DETAILED ACTION
Status of claim rejections
The rejection of record under 35 USC 112(a) is maintained in view of Applicant’s amendments/arguments in the response filed 07/20/2026.
The double patenting rejections of record are withdrawn in view of Applicant’s arguments/amendments in the response filed 07/20/2026.
This Action is FINAL.
Maintained/Modified Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4, 6-10, 22-27 and 149-152 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 assaying for evaluating the effects of specific metabolites in cytokine production in a culture of human monocytes, does not reasonably provide enablement for improving at least one symptom of amyotrophic lateral sclerosis (ALS) in a mammalian subject. 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The claims, as amended, are drawn to a method of improving at least one symptom of a Vagus nerve-associated disease, disorder, or condition, the method comprising:
administering to a mammalian subject in need thereof a composition comprising microbial strains of Gluconacetobacter hansenii, Terrisporobacter glycolicus, Coprococcus catus, Lactobacillus plantarum, Veillonella atypica, and Bifidobacterium breve; wherein the Vagus nerve-associated disease, disorder, or condition is Amyotrophic lateral sclerosis (ALS). The level of skill in the art is high and would include, e.g., Ph.D. level scientists.
Martin et al. (Front. Cell. Infect. Microbiol., 12(839526):1-18 (2022), hereinafter “Martin”) evidences that ALS etiology and pathophysiology are not well understood (Abstract). Martin further evidences that “[a]lthough microbiome may indeed play a critical role in ALS pathogenesis, studies implicating innate immunity and intestinal changes in early disease pathology are limited” (Abstract). Martin evidences that “[l]ittle is known about the gastrointestinal (GI) changes in ALS patients before and after the diagnosis, although autonomic dysfunction is reported in ALS” (page 2, first column).
Blancher et al. (Nature, 572:474-480 (2019), hereinafter “Blancher”) evidences
that administration of Parabacteroides distastonis and Ruminococcus torques exacerbate ALS progression, while Akkermansia muciniphila ameliorated ALS symptoms in a limited mouse model (Abstract).
Di Gioia et al (BMC Medic., 18(153):1-19 (2020)) evidences that administration of a probiotic composition of Streptococcus thermophilus, Lactobacillus fermentum, Lactobacillus delbrueckii subsp. delbrueckii, Lactobacillus plantarum, and Lactobacillus salivarius to ALS patients failed to bring the biodiversity of intestinal microbiota of patients closer to that of control subjects and had no influence on the progression of the disease (Abstract; page 3, Probiotic supplement).
As such, the art offers no predictably for improving ALS in any mammalian subject through administration of various strains of probiotic/commensal bacteria.
The Specification only exemplifies and reduces to practice evaluating the effect of metabolites on LPS-induced cytokine production in human monocytes. The Specification offers no working examples or direction for improving of ALS in virtually any mammalian subject (humans, rats, mice, primates, etc.) through administration of the claimed microbial composition formulated, e.g., as eye drops or a topical composition. Nothing in the Specification remotely suggests that the claimed microbial composition would have any efficacy against symptoms of ALS. Instead, Applicant merely offers a cursory and speculative statement that “[t]he change in cytokine levels using metabolites in monocytes suggests that one or more of these metabolites may be used to modulate, reduce, or reverse inflammation (e.g. including neuroinflammation), which may in turn be used to treat and/or prevent diseases associated with the Vagus Nerve as described herein” (Specification, paragraph 0078, as published).
In view of the foregoing, a vast quantity of experimentation, including extensive clinical trials, would be needed to make or use the invention based on the content of the disclosure.
Taken together, 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 the claims.
Response to Arguments
Applicant's arguments filed 07/20/2026 have been fully considered but they are not persuasive.
On pg. 5-7 of the remarks, Applicant argues that the amendments of the claims is sufficient to overcome the enablement rejection. Specifically, Applicant argues that the scope of the claims are enabled by the specification and the experimental data from Exhibit A (previously submitted). Applicant argues
In response, the examiner disagrees. The scope of enablement rejection as set forth above and in previous Office actions did not scope the claims to treating and improving, rather assaying for evaluating the effects of specific metabolites in cytokine production in a culture of human monocytes. The Specification does not demonstrate that the claimed microbial strains actually improve symptom of ALS. Applicant hypothesizes that the claimed microbial strains “can” yield these results, but does not demonstrate that the claimed microbial strains actually yield these results. Applicant’s “recognition” is seemingly limited to a hypothesis that has not been reduced to practice and lacks any meaning evidentiary basis in the Specification. Indeed, Applicant’s argument appears to be: it works because the Specification says it could work. Nothing in the Specification demonstrates that administration of, e.g., CT6 compositions actually does anything in vivo, i.e., improvement of at least one symptom of ALS in any subject.
The Specification does not demonstrate that when administered to a subject in need can result in improvement of symptoms of diseases like ALS because, inter alia, the CT6 compositions were never administered to any subject. Further, a single experiment in a generic cell culture cannot reasonably be extrapolated to the improvement of symptoms of ALS in virtually any mammalian subject in need thereof. Changes in cytokine levels in a human monocyte culture does not enable the treatment of ALS. To the contrary, Applicant merely offers a cursory and speculative statement that “[t]he change in cytokine levels using metabolites in monocytes suggests that one or more of these metabolites may be used to modulate, reduce, or reverse inflammation (e.g. including neuroinflammation), which may in turn be used to treat and/or prevent diseases associated with the Vagus Nerve as described herein” (Specification, paragraph 0078, as published).
With regard to the exhibit (submitted August 29, 2024 and resubmitted August 25, 2025), the data was found to be unpersuasive. The data presented in the exhibit presents a scope of data regarding “improved motor function and pathophysiological characteristics of ALS” in SOD1 mice (see pg. 9). According to the data provided, treatment of the mice with the CT6 microbial composition had wide range of effects on various characteristics in the study populations (grip strength, rota rod, hindlimb balance, NMJ innervation, proteosomal function, lysosomal function, etc.). The data shows that there was no statistically significant improvements these characteristics (i.e., symptoms) across male and female mice, and improvements are explicitly characterized as only “suggesting” improvement. The examiner also points Applicant to Vinsant et al. (Brain and Behavior, 3(4):335-350 (2013)) evidences that “numerous preclinical trials have been conducted in the mutant SOD1 mouse models, the results have been disappointing because they did not positively translate to clinical trials” (Abstract), such that the results obtained in ALS mouse models as disclosed in the exhibits cannot be reasonably be extrapolated to virtually any subject. Furthermore, the data in the exhibit has various pages that are blank or missing information (see, e.g., pg. 37, and 58-59). The supplemental experimental data, alone or in combination with the Specification, does not reasonably demonstrate or enable, inter alia, improving one or more of nerve cell damage, nerve ending damage, nerve fiber damage, brain damage, Vagus nerve-associated organ damage, or a combination thereof. As such, the rejection is maintained as set forth above.
Conclusion
NO CLAIMS ALLOWED.
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.
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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