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 .
Election/Restrictions
Applicant’s election without traverse of Invention 1 (a formulated composition, claims 1-14) in the reply filed on 15 Dec 2025 is acknowledged. Applicant’s election of the species of animal subjects in the reply filed on 23 April 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 11-12 and 15-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (claims 11-12) and invention (claims 15-21), there being no allowable generic or linking claim. Election was made without traverse in the replies filed on 15 Dec 2025 and 23 April 2026.
Claim Status
The original claim set filed 4 Jan 2024 is acknowledged. Claims 1-21 are currently pending. Claims 11-12 and 15-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (claims 11-12) and invention (claims 15-21), there being no allowable generic or linking claim. Election was made without traverse in the replies filed on 15 Dec 2025 and 23 April 2026. Claims 1-10 and 13-14 will be examined on the merits herein.
Priority
The instant application claims priority to provisional application 63/437,240 (filed 5 Jan 2023). What follows is the examiner’s claim-by-claim analysis of effective filing date for the claims currently under examination. If the applicant disagrees with this examiner’s determination of effective filing date for any claim, the applicant may identify text within the prior applications that provides support the claimed language.
The provisional application does not disclose a formulated composition for treating or preventing epithelial fungal infection and correcting dysbiosis in or on a subject, as in claims 1-10 and 13-14. The provisional application also does not disclose the genus of compositions comprising an effective dose of yeast cells containing a plurality of genes encoding functions of tolerance to a high temperature, tolerance to high and low pH, adherence to cells of the subject, and biosynthesis of amino acid alcohols, as in claims 1-10 and 13-14.
Therefore, the provisional application does not fully support the claimed subject matter. In this action, the effective filing date used for searching all claims is 4 Jan 2024.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 4 Jan 2024 and 21 Jul 2025 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner. Signed copies of these statements are attached with this action.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
The drawings are objected to because they cannot be interpreted in a black-and-white format. It is noted that a petition for color drawings was filed 4 Jan 2024; however, this petition was dismissed on 19 April 2024.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 13 is objected to because of the following informalities: clear typographical error. “Clostridium difficile” should be spelled with two fs. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10 and 13-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the claim recites the limitation “a plurality of genes encoding functions of tolerance to a high temperature, tolerance to high and low pH, adherence to cells of the subject, and biosynthesis of amino acid alcohols”. In the claim, the genes are defined solely based on “encoding” certain functions. But, genes encode a protein rather than a cellular function, and the claimed functions do not recite specific encoded proteins. See MPEP 2173.05(g): “ the use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971). For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008) (noting that the Supreme Court explained that a vice of functional claiming occurs "when the inventor is painstaking when he recites what has already been seen, and then uses conveniently functional language at the exact point of novelty") (quoting General Elec. Co. v. Wabash Appliance Corp., 304 U.S. 364, 371 (1938));” In this case, the limitations describing the gene’s functions are indefinite because the claims and specification do not define how to determine which genes fulfill the function. The specification provides examples of genes for each function in [0034], but does not provide a clear-cut way in which one of ordinary skill in the art at the time of filing could determine whether a gene not listed in the specification meets the functional limitation or not. As a result, the bounds of the claim cannot be determined.
Also, the terms “high temperature” and “high and low pH” are relative terms which render the claim indefinite. The terms “high” and “low” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As a result, one of ordinary skill in the art at the time of filing would not be appraised of what temperatures and pH the yeast must be capable of tolerating. Claims 2-10 and 13-14 are also rejected because they depend from claim 1 and do not obviate these grounds of rejection.
Regarding claim 2, the claim recites “at least one species selected from Saccharomyceacea and Issatchenkia families of yeasts.” Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The meaning of the term “family” cannot be interpreted, but is clearly not the accepted meaning of the term to refer to the level of taxonomic relatedness. The term “Saccharomyceacea” is not a taxonomic family; instead, the family comprising Saccharomyces is “Saccharomycetaceae”. It is unclear what yeasts are included within this grouping that does not have an accepted definition. Also, “Issatchenkia” is a genus name rather than a family name. The term “family” is indefinite because the specification does not clearly redefine the term and the term “Saccharomyceacea” is indefinite because the specification does not clearly define the term. In the interest of compact prosecution, this claim will be interpreted as including the Saccharomyces and Issatchenkia genera that are discussed in the specification.
