100 ml. The amount is about 25 mg per 100 ml for example 2, and about 23 mg per 100 ml for example 3.
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the formula of Nutricia to include 15-75 mg per 100 ml urea since the prior art already acknowledges adding an amount of urea in the claimed range to infant formula, and therefore to similarly provide a sufficient amount for prophylaxis of SIDS, and since the claimed values would have been used during the course of routine experimentation and optimization procedures due to factors such as desired prophylactic effect, volume and type of the composition, and characteristics of the intended user e.g., weight, age, sex, etc.
Nutricia does not teach the composition further comprises 2’-fucosyllactose (2’FL).
Buck et al. teaches formulas comprising human milk oligosaccharides (HMO) that can reduce inflammation and thereby improve airway defense mechanisms and overall airway respiratory health in an infant, toddler or child (column 1 lines 16-23), where the HMO includes 2’FL (column 2 lines 20-21).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the composition of Nutricia to include 2’FL since the prior art acknowledges the substance can be included in nutritional formulas for infants, and therefore to provide the same advantages taught by Buck et al.
Regarding claim 7, Nutricia teaches the composition comprises no more than 2 g protein per 100 kcal (page 11 lines 13-14).
Regarding claim 8, the claim is interpreted to recite alternatives, separated by the term “or”. For the sake of examination, the alternative “cow milk proteins” is chosen. Nutricia teaches the composition comprises cow milk proteins, which are considered to provide the minimum requirements for essential amino acid content for satisfactory growth (page 11 lines 18-22).
The reference does not teach the composition comprising at least 90 wt% cow milk proteins based on total protein.
However, it would have been obvious to one of ordinary skill in the art at the time of the invention to modify the composition of Nutricia to have the claimed weight percentage based on total protein since the reference already teaches cow milk proteins are preferred, since there is no evidence of criticality or unexpected results associated with the claimed feature, and since the claimed values would have been used during the course of routine experimentation and optimization procedures due to factors such as amino acid profile and minimum protein requirements for satisfactory growth.
Regarding claim 22, the combination applied to claim 1 does not teach 1.13-5.6 wt% urea based on total protein in the composition.
Nutricia further teaches adjusting the amount of protein based on desired fraction of total calories and minimum requirements for essential amino acid for growth (page 11 lines 15-19), where the formula can comprise at least 3 wt% casein based on dry weight.
With respect to urea content of the combination, Wiklund further teaches the urea can be added in varying amounts to obtain concentrations of 1-5 mmol/L for an infant during the first month of life (column 5 lines 19-22), and 1-10 mmol/L for a child during months 2-7 of life (column 5 lines 27-29).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the formula of Nutricia to include urea in the claimed weight percentage based on total protein in the composition since the reference acknowledges adjusting protein content, and Wiklund teaches adjusting urea concentration, where the urea concentration is increased based on age, and therefore since the claimed values would have been used during the course of routine experimentation and optimization procedures due to factors such as requirements for growth, age, and prophylaxis of SIDS.
Regarding claim 25, Nutricia teaches a nutritional composition comprising urea and non-digestible oligosaccharides in the respective amounts, as well as the claimed Bifidobacteria. The composition comprising 2’ fucosyllactose is obvious in view of the combination applied to claim 1. The combination does not teach that the two components “synergistically stimulate growth of intestinal Bifidobacteria”.
Applicant’s specification states that “a symbiotic, improved or synergistic effect is to be expected from urea together with non-digestible oligosaccharides”, where this effect is achieved by urease-positive Bifidobacteria that “will beneficially affect the growth of other Bifidobacterium strains that are urease negative, by producing the growth factor CO2 and by releasing ammonium as nitrogen source. This released CO2 and ammonia can then be used by urease negative Bifidobacteria resulting in a more diverse and further improved microbiota.” (page 19 lines 5-12). The limitation in question is interpreted in view of the cited disclosure.
Nutricia teaches non-digestible oligosaccharides are fermented by intestinal microbiota of the infant, thereby stimulating growth of Bifidobacteria and Lactobacilli, and in turn stimulating healthy intestinal microbiota (page 8 lines 24-30). The reference further teaches bifidobacterial colonization of gut of C-section infants is desirable, and colonization of at least one Bifidobacterium species promotes intestinal colonization of other species (page 6 line 31 to page 7 line 6). It is further desirable to improve and/or accelerate developing the appropriate bifidobacterial population and Bifidobacterium species in infants, where improving gastrointestinal Bifidobacterium population and diversity of species provides multiple health benefits (page 4 lines 12-28). Thus, the reference suggests that colonization of the gut with at least one urease-positive Bifidobacterium species would facilitate proliferation and colonization of other urease-negative bacterium naturally present within the gut. It is noted that the motivation for incorporating urea into the composition of Nutricia is to provide prophylaxis of SIDS as stated for claim 1.
