DETAILED ACTION
Applicant's response filed on December 10, 2025 has been entered.
Claims 1, 7, 12 and 18-22 are currently pending.
Allowable Subject Matter
Claims 7, 18, 21 and 22 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 12, 19 and 20 is/are rejected under 35 U.S.C. 103 as obvious over Masuyama et al (US 6,284,243), O’Hagan et al (Neurobiology of Learning and Memory, 2017, Vol. 144, pp. 36-47, provided by Applicants) and Gareau et al (Gut microbiota. 2011, 60: 307-317) in view of Uchida Naoto et al. (JP 2013/005757, 10/1/2013) and Kim et al (US 20180355445 A1; 12/13/18).
Masuyama et al teach a method for improving brain function or enhancing learning ability or memory comprising administering to a human or animal a physiologically functional food which comprises an affective amount of milk fermented with a lactic acid bacterium, milk co-fermented with a lactic acid bacterium and a yeast or a mixture thereof, wherein the lactic acid bacterium belongs to the genus Lactobacillus. They describe wherein the physiologically functional food is a fermented dairy product, fermented milk-blended processed drink, fermented milk-blended processed food, tablet, capsule, or granule. The method teaches, wherein the effective amount is at least 0.1 g/kg body weight/day. See abstract and claims 1-3. The effects of the functional food of the present invention on the brain function-improving, learning ability-enhancing and memory-enhancing functions can be confirmed by measuring the amount of 5-hydroxytryptamine (see claim 1 and paragraph 8 of the description). The fermented milk contains cells and a culture of Lactobacillus. That is, Document 1 discloses use of cells of 10 microorganism belonging to the genus Lactobacillus and culture thereof in preparation of a composition for improving a brain function or enhancing a learning ability or memory.
The lactic acid bacteria for use in the present invention as taught in the instant specification are not particularly limited as long as the active ingredient of the present invention can be provided, and they can be selected from known available lactic acid bacteria. Examples of the lactic acid bacteria include those which belong to the genera Streptococcus, Lactococcus, Lactobacillus, and Bifidobacterium. Specific examples include Streptococcus thermophilus, Lactococcus lactis (e.g., Lactococcus lactis subsp. lacti), Lactobacillus delbrueckii (e.g., Lactobacillus delbrueckii subsp. bulgaricus), Lactobacillus helveticus, Lactobacillus casei (e.g., Lactobacillus casei subsp. casei), Lactobacillus acidophilus, Lactobacillus fermentum, Bifidobacterium longum, and Bifidobacterium breve. More specific examples include Lactobacillus delbrueckii subsp. bulgaricus ATCC (American Type Culture Collection) 11842, Lactobacillus helveticus ATCC 55796 (corresponding to ATCC 15009), Lactobacillus casei subsp. casei ATCC 393, Lactobacillus acidophilus ATCC 4356, and Lactobacillus fermentum ATCC 14931. Among these, the genus Lactobacillus is preferably used, and Lactobacillus helveticus is more preferably used. Maysuyama et al teaches that all species of the bacteria of the genus Lactobacillus achieve the improved effect. The scope of improving memory and learning ability is for all ages and would include those with age related decline.
O’Hagan teach that ageing is associated with changes in the gut microbiome that may contribute to age-related changes in cognition. Previous work has shown that dietary supplements with multi-species live microorganisms can influence brain function, including induction of hippocampal synaptic plasticity and production of brain derived neurotrophic factor, in both young and aged rodents. However, the effect of such dietary supplements on memory processes has been less well documented, particularly in the context of aging. The main aim of the present study was to examine the impact of a long-term dietary supplement with a multi-species live Lactobacillus and Bifidobacteria mixture (Lactobacillus acidophilus CUL60, L. acidophilus CUL21, Bifidobacterium bifidum CUL20 and B. lactis CUL34) on tests of memory and behavioural flexibility in 15–17-month-old male rats. Following behavioural testing, the hippocampus and prefrontal cortex was extracted and analysed ex vivo using 1H nuclear magnetic resonance (1H NMR) spectroscopy to examine brain metabolites. The results showed a small beneficial effect of the dietary supplement on water maze spatial navigation and robust improvements in long-term object recognition memory and short-term memory for object-in-place associations. 1H NMR analysis revealed diet-related regional-specific changes in brain metabolites; which indicated changes in several pathways contributing to modulation of neural signaling. These data suggest that chronic dietary supplement with multi-species live microorganisms can alter brain metabolites in aging rats and have beneficial effects on memory. See abstract.
