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 status
Claims 34, 38-44 and 48-53 are pending following the Reply filed 06/17/2026. Claims 35-37 and 45-47 have been cancelled. Claims 34, 44 and 48 have been amended without introducing new matter. Claims 34, 38-44 and 48-53 are presently considered.
Withdrawn
The objection to the drawings is withdrawn in light of the Replacement Drawings filed 06/17/2026 and the amendments to the specification.
Any objection to or rejection of claims 35-37 and 45-47 is moot because the claims have been cancelled.
The objection to claims 34 and 44 are withdrawn in light of the amendments.
The enablement rejection under 35 U.S.C. 112(a) regarding the availability of the claimed biological deposits is withdrawn in light of the Declaration filed 06/17/2026. See Response to Declaration for further discussion.
However, upon further consideration, the Scope of Enablement rejection is maintained and extended to include claim 39, based on a new grounds of rejection. See the rejection below and Response to Arguments for further discussion.
The rejections under 35 U.S.C. 102 and 35 U.S.C. 103 are withdrawn in light of the amendments. In particular, the claims now require the deposited strains of NK210 and/or NK219. See Response to Arguments and Conclusion for further discussion.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
Claims 34 and 38-43 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating an inflammatory bowel disease, including Crohn’s disease and colitis, does not reasonably provide enablement for a method of treating Behcet’s disease or any inflammatory disease or any cognitive dysfunction. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Enablement requires that the specification teach those in the art to make and use the invention without undue experimentation. Factors to be considered in determining whether a disclosure would require undue experimentation include (1) the nature of the invention, (2) the state of the prior art, (3) the predictability or lack thereof in the art, (4) the amount of direction or guidance present, (5) the presence or absence of working examples, (6) the quantity of experimentation necessary, (7) the relative skill of those in the art, and (8) the breadth of the claims.
The nature of the invention / Breadth of the claims
All questions of enablement are evaluated against the claimed subject matter. When considering whether claims in a utility patent application or patent are enabled, USPTO personnel will use the Wands factors to ascertain whether the amount of experimentation required to enable the full scope of the claimed invention is reasonable. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). See also MPEP § 2164.01(a). The focus of the examination inquiry is whether everything within the scope of the claim is enabled. Accordingly, the first analytical step requires that the examiner determine exactly what subject matter is encompassed by the claims.
The broadest reasonable interpretation of independent claim 34 includes preventing any inflammatory disease or any cognitive dysfunction in a subject in need thereof by administering the claimed bacterial strains, NK210 and/or NK219.
In view of the dependent claims, an inflammatory disease may include, for example, diabetes, nephritis, obesity, sepsis, burns, arthritis, spondylitis, pancreatitis (claim 38) or Behcet’s Disease (claim 39), and a cognitive dysfunction may include, for example, Alzheimer’s disease, Huntington’s disease, depression, anxiety, Parkinson’s disease or dementia (see claim 40). The remainder of the rejected claims have a broader scope and effectively encompass any inflammatory disease or any cognitive dysfunction, while also including the conditions recited in claims 38 and 40, which are exemplified in the examiner’s discussion of the prior art below.
The amount of direction or guidance present
The specification states that an “inflammatory disease” is a collective term for a disease in which inflammation is the primary lesion and may be at least one selected from the group consisting of inflammatory bowel disease, arthritis, gout, hepatitis, asthma, obesity, keratitis, gastritis, nephritis, colitis, diabetes, tuberculosis, bronchitis, pleurisy, peritonitis, spondylitis, pancreatitis, urethritis, cystitis, vaginitis, arteriosclerosis, sepsis, burns, dermatitis, periodontitis, and gingivitis (see pg. 10, para. [39]). It should be noted that “Behcet’s disease” is listed as an “inflammatory bowel disease” in the claims, but in view of the art, discussed below, this disease is systemic and not limited to the gastrointestinal system.