McCoy teaches a method for growing urease-producing (urea metabolizing) bacteria in a medium containing urea, the urease-producing bacteria including Bifidobacterium, where ammonia and carbon dioxide produced by hydrolysis of urea neutralizes the acid produced in the culturing, thereby allowing for a higher pH to be maintained to facilitate “rapid bacterial culture and high bacteria activity” (column 3 lines 12-27). The ammonia produced by urea hydrolysis limits pH drop in the growth medium and facilitates maintaining the pH in a range that promotes growth of the bacteria (column 3 lines 49-53). The reference shows that the process disclosed by Applicant, with respect to hydrolysis of urea into ammonium and carbon dioxide to facilitate Bifidobacterium growth, is expected by the prior art.
The combination applied to claim 1 teaches a nutritional composition comprising the claimed components, where the claimed amounts of each component are directly taught by, or rendered obvious by the prior art. The growth promoting effect of each component would have been expected to be synergistic when combined since said components are recognized to contribute to an optimized environment for Bifidobacteria growth (i.e., as metabolites and pH adjusters), where optimization of multiple environmental parameters would have synergistically promoted intestinal bacteria proliferation over that of a single parameter, with a reasonable expectation of success. This is particularly since Applicant discloses “a symbiotic, improved or synergistic effect is to be expected from urea together with non-digestible oligosaccharides”. Additionally, the data disclosed by the specification is not sufficient to show unexpected results (see response to arguments in the Non-Final rejection of 9/17/2025).
Regarding claim 27, the combination applied to claim 1 teaches the claimed limitations and a synergistic effect with respect to stimulating growth of intestinal Bifidobacteria is to be expected as stated for claim 25. One of ordinary skill would have similarly expected the composition of the prior art combination to stimulate growth of microbiota compared to a composition that does not comprise the claimed components for the same reasons stated for claim 25.
Response to Arguments
Applicant's arguments filed 12/10/2025 have been fully considered but they are not persuasive.
Applicant argues on page 5 that Nutricia targets C-section infants who lack Bifidobacterium species in the gut, whereas Wiklund explicitly teaches using an ammonium compound and omitting urea, and therefore one of ordinary skill would not have made the combination due to the contradictory teachings.
This is not persuasive since the portion of Nutricia cited by Applicant is directed to the findings of prior art not relied upon in the combination. Nutricia itself indicates that C-section infants have reduced rate of intestinal colonization by Bifidobacteria and less diverse microbiota relative to infants born vaginally, and aims to address the issue from birth until Bifidobacterium population recovers (page 2 line 30 to page 3 line 15). The Bifidobacterium population recovers within a period of days to weeks when the infant is supplemented with prebiotics (figures 1-2; page 3 lines 17-23). Further, the composition itself includes Bifidobacterium.
Wiklund teaches the composition comprising urea is intended for administration to an infant during the first month of life (column 5 lines 17-22). The reference further teaches both ammonia and urea can be administered simultaneously (column 5 line 38-40). Therefore, the cited prior art suggests that urea can be added to the composition of Nutricia after increased colonization of Bifidobacterium occurs e.g., 2-3 days, or together with ammonia immediately after birth. Additionally, the portion of Wiklund cited by Applicant is directed to a preferred embodiment, where the reference nonetheless teaches adding urea for the advantages stated in the prior art rejection.
Applicant argues on page 6 the combination does not teach the claimed ranges of urea, teaches a lower part of the concentration ranges when using both ammonium and urea, and states the amount of urea in example 2 of Wiklund falls below the claimed range.
This is not persuasive since one of ordinary skill in the art would have considered the “lower part” of the range to encompass more than the lower boundary value. The “lower part” of 1-10 mmol/l, given its broadest reasonable interpretation, would have encompassed all values below 5 mmol/l. Regardless, example 2 teaches 25 mg per 100 ml as recognized by Applicant, which is within the claimed range of 15-75 mg per 100 ml.
Applicant argues on page 6 that the teachings of McCoy cannot be applied to the infant gut environment since the reference is directed to dairy starters for cheese and the experiments are conducted under aerobic conditions, whereas Applicant’s experiments were conducted at 37oC under anaerobic conditions. Therefore, one of ordinary skill would not extrapolate McCoy’s findings to predict effects in the infant gut.
This is not persuasive since Applicant’s specification states the synergistic effect is achieved by urease-positive Bifidobacteria that “will beneficially affect the growth of other Bifidobacterium strains that are urease negative, by producing the growth factor CO2 and by releasing ammonium as nitrogen source. This released CO2 and ammonia can then be used by urease negative Bifidobacteria resulting in a more diverse and further improved microbiota.” (page 19 lines 5-12). McCoy shows urease positive Bifidobacteria hydrolyzes urea into ammonia and carbon dioxide which in turn promotes growth of bacteria. This is the same mechanism disclosed by Applicant, and would have been expected to naturally occur in the presence of urea and conditions suitable for Bifidobacteria growth. The reference is analogous since it is directed to growth of Bifidobacteria in foods and addresses the mechanism by which the bacteria and urea interact. Nutricia already teaches the composition comprises urease positive B. longum spp infantis and urease negative B. breve (page 5 lines 24-25). Since the prior art combination modifies Nutricia to include urea in the claimed amounts, one of ordinary skill in the art would have expected the same mechanism to occur in the infant gut when the modified composition is administered, where the ammonia and CO2 produced by the urease positive Bifidobacteria would be used by the urease negative Bifidobacteria for growth.