Regarding claims 3-6, the claims recite “a first portion of the genes” (claim 3), “a second portion of the genes” (claim 4), “the third portion of the genes” (claim 5), and “a fourth portion of the genes” (claim 6). There is insufficient antecedent basis for the limitation “portion of the genes” in the claims. Claim 1 recites “a plurality of genes” instead, and this difference makes it unclear whether these limitations are limiting the functions recited in claim 1 or whether they are defining additional sets of genes that must be present in the yeast cell. Claims 8-10 and 13-14 are also rejected because they depend from claim 5 and do not obviate this grounds of rejection. In the interest of compact prosecution, in this action these claims will be interpreted as limiting the functions recited in claim 1 rather than requiring additional genes.
Regarding claim 6, the claim recites “at least one amino acid alcohol including tryptonol and phenylethanol”. The grouping of alternative amino acid alcohols is indefinite because the grouping is not a closed list (“including” encompasses other, non-listed options) and it is unclear what other alternatives are intended to be encompassed by the claim. See MPEP 2173.05(h) and In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022).
Regarding claims 6-7, the claims have a clear typographical error, but the intended correction is not apparent. The chemical “tryptonol” does not appear to exist. A Google search shows that there are multiple different potential chemicals and spellings for the misspelled term (see below). Therefore, the claim scope cannot be determined by one of ordinary skill in the art at the time of filing. If amending the claims, please be mindful to not introduce new matter.
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Google search results, search performed 9 June 2026.
Regarding claim 10, it recites the limitation "the fungal infection". There is insufficient antecedent basis for this limitation in the claim. Claim 1 recites “epithelial fungal infection” instead, and the phrasing of claim 10 does not make it clear whether the “epithelial” limitation from claim 1 is present in claim 10 or whether claim 10 is improperly broadening claim 1.
Regarding claim 13, the claim recites the limitation “the gastrointestinal dysbiosis”. There is insufficient antecedent basis for this limitation in the claim in parent claims 1 or 5; claim 1 only recites the generic “dysbiosis”. It is possible this claim was intended to depend from claim 10.
Also, claim 13 states “the gastrointestinal dysbiosis is at least one selected from symptoms of: colitis, Crohn’s disease, Clostridium dificile infection, Alzheimer’s disease, attention deficit disorder, depression, and diarrhea.” Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “dysbiosis” appears to be used by the claim to mean “symptoms of a disease correlated with changes in a microbiome,” while the accepted meaning is “alterations in gut microbiota composition and function… The most typical features of dysbiosis are a decrease in the diversity of the microbiota, a loss of beneficial microbiota, or an overgrowth of harmful microbiota.” (Hrncir 2022; Abstract; PTO-892) The term is indefinite because the specification does not clearly redefine the term.
Regarding claim 14, the claim recites the limitation “the epidermal dysbiosis”. There is insufficient antecedent basis for this limitation in the claim in parent claims 1 or 5; claim 1 only recites the generic “dysbiosis”.
Claim Rejections - 35 USC § 112(a)
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 1-10 and 13-14 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 formulated composition for treating or preventing Candida infections comprising yeast with genes disclosed in the specification, does not reasonably provide enablement for a formulated composition for treating or preventing epithelial fungal infection and correcting dysbiosis in or on a subject, especially when the gastrointestinal dysbiosis is at least one selected from symptoms of: colitis, Crohn’s disease, Clostridium difficile infection, Alzheimer’s disease, attention deficit disorder, depression, and diarrhea or the epidermal dysbiosis is tinea or dermatophytosis and the fungus is at least one genus selected from Epidermophyton, Microsporum, Malassezia and Trichophyton, using yeast who are defined solely by containing genes defined solely by their function. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include: (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, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01. Although all factors were considered, the Wands factors that were most relevant for this decision are discussed in detail below.