The specification states that a “cognitive dysfunction” refers to a disorder characterized by cognitive impairment and behavioral changes, resulting from a decrease in functions such as memory, spatial perception, judgment, executive function, and language. The cognitive dysfunction may be selected from, but is not limited to, the group consisting of, for example, anxiety, depression, migraine, stress, Alzheimer's disease, Huntington's disease, vascular dementia, Pick's disease, Parkinson's disease, Creutzfeldt-Jakob, disease, dementia, and a combination thereof (see pg. 12, para. [44]).
The specification states that increasing the level of target good bacteria by changing the gut microflora is essential for improving complex health functions. “To achieve this, it is imperative for deriving an appropriate strain from countless strains, but it is very difficult to find these specific strains.” See pg. 3, para. [5]. Further, the probiotics according to the present disclosure have high utility as a medicine or food and, in particular, can be used for preventing, treating, or relieving inflammatory diseases and cognitive dysfunction and for improving immune function, due to having “an excellent antioxidant effect, inflammation-relieving effect, nerve improving effect, cognition-improving effect, gut microbiota imbalance-improving effect, immune-regulating effect, etc.” (see pg. 33, para. [120]). The specification also states that while the pharmaceutical composition of the present disclosure may be administered orally or parenterally, oral administration is preferred (see pg. 25 para. [89]).
The specification states that the claimed bacterial strains are also “effective in preventing or treating cognitive dysfunction by increasing the expression of brain-derived neurotrophic factor (BDNF) and increasing the expression of neuropeptide Y, which is highly associated with stress, anxiety, depression, and cognitive impairment” (see pg. 16, para. [61]).
The presence or absence of working examples
In Applicant’s Examples, the effect of administration in improving colitis was confirmed through changes in intestinal length, expression of inflammatory factors, and MPO activity. Specifically, the decrease in intestinal length was improved, MPO activity was decreased, and the expression of IFN-γ, TNF-α, and IL-10, which were suppressed by anticancer drugs, all increased. In particular, colitis was improved by increasing the expression of IL-10 compared to IFN-γ and IL-10 compared to TNF-α. See instant specification at page 57, para. [196].
Further, the administration of the strain according to the present disclosure showed improvement effects in both the Y-maze task and the NOR task. In particular, this improvement effect showed a synergistic effect when the strains were used in combination. In addition, there was an improvement on neuritis by improving the inflammatory indicators of the hippocampus, and in particular, lowering the levels of IFN-γ and TNF-α increased by endotoxin, increasing the expression of IL-10, and increasing the expression of IL-10 compared to IFN-γ and IL-10 compared to TNF-α. See instant specification at page 64, para. [214].
Finally, both Lactobacillus rhamnosus NK210 and Bifidobacterium longum NK219 were found to exhibit “excellent” antioxidant activity, anti-inflammatory efficacy, neurological enhancement, and inhibition in proliferation of intestinal Clostridium difficile and LPS production (see pg. 41, para. [145]).
However, examples 1-5 are directed to experiments conducted in vitro, and therefore did not involve the actual oral administration of the claimed strains to a subject. In particular, the effect of BDNF expression was assessed by introducing the claimed bacteria into SH-SY5Y cell cultures, and the effect of neuropeptide Y (NPY) expression was assessed by introducing the claimed bacteria into PC12 phaeochromocytoma cell cultures (see pg. 38-39, paras. [136]-[139]). Therefore, these tests required directly contacting the bacteria with these cells, which are typically used to model neurons in neurodegenerative disease. These cells do not appear to be associated with gastrointestinal cells or to be typically used to model responses in the gastrointestinal system. Therefore, orally administering a probiotic, such as the claimed bacterial strains, would not be expected to directly correlate in vivo to the same in vitro conditions of these experiments, and it is uncertain whether these results would achieve the same effects when orally administering the probiotics. See discussion regarding the prior art of Zuccato, et al. below for further discussion.