Gareau et al (see Discussion) teach the treatment of C. rodentium infected mice with a combination of Lactobacillus-containing probiotics prevented stress-induced memory deficits, ameliorated serum corticosterone levels and colonic epithelial crypt hyperplasia. The benefit was attributed at least in part with restoration of hippocampal BDNF and c0Fos expression in the context of a normalized microbiota. Germ-free mice displayed absence of non-spatial and working memory, indicating the requirement for a commensal gut microbiota in memory. Corticosterone levels and brain expression of glucocorticoid and mineralocorticoid receptors are essential for learning and memory, with alterations in HPA-axis function resulting in impaired hippocampal memory. Stress-induced memory deficits at 30 days after infection are novel and unexpected findings, because the pathogen has cleared and all colonic parameters, except enteroendocrine cell signaling, have returned to normal. Taken together, these findings suggest that an enteric bacterial infection, via either enteroendocrine cell serotonin or corticotrophin-releasing factor, primes the HPA axis so that exposure to a mild stressor is sufficient to elicit an abnormal behavioral response, resulting in altered memory. The presence of microbes is, therefore, crucial for the development of hippocampus-dependent memory, possibly owing to reduced expression of BDNF, as observed in the cortex in previous studies, and in the CA1 region in this study. Germfree mice also demonstrated a decrease in c-Fos expression, compared with colonized animals. In addition, an increase in baseline corticosterone, but with an absence of a hyper-responsive HPA-axis response in germ-free mice was observed, a finding which may relate to the strain of mouse and stressor type used in various studies. Since rearing in different facilities can also alter the gut microbiome of genetically identical mice, it is likely that the presence of a gut microbiome which regulates memory, and not the specific composition of the microbiota, that is the crucial determining factor. Taken together, these results emphasize that alterations in the composition of the intestinal microbiota exert a measurable impact on certain aspects of animal behavior, and that normalization of the microbiota can prevent behavioral abnormalities. Future studies should delineate the breadth of behaviors that are influenced by alterations in the intestinal microbiota.
Although the prior art references teach the use of any Lactobacillus spp. They do not particularly exemplify the use of Lactobacillus gasseri.
Uchida discloses a fermented milk composition, a food/drink item, and a supplement, etc., containing a peptide obtained by fermenting mammalian milk or milk protein using lactic acid bacteria or a processed product thereof. Uchida indicates that the peptide has a brain-function-improving effect and makes it possible to prevent amnesia and strengthen memory ability, and discloses using, as the lactic acid bacteria, Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus gallinarum, Lactobacillus johnsonii, Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium pseudolongum, Bifidobacterium bifidum, Bifidobactertum catenatum, Leuconostoc mesenteroides, Leuconostoc lactis, or Pediococcus pentosaceus, etc. (in particular, see claims, paragraphs [0008], [0017]-[0019], and [0057]-[0072], embodiments). Accordingly, the invention is anticipated. Alternatively, it would have been obvious for one of ordinary skill in the art to administer the composition comprising the L.gasseri for the intention of improving memory and ultimately learning ability.
Kim et al teach at paragraph [0017] that a certain Lactobacillus sp. strain according to the present invention is isolated from kimchi, and thus is highly safe, and has various physiological activities such as memory improvement activity, tight junction protein expression inducement activity, antioxidant activity, lipopolysaccharide (LPS) production inhibitory activity or β-glucuronidase inhibitory activity. Accordingly, a certain Lactobacillus sp. strain according to the present invention may be used as an ingredient of medicinal products or functional foods for preventing, alleviating or treating various diseases through combination of the strain's first effect that alleviates intestinal permeability and the secondary effect that improves learning ability or memory. Table 1 recites the use of Lactobacillus gasseri. At paragraph [0060] it is taught that in order to evaluate the effect of the lactic acid bacteria isolated from kimchi or human feces, on the alleviation of intestinal damage or internal permeability, the antioxidant activity, lipopolysaccharide (LPS) production inhibitory activity, β-glucuronidase (harmful intestinal enzyme) inhibitory activity, tight junction protein expression inducement activity and memory improvement activity of the lactic acid bacteria were measured.
The invention in claims 7, 21 and 22 differ from the prior art references in relating to a specific strain, e.g., strain SBT2056. Although the reference does not disclose the specific strain as strain SBT2056, it appears to be the same given its name and memory/learning, improving brain function abilities. If such cannot not be found to be the case then, they appear to be obvious or analogous variants since they possess similar functional characteristics and are of the same Genus and species.