The breadth of the claims: Claim 1 recites “A formulated composition for treating or preventing epithelial fungal infection and correcting dysbiosis in or on a subject, comprising an effective dose of yeast cells containing a plurality of genes encoding functions of tolerance to a high temperature, tolerance to high and low pH, adherence to cells of the subject, and biosynthesis of amino acid alcohols.” Claim 2 limits the yeast cells to being certain genera, interpreted as including Saccharomyces and Issatchenkia. Claims 4-6 narrow the gene functions from claim 1. Claim 7 recites that the composition further comprises “at least one of tryptonol and phenylethanol.” Claims 8-9 recite that the subject is specific animals (including humans) and the effective dose is in certain ranges of cells. The specification does not define any additional features for the composition that are required for the composition to be suitable for administration to different animals, so claims 8-9 any composition is interpreted as being suitable for administration to the claimed animals unless the reference states otherwise. Claim 10 recites that the fungal infection is at least one selected from a species of Candida, Histoplasma, Blastomyces, Coccioides, Aspergillus, and Neurospora, and the composition is formulated as at least one selected from: a capsule or tablet for treatment of gastrointestinal dysbiosis; and a suppository, a cream, a douche rinse, and a gel for treatment of vaginal or vulval dysbiosis.
Thus, the claimed compositions encompass a broad range of yeasts, defined solely by the functions of their genes, and a broad range of formulations defined by the preamble’s functional intended use.
The amount of direction provided by the inventor and the existence of working examples: With regard to the “genes encoding functions of tolerance to a high temperature, tolerance to high and low pH, adherence to cells of the subject, and biosynthesis of amino acid alcohols” (claim 1) and the narrower versions of these functions in claims 3-6, the specification describes examples of genes known to the art to have these functions in [0034]. The working example showed percent identity comparisons between known probiotic-related proteins and the genomes of S. cerevisiae KTP and S. boulardii unique28 strains [0038, Figure 2]. The specification does not disclose how to identify additional “genes encoding functions of tolerance to a high temperature, tolerance to high and low pH, adherence to cells of the subject, and biosynthesis of amino acid alcohols.” The specification does not disclose additional yeasts that comprise the art-known genes.
With regard to the intended uses of the composition, including “composition for treating or preventing epithelial fungal infection and correcting dysbiosis in or on a subject” (claim 1), “the gastrointestinal dysbiosis is at least one selected from symptoms of: colitis, Crohn’s disease, Clostridium dificile infection, Alzheimer’s disease, attention deficit disorder, depression, and diarrhea” (claim 13), and “the epidermal dysbiosis is tinea or dermatophytosis and the fungus is at least one genus selected from Epidermophyton, Microsporum, Malassezia and Trichophyton” (claim 14). The specification states that probiotic yeast are known to inhibit pathogens like Candida albicans [0006], and cites to prior studies that demonstrated Saccharomyces cerevisiae KTP, and Issatchenkia/ Pichia occidentalis ApC antagonize Candida species [0021, studies discussed in more detail in “state of the prior art” section below]. The specification asserts that “a fungal infection caused by one or more of Candida, Histoplasma, Blastomyces, Coccioides, Aspergillus, and Neurospora may be effectively treated … [and] configurations herein may be effective against gastrointestinal dysbiosis including symptoms of: colitis, Crohn's disease, Clostridium dificile infection, Alzheimer's disease, attention deficit disorder, depression, and diarrhea” [0026-0027]. However the specification does not disclose what specific “configuration” of the composition is effective in these ways, and does not explain the scientific reasoning behind the conclusion of efficacy, other than generally stating that “the gut and the nervous system have a complex bidirectional communication” [0024]. The specification describes prophetic experiments that could be used to test:
neuronal connections between the gut and brain [0031],
effects of the Saccharomyces cerevisiae KTP and Issatchenkia/ Pichia occidentalis ApC on gut dysbiosis [0032]
effects of the Saccharomyces cerevisiae KTP and Issatchenkia/ Pichia occidentalis ApC on the vaginal microbiome, using vaginal cell lines and mouse models [0032], [0045-0050]
evaluation of the safety profile of the yeasts S. cerevisiae and I. occidentalis using a mouse model [0051]
However, these prophetic experiments do not demonstrate that Saccharomyces cerevisiae KTP and Pichia occidentalis ApC (or any other yeast comprising similar genes) are capable of use to achieve a health outcome. Finally, the specification discloses that after characterizing whether a yeast has genes encoding the functions of claim 1, “It should then be determined that the isolate candidate can remediate the dysbiosis disorders by containing the genes” [0053]. In other words, being capable of use to treat the claimed diseases is an additional functional limitation for the composition rather than being an inherent result of the yeasts’ genes.