Furthermore, the results of the in vivo experiments of Applicant’s disclosure appear to have been limited to measurements in the brain, spleen and gut (see Examples 6-10 on pages 50-72), and the mice used in these experiments had only one of the following induced states: systemic inflammation induced by intraperitoneal injection of E. coli derived LPS (Example 6); immunosuppression induced by intraperitoneal injection of the anti-cancer drug, cyclophosphamide (Example 7); reduction in normal flora induced by oral administration of the antibiotic, ampicillin (Example 8); a healthy animal with no induced state (Example 9); and colitis induced by TNBS (Example 10).
Therefore, these results are based primarily on the presence of certain immune system factors in the brain, spleen or colon, as well general cognitive changes, in mice simulated to experience inflammation, immunosuppression, post-antibiotic effects, and colitis. The specification seems to consider, for example, that administering LPS or ampicillin induces “intestinal and brain diseases” (see pg. 50, para. [182]; pg. 60, para. [205]), but it is not apparent what brain diseases recited in the claims (e.g., Huntington’s Disease, Parkinson’s, Alzheimer’s, etc.) can reliably be correlated to this model. Furthermore, it is not apparent what “brain diseases” are induced by “ampicillin” (i.e., antibiotics). Thus, these experiments do not provide sufficient evidence to support that the claimed method could treat any cognitive dysfunction, particularly where the diseases recited in the claims were not actually modelled in the mice.
The state of the prior art / The predictability or lack thereof in the art
Regarding inflammatory diseases, Mu, et al. teach that perturbation of gut microbiota is known to promote autoimmune disorders that include inflammatory bowel disease, type 1 diabetes, rheumatoid arthritis, and multiple sclerosis (see pg. 1, col. 1). Mu demonstrates the potential of controlling lupus nephritis in mice using a mixture of five Lactobacillus bacteria, but concludes that future studies are warranted to determine if these results can be replicated in human subjects (see Abstract).
However, in a systematic review and meta-analysis of randomized controlled trials assessing the effect of probiotics supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis (SpA), or psoriatic arthritis), after excluding high-risk-of-bias trials of meta-analysis, there was no difference between probiotics and placebo, and the studies on SpA patients showed no efficacy of probiotics. In conclusion, probiotic supplementation might decrease rheumatoid arthritis activity, “but lack of evidence and studies’ heterogeneity do not allow us to propose them to patients with inflammatory arthritis to control their disease”. See Sanchez, et al. (Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2022 Jan 14;14(2):354; cited on Form 892) at Abstract.
Khailova, et al. (Probiotic administration reduces mortality and improves intestinal epithelial homeostasis in experimental sepsis. Anesthesiology. 2013 Jul;119(1):166-77; cited on Form 892) evaluated the effects of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum (BL) on mortality, bacterial translocation, intestinal epithelial homeostasis and inflammatory response in experimental model of septic peritonitis, finding that the probiotics led to significant reductions in systemic and colonic inflammatory cytokine expression versus septic animals (in mice) (see Abstract). However, one recent clinical trial studying probiotics in severe pancreatitis (the PROPATRIA trial) found an unexpected increase in mortality in probiotic-treated patients, and it is possible that the postpyloric administration of this fiber/multiple probiotic strain mixture in pancreatitis patients may carry significant risk and should likely be avoided (see pg. 9, para. 5 to pg. 10, para. 1).
Askari, et al. (Synbiotic Supplementation May Relieve Anterior Uveitis, an Ocular Manifestation in Behcet's Syndrome. Am J Case Rep. 2019 Apr 19;20:548-550; cited on Form 892) discloses that to relieve the signs and symptoms of anterior uveitis (AU), an ocular manifestation of Behcet’s syndrome, a synbiotic supplementation (probiotics and prebiotics) was prescribed for a 49-year-old woman (See background). Seven strains of bacteria –Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, Lactobacillus acidophilus, Bifidobacterium longum, and Lactobacillus bulgaricus, each 108 colony-forming units (CFU) – and fructo-oligosaccharide (FOS; 100 mg) were given as a capsule 2 times per day. After 7-month treatment, AU was improved and serum inflammatory markers – C-reactive protein (CRP), highsensitivity CRP (hs-CRP), and estimated sedimentation rate (ESR) – were suppressed (see Case Report). However, the results of the study conflict with some previous reports: one study observed the relative abundance of genera
Bifidobacterium, Eggerthella and Lactobacillus species in BD patients compared to normal adults, and considered this condition as a dysbiosis, and another study reported the rapid onset of rheumatoid arthritis in germ-free mice, induced by oral intake of Lactobacillus bifidus. See pg. 550, col. 1, para. 2 to col. 2, para. 1.