Applicant argues on pages 7-8 that examples 3-4 show synergy rather than mere additive benefits, table 3 demonstrates criticality, and none of the cited references would have led the skilled person to expect the synergistic effects. Applicant’s argument against Wiklund is addressed above.
This is not persuasive since the alleged synergistic effects would have been expected by the prior art as stated in the previous Office Action and explained above. Nutricia teaches non-digestible oligosaccharides facilitate growth of desirable intestinal microbiota, where it is important to improve and/or accelerate developing the appropriate bifidobacterial population and Bifidobacterium species in infants, where improving gastrointestinal Bifidobacterium population and diversity of species provides multiple health benefits.
The data of Applicant’s examples 3-4 appear to indicate that “the best growth is observed only in the presence of a combination of non-digestible oligosaccharides as a carbon source and urea as both nitrogen and CO2 source” (page 19 lines 1-2). This indicates to one of ordinary skill that the observed synergistic result of Bifidobacterium growth is a direct product of said oligosaccharides and urea present within the composition. Since the prior art combination teaches an infant formula comprising the claimed substances in amounts within the claimed ranges, one of ordinary skill in the art would have reasonably expected a similar synergistic effect to be observed with the formula of the prior art combination.
A compound and its properties are inseparable. In re Papesch, 137 USPQ 43 (CCPA 1963). Applicant’s disclosure indicates the argued result is due to the presence of urea and oligosaccharides. The prior art combination teaches said compounds in the claimed amounts, and recognizes the same hydrolysis process occurs with protease positive Bifidobacteria. Thus, the prior art composition would be expected to behave in the manner argued by Applicant.
Examples 3 and 4 provide results on the basis of concentration i.e., 10, 50, and 100 mM urea (pages 18-19 tables 3-4), where 10 mM urea corresponds to 60 mg per 100 ml (page 18 lines 14-15). The 50 and 100 mM (300 mg per 100 ml and 600 mg per 100 ml) are outside of the claimed range of 15-75 mg per 100 ml. Thus, the examples provide only a single data point within the claimed range. Allegations of unexpected results are evaluated on the criteria set forth in MPEP 716.02(d): “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the ‘objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.’ In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range.” In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). Further, “to establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960).” One of ordinary skill would not have been able to determine from the data whether or not the alleged results are observed at the lower and upper ends of the claimed ranges.
Applicant argues Buck does not teach 2’FL for synergistic Bifidobacteria growth.
This is not persuasive since Nutricia is modified to include 2’FL for the advantage of reduced inflammation and thus improved airway defense mechanisms and overall airway respiratory health in an infant as stated for claim 1. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Further, example 4 shows that urease positive Bifidobacteria “hardly grow in the absence of both CO2 and urea”, where growth is restored in the absence of CO2 by the presence of 2’FL and urea (page 19 lines 29-30). The lack of growth is attributed to the limited presence of a carbon and energy source, and the results indicate that “the type of non-digestible oligosaccharides is not crucial for their effect on growth in the presence of urea” provided they can be used as a carbon and energy source (page 20 lines 1-4). Thus, the example simply shows that 2’FL can be used as a carbon and energy source. One of ordinary skill would not have been able to determine if 2’FL synergizes with urea and the Bifidobacteria as argued. The results of Bifidobacteria growth would have been expected since 2’FL is an oligosaccharide which would provide the carbon and energy source while urea provides the nitrogen and CO2 as explained above. Additionally, the data is not commensurate in scope with the claimed range.
Applicant argues that one of ordinary skill would not have expected the cross-feeding and synergistic effects disclosed by the instant application.
This is not persuasive since the prior art shows such effects would have been expected. Nutricia teaches colonization of at least one Bifidobacterium species promotes intestinal colonization of other species (page 6 line 31 to page 7 line 6). It is further desirable to improve and/or accelerate developing the appropriate bifidobacterial population and Bifidobacterium species in infants, where improving gastrointestinal Bifidobacterium population and diversity of species provides multiple health benefits (page 4 lines 12-28). Thus, the reference suggests that colonization of the gut with at least one urease-positive Bifidobacterium species would facilitate proliferation and colonization of other urease-negative bacterium naturally present within the gut i.e., “cross-feeding”. The synergistic effect would have been expected as stated above.
Applicant’s argument against the dependent claims is not persuasive for the same reasons stated above.
Conclusion
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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/BRYAN KIM/Examiner, Art Unit 1792