The working example performed an in vitro experiment showing that S. cerevisiae and I. occidentalis (strains not disclosed) prevent adhesion of C. albicans to the vaginal cell line VK2/E6E7 [0055-0056, Figures 7-8] and that S. cerevisiae and I. occidentalis (strains not disclosed) attach to vaginal cells [0057-0058, Figures 9-10]. The specification does not provide any working examples related to preventing infection by non-Candida species or related to treating non-infection diseases.
The state of the prior art and the level of predictability in the art: Lohith and Anu-Appaiah (2018; made of record in IDS filed 4 Jan 2024) teach that Saccharomyces cerevisiae KTP and Issatchenkia occidentalis ApC are tolerant to pH 2.5 (Abstract, Figure 1A), bile juice media at pH 8.0 (pg. 1025 par. bridging cols., Figure 2), and high temperatures of 28 and 37°C (Figure 1B). The strains are able to adhere to Caco-2 colorectal epithelial cells (Figure 3, pg. 1026 col. 2 par. 3) and inhibit adhesion of Candida albicans (Figure 5, pg. 1027 par. bridging cols.). Kunyeit et al. (2019; made of record in IDS filed 4 Jan 2024) teach further experiments on the same two yeast strains and teaches “In vivo studies using Caenorhabditis elegans suggest that exposure to probiotic yeasts protects nematodes from infection with non-albicans Candida strains compared to worms that were not exposed to the probiotic yeasts. Furthermore, application of probiotic yeasts postinfection with non-albicans Candida alleviated pathogenic colonization of the nematode gut.” (Abstract). Kunyeit et al. (2021; PTO-892) teach further experiments on the same two yeast strains (pg. 10 par. 5) and teaches that they “inhibit virulence traits of C. albicans, [and] protect the model host Caenorhabditis elegans from C. albicans infection” (Abstract) and teaches that wild-type S. cerevisiae comprises the genes ARO8 and ARO9 by producing a mutant that lacks those genes and is unable to produce aromatic alcohols (pg. 7 par. 3) and showed that both yeast strains produce the aromatic alcohols phenylethanol and tryptophol (Table 1, pg. 7 par. 2). Therefore, the art teaches that the Saccharomyces cerevisiae KTP and Issatchenkia occidentalis ApC must contain the plurality of genes responsible for these functions, and that compositions comprising these yeasts are capable of preventing and treating Candida infections (both C. albicans and other species) in C. elegans. The art is silent on whether these strains can prevent or treat other types of infections such as C. difficile (claim 13), tinea or dermatophytosis, Epidermophyton, Microsporum, Malassezia and Trichophyton (claim 14), and whether these strains can prevent or treat non-infection conditions such as dysbiosis (claim 1), and colitis, Crohn’s disease, Alzheimer’s disease, attention deficit disorder, depression, and diarrhea (claim 13).
The art at the time of filing makes clear that one of ordinary skill in the art at the time of filing believes that claims of in vivo disease outcomes should be supported by experimentation, and that in vitro studies of safety are insufficient to demonstrate in vivo disease outcomes. The FAO/WHO Joint Guidelines for the Evaluation of Probiotics in Food (2002; PTO-892) teach “In vitro tests are critical to assess the safety of probiotic microbes (see Section 3.3). In addition, in vitro tests are useful to gain knowledge of strains and the mechanism of the probiotic effect. However, it was noted that the currently available tests are not fully adequate to predict the functionality of probiotic microorganisms in the human body. … Probiotics for human use will require substantiation of efficacy with human trials” (pg. 4). The European Food Safety Authority Guidance related to health claims related to dietary products (2015; PTO-892) teaches “The scientific evidence for the substantiation of health claims related to defence against pathogens in the GI tract can be obtained from human intervention studies showing an effect on clinical outcomes related to GI infections, for example incidence, severity and/or duration of diarrhoeal episodes” (pg. 13 section 3.5.2) and teaches that claims related to reducing disease risk need to demonstrate that the treatment both reduces the risk factor and also reduces the disease risk (pg. 15 section 4.1). Vinderola et al. (2017; PTO-892) teaches “the correlation of in vitro results with in vivo performance remains obscure” (Abstract). It is noted that the scope of claims under examination is different from the scope of claims that the FAO/WHO or EFSA would be examining (notably, the instant claimed subjects are not limited to humans); and the Office is not requiring human trials to support the claimed method. Instead, these references are cited to show that there is wide agreement in the art at the time of filing that in vitro results do not necessarily correlate with or predict an in vivo outcome of treating or preventing disease, and that additional evidence is needed to show that the probiotic has the desired in vivo effect.