Hence, while there appears to be some success in the art when treating inflammatory diseases by the oral administration of lactic acid bacteria, such as certain strains of Lactobacillus and Bifidobacterium, it is not clearly predictable which oral probiotics, in which combinations, will have the desired effects of ameliorating symptoms or reducing pathology in this broad range of diseases. In some cases, these positive effects are not present at all, and in other cases the bacteria may actually worsen the patient’s condition. Furthermore, many of these studies utilize a complex mix of many probiotics, not just one or two strains, and researchers stress the need for further research before considering such treatments in humans.
Therefore, in order for one to determine which inflammatory diseases are treatable, one must discover for themselves which embodiments of the invention are operable and which are not. Given the breadth of inflammatory diseases and their diverse range of pathologies, as well as the potential for numerous different co-treatments (e.g. additional probiotics, prebiotics, medication, etc.) in order to be successful, the amount of further experimentation required to practice the full scope of the claimed method would require more than a routine amount of effort.
Regarding cognitive dysfunction, Zhu, et al. (Probiotics for Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis. Foods. 2021 Jul 20;10(7):1672; cited on Form 892) teaches that accumulating evidence from animal studies supports the potential role of probiotics and prebiotics in alleviating neurodegenerative diseases. However, whether dietary supplementation with probiotics improves cognitive function in patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI) is unclear. See Abstract. “Given that certain probiotic strains have synergistic effects on the gut microbiota, multistrain probiotics that promise high efficacy should receive more attention in future studies” (see pg. 12, para. 6). Zhu concludes that given the insufficient evidence from current random controlled trials (RCTs), further work concerning long-period, large-scale RCTs is warranted to investigate the neuroprotective effects of probiotics in different stages of AD (see pg. 13, para. 4).
Cenit, et al. (Influence of gut microbiota on neuropsychiatric disorders. World J Gastroenterol. 2017 Aug 14;23(30):5486-5498; cited on Form 892) discloses that a number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson’s disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. See Abstract. “Surprisingly, so far there is a lack of detailed analyses of the microbiota of patients with AD.” However, in metabolic syndrome, type 2 diabetes and obesity, which are risk factors for AD, there is an alteration in the gut microbiota. See pg. 5494, col. 2, para. 2. “However, there is a need of further work to elucidate the specific gut’s microbes and the mechanisms involved in the link between obesity, T2D and AD” (see pg. 5494, col. 2, para. 3). Cenit concludes that while inflammation seems to be a critical pathophysiological feature of mental disorders and, therefore, a potential target for microbiota-based interventions, “further knowledge is needed on how microbiota signals generated in the gut can impact on microglial activation and neuroinflammation” (see pg. 5495, col. 1, para. 2).
Reis, et al. (The anxiolytic effect of probiotics: A systematic review and meta-analysis of the clinical and preclinical literature. PLoS One. 2018 Jun 20;13(6):e0199041; cited on Form 892) discloses that while probiotics have generated intensive research interest in recent years as a novel mode of treatment for physical and mental illness, the anxiolytic potential of probiotics remains unclear, i.e., regarding the effect of probiotic administration on anxiety (see Background). After extracting data from 22 preclinical studies (743 animals) and 14 clinic studies (1527 individuals), species-level analyses identified only Lactobacillus rhamnosus as an anxiolytic species, but these analyses were broadly under-powered. Overall, probiotics reduced anxiety-like behavior in animals but did not significantly reduce symptoms of anxiety in humans. See Results. Reis notes that while Lactobacillus and Bifidobacterium species of bacteria are the most commonly investigated probiotics, the different species are not identical, and even strains within the same species can have unique effects on the body. In one case, a species of Lactobacillus was shown to increase anxiety-like behavior in rodents. Because of this, candidate probiotics require extensive study and characterization prior to clinical application. See pg. 16, para. 3.
