DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/31/2025 has been entered.
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 12/31/2025.
The double patenting rejection of record over claims 1-2, 5-10, 16-19, and 21-28 of copending Application No. 18/604,196 are maintained in view of Applicant’s arguments/amendments in the response filed 12/31/2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/31/2025 was filed after the mailing date of the Final Rejection on 10/01/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 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 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 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 12/31/2025 have been fully considered but they are not persuasive.
On pg. 5-7 of the Remarks, Applicant argues that the claims have been amended to remove the word “preventing,” such that the claims are now directed to improving ALS. Applicant argues that the Office “acknowledged the scope of the claims is enabled by the specification and the experimental data (Exhibit A) previously submitted on August 29, 2024.”
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 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 ALS in any subject. The Specification does not demonstrate that when administered to a subject in need can result in improvement 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 or prevention of ALS in virtually any mammalian subject in need thereof. Changes in cytokine levels in a human monocyte culture does not enable the absolute prevention 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).
Furthermore, the Office’s position regarding the “suggest[ion] of efficacy” does not mean the claims are enabled, nor did the Office acknowledge this. Again, Applicant’s specification only encompasses appreciation of data from human monocyte culture from which Applicant urges would work in vivo. With regard to the exhibit, 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 in a lot of these characteristics across male and female mice, and some improvements are explicitly characterized as only “suggesting” improvement. 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.
Maintained Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 6-10, 22-27, and 149-152 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-10, 16-19, and 21-28 of copending Application No. 18/604,196 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims are drawn to treating a method of treating or preventing any neurodegenerative disease, disorder, or condition, as well as a method of treating amyloid plaques or reducing plaque burden, plaque number, or plaque size in a subject diagnosed with a neurodegenerative disease, disorder, or condition, which would include, e.g., Amyotrophic lateral sclerosis (ALS), the method comprising: administering to a subject in need thereof, e.g., a mammal/human, a composition comprising one or more, e.g., 10, microbial strains or microbial components thereof (claims 1-2, 5-6, 22, 149). The conflicting claims disclose that the one or more microbial strains are from the microbiome of the human subject used to maintain or modulate the microbiome of the subject (claims 7-10).
The conflicting claims disclose that the strains comprise Gluconacetobacter hanseni, Terrisporobacter glycolicus, Coprococcus catus, Lactobacillus plantarum, Veillonella atypica, and Bifidobacterium breve as well as Clostridium butyricum, Paenibacillus sp.,
Acidaminococcus sp., and Bacillus subtilis (claims 1-2, 16-19, 149).
The conflicting claims disclose that the composition is administered topically, orally, subcutaneously, intravenously, intramuscularly, intracerebrally, intrathecally, rectally, opthalmically, intravitreally, or suprachoroidally, and formulated as a syrup, a liquid, a tablet, a troche, a gummy, a capsule, a powder, a gel, a film, an injection, or an eye drop (claims 23-26).
The conflicting claims disclose that each microbial strains are present in the composition at a concentration from 101 to 1015 CFU, e.g., 106 CFU (claims 27-28).
It is noted that instant claim 4 does not recite additional method steps, but, rather, the mechanism by which the claimed composition functions in vivo. As such, since the conflicting claims disclose an identical composition used for an identical purpose, absent evidence to the contrary, the method of the conflicting claims would inherently function by an identical mechanism of action.
As such, the instant and conflicting claims are not patentably distinct. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 12/31/2025 have been fully considered but they are not persuasive.
On pg. 6 of the arguments, Applicant argues that the claims are directed to improving ALS and the claims of ‘196 application are directed to method of treating or preventing Alzheimer’s, Parkinson’s, and methos of treating amyloid plaques, etc. Applicant urges that claim 2 of ‘196 does not cover methods of improving ALS using a composition comprising the microbial strains as claimed.
In response, the examiner disagrees. Copending claim 2 is broadly drawn to “a method of treating or preventing a neurodegenerative disease, disorder, or condition” and copending claim 149 is broadly drawn to a “method of treating amyloid plaques or reducing plaque burden, plaque number, or plaque size in a subject diagnosed with a neurodegenerative disease, disorder, or condition.” As such, the copending claims still encompass ALS (see, e.g., Matrone, Comp. Struct. Biotechnol. J. 21: 923-930 (2023) and Schmidt et al., Acta Neuropathol., 95:117-122 (1998); previously cited in the 09/06/2024 Office Action). As such, the rejections are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGIANA C REGLAS whose telephone number is (571)270-0995. The examiner can normally be reached M-Th: 8:00am-2:00pm.
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672