The quantity of experimentation needed to make or use the invention and the nature of the invention: The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success and without undue experimentation. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, and practice the claimed method without first making a substantial inventive contribution.
The nature of the invention is a formulated composition defined by being capable of the function “treating or preventing epithelial fungal infection and correcting dysbiosis in or on a subject”. The specification only provides an in vitro assay showing that S. cerevisiae and I. occidentalis prevents and treats C. albicans attachment to cells in vitro, and the art at the time of filing corroborates that Saccharomyces cerevisiae KTP and Issatchenkia occidentalis ApC are able to prevent and treat Candida infections (both C. albicans and other species) in C. elegans. However, the art also makes clear that in silico genomic analysis and experimentation with one specific type of disease is not enough to predict in vivo results for other diseases, and the art also makes clear that the full breadth of disease results cannot be predicted based on other art at the time of filing. Therefore, a person having ordinary skill in the art would have to perform multiple further in vivo experiments, in human clinical trials or in animal models, in a representative number of epithelial fungal infections and dysbiosis conditions (including the conditions of claim 13 that are not generally considered to be a dysbiosis) in order to identify what yeasts and formulations are capable of being used with a reasonable expectation of success to both treat and prevent diseases and conditions representative of the scope claimed, with a low level of predictability of success.
Also, nature of the invention is a composition comprising a yeast cell defined solely by its gene functions (“tolerance to a high temperature, tolerance to high and low pH, adherence to cells of the subject, and biosynthesis of amino acid alcohols”). The specification gives examples of genes that could have those functions [0034], but neither the claim nor specification define how to identify additional genes with the claimed functions. The specification is not enabling for the full scope claimed because, like In re Hyatt, the claim covers every conceivable structure (means) for achieving the stated property (result) while the specification discloses at most only those known to the inventor. See MPEP 2164.08(a). Therefore, to make the composition as claimed with a reasonable expectation of success, a person having ordinary skill in the art would also have to perform multiple further experiments to determine which genes are responsible for the claimed functions in a representative number of yeasts, and would also have to sequence the genomes of a representative number of yeasts in order to determine whether or not they contain any of these newly identified genes.
The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine’ within the art, and constitutes undue further experimentation in order to make the product with a reasonable expectation of successfully treating or preventing epithelial fungal infection and correcting dysbiosis in or on a subject comprising an effective dose of yeast cells containing a plurality of genes encoding functions of tolerance to a high temperature, tolerance to high and low pH, adherence to cells of the subject, and biosynthesis of amino acid alcohols. Instead, the specification only enables a product capable of treating or preventing Candida infections comprising yeast with genes disclosed in the specification. Therefore, claims 1-10 and 13-14 are rejected under 35 U.S.C. §112(a) or 35 U.S.C. §112, first paragraph, for failing to meet the enablement requirement across the full scope that is claimed.
Claims 1-10 and 13-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163 states:
An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate").
The breadth of the claims is discussed in full in the enablement rejection above, but briefly, the claimed compositions encompass a broad range of yeasts, defined solely by the functions of their genes, and a broad range of formulations defined by the preamble’s functional intended use.