Romijn, et al. (A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression. Aust N Z J Psychiatry. 2017 Aug;51(8):810-821; cited on Form 892) investigated whether probiotics improved mood, stress and anxiety in a sample selected for low mood, and also tested whether the presence or severity of irritable bowel syndrome symptoms, and levels of proinflammatory cytokines, brain-derived neurotrophic factor and other blood markers, would predict or impact treatment response (see Abstract, Objectives). Seventy-nine participants (10 dropouts) not currently taking psychotropic medications with at least moderate scores on self-report mood measures were randomly allocated to receive either a probiotic preparation (containing Lactobacillus helveticus and Bifidobacterium longum) or a matched placebo, in a double-blind trial for 8 weeks (see Abstract, Method). However, the study found no evidence that the probiotic formulation is effective in treating low mood, or in moderating the levels of inflammatory and other biomarkers. The lack of observed effect on mood symptoms may be due to the severity, chronicity or treatment resistance of the sample; recruiting an antidepressant-naive sample experiencing mild, acute symptoms of low mood, may well yield a different result. Future studies taking a preventative approach or using probiotics as an adjuvant treatment may also be more effective. See Abstract, Conclusions. It should be noted that the probiotic formulation used in this trial had previously shown positive effects on both emotional behaviors in animal studies (see pg. 819, col. 1, para. 3).
In view of Zuccato et al. (previously cited), BDNF is a small dimeric protein that is widely expressed in the adult mammalian brain and has been shown to promote the survival of all major neuronal types affected in Alzheimer’s disease (AD) and Parkinson’s disease (PD) (see Abstract). Zuccato teaches that the normal huntingtin protein, whose mutation causes Huntington’s Disease (HD), is involved in the physiological control of BDNF synthesis and transport in the brain, sustaining cortical BDNF gene transcription and driving BDNF vesicle sorting in neuronal cells, whereas both processes are simultaneously disrupted in HD. Zuccato discloses that it is possible that increasing endogenous BDNF production or supplying exogenous BDNF may have therapeutic effects if applied in an appropriate spatio-temporal context (see pg. 320, col. 2, para. 3).
Hence, while there appears to be some correlation between cognitive dysfunction and the microbiome, as is being actively investigated in the art, it is not clearly predictable which oral probiotics, in which combinations, will have the desired effects of ameliorating symptoms or reducing pathology in this broad range of diseases. In many cases, these positive effects are not present in humans at all and frequently do not translate well from animal studies. Furthermore, the signals between these different systems of the human body (i.e., gut-brain axis) is complex, and successfully treating any of the recited cognitive conditions may depend not only on the individual, but also the stage of the disease and its particular pathology. Given the complexity of these disease states and bodily systems, as well as the limited knowledge as to how microbial signals in the gut impact neuroinflammation, it is not clear whether the levels of certain immune system inflammatory factors, as disclosed in Applicant’s examples, can reliably be used to predict an efficacious treatment. In particular, it is uncertain whether the BDNF or NPY expression of neuron-modelling cells co-cultured with the probiotics is in any way correlative to the effects of applying these probiotics to the gut.
Therefore, in order for one to determine which cognitive dysfunctions are treatable, one must discover for themselves which embodiments of the invention are operable and which are not. Given the enormous breadth of complex cognitive dysfunctions and their diverse range of pathologies in the art, as well as the potential for numerous different co-treatments (e.g. additional probiotics, prebiotics, medication, etc.) in order to be successful, the amount of further experimentation required to practice the full scope of the claimed method would require more than a routine amount of effort.