Since the Patent Office does not have the facilities for examining and comparing applicants' product with the product of the prior art reference, the burden is on applicants to show an unobvious distinction between the material structural and functional characteristics of the claimed product and the product of the prior art. See In re Best, 562 F.2d 1252, 195 USP PQ 430 (CCPA 1977). Further, it would be obvious that although the strain of the prior art may not be the same, they appear to be obvious or analogous variants of the strain used by applicants since they possess similar functional characteristics and source. The use of a new or different strain of the same species for the purpose of maintaining and/or improving memory and learning ability would have been obvious to one of ordinary skill in the art. It is also noted that claims 1 12 and 20 do not require strain SBT2056, but allow for any L. gasseri strain. The references cited above teach that Lactobacillus and, more particularly L. gasseri, were well-known ingredients in probiotic compositions to improve memory and learning in all age groups and underlying etiologies, and particularly in fermented milk compositions. It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a composition comprising Lactobacillus, and more specifically L. gasseri, to maintain and/or or improve memory in learning ability in age (older populations) as well as any populations with memory loss/decline. While the claims were previously amended to recite that the decline does not include a decline in memory and/or learning ability due to diseases, e.g., Parkinson’s, Alzheimer’s, etc. (see claim 1) and specify they are treating age related decline, it is noted that the only experiments in the instant specification were in C. elegans and there is no comparison of the compositions with respect to populations with learning or memory ability due to age-related disease. Since the prior art teaches the use of these probiotics in both scenarios, it would have been prima facie obvious to use them to treat age-related decline.
Response to Applicants’ arguments:
Applicants argue that:
Figure 2 of the instant specification hows a statistically significant improvement between L. gasseri and other Lactobacillus species, including L. acidophilus, L. johnsonii, L. delbrueckii subsp. delbrueckii, and L. gallinarum.
Further, Applicant respectfully submits that Masuyama cannot be considered an enabling disclosure with respect to any species other than Lactobacillus helveticus. A person skilled in the art reading the description of Masuyama would not reasonably expect that species other than Lactobacillus helveticus would possess the same effect. In fact, the probiotic effects possessed by certain species within the Lactobacillus genus are not necessarily shared by other species within the same genus. To demonstrate this point, please see Hwang et al., enclosed. The abstract of Hwang states as follows: Most LAB cell wall extracts except those of L. plantarum and L. delbrueckii induced the proliferation of both immune cells at tested concentrations Of ten LAB extracts, four (from L. acidophilus, L. bulgaricus, L. casei, and S. thermophiles) promoted both cell proliferating and Tπ1 cytokine production. Hwang tested 10 types of lactic acid bacteria, 6 of which are species of Lactobacillus. Of these, only 4 types of bacteria, 3 of which are species of Lactobacillus had the properties of promoting cell proliferating and TH1 cytokine production. As such, it is inaccurate to presume that all members of the genus Lactobacillus will share the same effects.
Applicants also argue that:
In Kim, Lactobacillus gasseri (CH16 and CH26) is disclosed as a species that has no direct memory-improvement activity or therapeutic effect on Alzheimer's disease or Parkinson's disease. If Lactobacillus gasseri (CH16 and CH26) had such a therapeutic effect on disease or Parkinson's disease (like Lactobacillus curvatus CHS, Lactobacillus sakei CH11, Lactobacillus brevis CH23, Lactobacillus johnsonii CH32) it would have been listed in paragraph [0072], but it was not. This further demonstrates the differences among species within the genus Lactobacillus. Therefore, a person skilled in the art would not have had any reason to employ Lactobacillus gasseri in Masuyama, based on the disclosure of Kim.
These arguments have been fully and carefully considered but are not deemed persuasive as they are not commensurate in scope with the claimed invention in claims 1, 18, 19 and 20. As Applicants have noted, different strains have different effects. Figure 2 of the instant specification specifically uses L. gasseri strain strain SBT2056 (FERM BP-11038). Applicants have shown unexpected results with this particular strain (SBT2056) in the claimed methods which would make its particular use non-obvious as compared to the L.gasseri strains cited above.
THIS ACTION IS MADE FINAL. 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.
Prior art not presently, relied upon:
JP 2017-197486 A. 11/2/2017. Paragraph [0014] teaches strain SBT2056.
PAROIS, S. et al., The influence of a probiotic supplementation with Pediococcus acidilactici on memory in quail suggests a role of gut microbiota on cognitive abilities in birds, Behavioural Brain Research, 2017, Vol. 331, pp. 47-53.
Note: Japan Pat. No. 0923848A, Publication Date: January 28, 1997 is same as Masuyama et al (US Patent No. 6,284,243) cited above.
(JPH0923848A, Publication Date: January 28, 1997), as the closest prior art, discloses a method for improving brain function or enhancing learning ability or memory comprising administering to a human or animal a physiologically functional food which comprises an affective amount of milk fermented with a lactic acid bacterium, milk co-fermented with a lactic acid bacterium and a yeast or a mixture thereof, wherein the lactic 5 acid bacterium belongs to the genus Lactobacillus; the effects of the functional food of the present invention on the brain function-improving, learning ability-enhancing and memory-enhancing functions can be confirmed by measuring the amount of 5-hydroxytryptamine (see claim 1 and paragraph 8 of the description). The fermented milk contains cells and a culture of Lactobacillus. That is, Document 1 discloses use of cells of 10 microorganism belonging to the genus Lactobacillus and culture thereof in preparation of a composition for improving a brain function or enhancing a learning ability or memory.
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/JENNIFER E GRASER/Primary Examiner, Art Unit 1645 2/5/26