The quantity of experimentation necessary / The relative skill of those in the art
While the level of skill in the art is high, the predictability in the art is low, as is shown in the review of prior art above. Therefore, a skilled artisan would have reasonably expected an amount of experimentation commensurate with making substantial inventive contributions over the prior art of record in order to practice the full scope of the claimed method. Due to the lack of substantive evidence and specific guidance in the instant disclosure and the prior art, one of ordinary skill at the time of filing would have found it to be highly unpredictable which individuals would have been treatable using the claimed method, and what modifications would have to be made in order to practice its full scope, therefore requiring an undue amount of experimentation in order to be successful.
Conclusion
“Enabling the full scope of each claim is part of the quid pro quo of the patent bargain. A patentee who chooses broad claim language must make sure the broad claims are fully enabled. The scope of the claims must be less than or equal to the scope of the enablement to ensure that the public knowledge is enriched by the patent specification to a degree at least commensurate with the scope of the claims.” Sitrick v. Dreamworks, LLC, 516 F.3d 993, 999 (Fed. Cir. 2008).
In deciding In re Fisher, 166 USPQ 18, 24 (CCPA 1970), the Court indicated the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. “Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC 1997).
In conclusion, upon careful consideration of the factors used to determine whether undue experimentation is required, in accordance with the Federal Circuit decision of In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988), the amount of guidance, direction, and exemplification disclosed in the specification, as filed, is not deemed sufficient to have enabled the skilled artisan to make and/or use the full scope of the claimed invention at the time the application was filed without undue and/or unreasonable experimentation.
Response to Declaration
The declaration under 37 CFR 1.132 filed 06/17/2026 (2 pages) is sufficient to overcome the enablement rejection of claims 34, 38-44 and 48-53 under 35 U.S.C. 112(a) based upon the availability of the biological deposits recited in the claims.
The declaration provides the identifying information of the claimed deposited strains and a statement over the signature of the inventor, stating that the deposit has been made under the terms of the Budapest Treaty and that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent.
The declaration also states that the material has been deposited under conditions that assure that access to the material will be available during the pendency of the patent application to one determined by the Commissioner to be entitled thereto under 37 C.F.R. 1.14 and 35 U.S.C. 122. Further, the deposit will be maintained for a term of at least thirty (30) years and at least five (5) years after the most recent request for the furnishing of a sample of the deposited material. Further, the duty to replace the deposit should the depository be unable to furnish a sample when requested due to the condition of the deposit is also acknowledged.
In addition, the identifying information set forth in 37 CFR 1.809(d) has been added to the specification by the amendment filed 06/17/2026.
Therefore, the requirements under 37 CFR 1.803 - 37 CFR 1.809 are considered to have been met.
The examiner suggests that the locations of the depositories should also be included in the claims where the deposited strains are recited.
In view of the foregoing, the rejections above have been withdrawn.
Response to Arguments
Regarding the Scope of Enablement rejection under 35 U.S.C. 112(a), Applicant argues that the amended claim scope is squarely within the enabled scope the Office Action identified: methods of treating inflammatory disease and cognitive dysfunction are directly demonstrated by the working examples in the specification, including improvement of colitis through regulation of cytokine expression (see specification at pg. 57, para. [196]) and improvement of cognitive function through Y-maze and NOR tasks and modulation of hippocampal BDNF and NPY expression (see specification at pg. 64, para. [214]). Because the "preventing" language resided solely in independent claim 34, its deletion brings dependent claims 38 and 40-43 within the enabled scope as well.
Applicant’s arguments with respect to claim(s) 34, 38 and 40-43 have been considered but are moot because, upon further consideration, a new grounds of rejection is made against claims 34 and 38-43 under 35 U.S.C. 112(a).
As discussed in the new scope of enablement rejection, the specification, while being enabling for a method of treating an inflammatory bowel disease, including colitis, does not reasonably provide enablement for a method of treating Behcet’s disease or any inflammatory disease or any cognitive dysfunction. The examiner’s reasonings for this conclusion are set forth in the present rejection.
In particular, the modulation of hippocampal BDNF and NPY expression modeled in the inventor’s experiments is not considered to be sufficient to overcome the lack of predictability in the prior art of record for a method for treating the recited cognitive impairments (i.e., Alzheimer’s, Parkinson’s and Huntington’s disease), because there is sufficient doubt regarding how the inventor’s in vitro experiments would correlate to a successful treatment when administering the bacterial strains as probiotics. See the present rejection for further discussion.
Regarding the rejections under 35 U.S.C. 102, Applicant argues that Rogulja does not disclose, teach, or suggest Lactobacillus rhamnosus NK210 or Bifidobacterium longum NK219, or any strain having a 16S rDNA sequence corresponding to instant SEQ ID NOs
1 or 2.
Applicant’s arguments have been fully considered and are persuasive.
The deposited strains are disclosed in the specification as comprising the 16S rDNA sequences according to SEQ ID NOs 1 and 2, and the examiner has found no evidence that Rogulja teaches any strain comprising an equivalent structure. Accordingly, the rejection has been withdrawn.
Regarding the rejections under 35 U.S.C. 103, Applicant argues that neither Park nor GenBank CP033606.1 discloses, teaches, or suggests Lactobacillus rhamnosus NK210 (KCCM13049P, SEQ ID NO: 1) or Bifidobacterium longum NK219 (KCCM13050P, SEQ ID NO: 2). These are entirely different bacterial species with distinct 16S rDNA sequences.
Applicant’s arguments have been fully considered and are persuasive.
The deposited strains are disclosed in the specification as comprising the 16S rDNA sequences according to the SEQ ID NOs 1 and 2, and the examiner has found no evidence that either reference teaches any strain comprising an equivalent structure. Accordingly, the rejection has been withdrawn.
Conclusion
Claims 44 and 48-53 are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Cook et al. (US 2023/0068960 A1, effectively filed 09/24/2019; previously cited) teach a method for treating or preventing a disease, disorder, or condition associated with one or more of dysbiosis of the intestinal microbiome, inflammation, infection, allergy, or immune dysfunction in a subject in need thereof, the method comprising administering to the subject (i) a prebiotic mixture comprising one or more human milk oligosaccharides and (ii) at least one probiotic strain of bacterium comprising B. longum subsp. longum (see claim 1), wherein the disease, disorder, or condition comprises one or more of obesity, type II diabetes, a chronic inflammatory disease, an autoimmune disease (see claim 9), or inflammatory bowel disease (see claim 10). In certain embodiments, the at least one probiotic strain may be L. rhamnosus, Bifidobacterium longum subsp. longum, and Lactococcus lactis (see pg. 19, para. [0176]). Cook discloses exemplary full or partial 16S sequences for L. rhamnosus (SEQ ID NO: 33), B. longum subsp. longum (SEQ ID NO: 14), and L. lactis (SEQ ID NO: 43).
However, the 16S sequences taught by Cook are not identical to instant SEQ ID NOs 1, 2, and 3 of the present disclosure. As these sequences are disclosed in the instant specification as being structural characteristics of the bacterial strains deposited under KCCM13049P, KCCM13050P, and KCCM13048P, respectively, the claimed invention cannot be anticipated by Cook. Further, SEQ ID NO: 1 (KCCM13049P) and SEQ ID NO: 2 (KCCM13050P) are free of the prior art, so it would not have been obvious to have substituted an equivalent strain, because no strain having either of these sequences has been found in the prior art of record.
Thus, in the absence of evidence to the contrary, which is the initial burden of the examiner to establish, the methods of claims 34, 38-44 and 48-53, which comprise administering the strains deposited under accession numbers KCCM13049P and/or KCCM13050P, are free of the prior art of record and are nonobvious in view of the closest prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS ARMATO whose telephone number is (703)756-5348. The examiner can normally be reached Mon-Fri 11:00am-7:30pm EST.
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/DENNIS IGNATIUS ARMATO JR/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