The teachings of the specification and the art are described in full in the enablement rejection. Briefly, the specification teaches in vitro experiments showing that undisclosed strains of Saccharomyces cerevisiae and Issatchenkia occidentalis impair Candida albicans adhesion to a vaginal cell line [0055-0056, Figures 7-8], and showed that the genomes of S. cerevisiae KTP and S. boulardii unique28 strains comprise known probiotic-related proteins [0038, Figure 2] that are examples of genes that have the claimed “functions of tolerance to a high temperature, tolerance to high and low pH, adherence to cells of the subject, and biosynthesis of amino acid alcohols”. The specification also describes some prophetic experiments and formulation information, but does not explain which formulations and yeasts are capable of use “for treating or preventing epithelial fungal infection and correcting dysbiosis in or on a subject”. The art teaches that Saccharomyces cerevisiae KTP and Issatchenkia occidentalis ApC are known to have all the properties described in the list of gene functions, and that the strains antagonize both C. albicans and other Candida species in a C. elegans model.
Therefore, the claim describes a genus (“formulated composition”) defined by its function in vivo (“for treating or preventing epithelial fungal infection and correcting dysbiosis in or on a subject”), but there is no established correlation between the formulation and the outcome in either the specification or the art at the time of filing, commensurate in scope with what is claimed. The composition disclosed in the specification and art, a composition comprising Saccharomyces cerevisiae KTP and Issatchenkia occidentalis ApC, has not been shown to treat a representative number of diseases within the genus because it has only been shown to antagonize Candida.
Therefore, the claim also describes a genus (“a plurality of genes”) defined by its function (“encoding functions of tolerance to a high temperature, tolerance to high and low pH, adherence to cells of the subject, and biosynthesis of amino acid alcohols”), but there is not an established correlation between the function and the gene responsible because many different genes are disclosed as having the functions and additional genes might have the functions [0034]. Also, the specification does not disclose a representative number of genes with each function because additional yeasts and genes are being isolated from nature and characterized, but what is disclosed in the specification and art only reflects the current state of the art rather than new discoveries.
When evaluating the specification in the context of the prior art at the time of filing, one having ordinary skill in the art at the time of filing would have concluded that the specification demonstrated possession of a formulated composition for treating or preventing Candida infections comprising yeast with genes disclosed in the specification, but has not demonstrated possession of a formulated composition for treating or preventing epithelial fungal infection and correcting dysbiosis in or on a subject, especially when the gastrointestinal dysbiosis is at least one selected from symptoms of: colitis, Crohn’s disease, Clostridium difficile infection, Alzheimer’s disease, attention deficit disorder, depression, and diarrhea or the epidermal dysbiosis is tinea or dermatophytosis and the fungus is at least one genus selected from Epidermophyton, Microsporum, Malassezia and Trichophyton, using yeast who are defined solely by containing genes defined solely by their function. Therefore, claims 1-10 and 13-14 are rejected for failing to demonstrate possession of the claimed invention.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
Regarding claims 1-6, claim 1 recites “A formulated composition for treating or preventing epithelial fungal infection and correcting dysbiosis in or on a subject, comprising an effective dose of yeast cells containing a plurality of genes encoding functions of tolerance to a high temperature, tolerance to high and low pH, adherence to cells of the subject, and biosynthesis of amino acid alcohols.” Claim 2 limits the yeast cells to being certain genera, interpreted as including Saccharomyces and Issatchenkia. Claims 4-6 narrow the gene functions from claim 1. (Step 1: YES, a composition of matter).
The specification teaches “two yeasts isolated from fermented beverages … The first strain, Saccharomyces cerevisiae KTP, isolated from palm toddy, and the second strain, Pichia occidentalis ApC, isolated from fermented apple juice” [0021], and that the second strain was also referred to as Issatchenkia occidentalis [0036]. Therefore, these strains are natural products because they were isolated from nature rather than being created or modified by human experimentation.
The specification teaches that S. cerevisiae KTP has genes associated with heat stress (i.e. “tolerance to a high temperature”), acidic adaptation and alkaline adaptation (“tolerance to high and low pH”), flocculation/adherence, and aromatic alcohol production (“biosynthesis of amino acid alcohols”, note ARO8 and ARO9 are present in the strain and those genes produce tryptophol and phenylethanol per [0034]) [Figure 2]. The specification also teaches that both S. cerevisiae and I. occidentalis can adhere to vaginal epithelial cells [0057, Figures 9-10] and prevent Candida albicans adhesion to the epithelial cells [0056, Figures 7-8], so they must have the genes required for the functions.
Also, Lohith and Anu-Appaiah (2018; made of record in IDS filed 4 Jan 2024) teach that Saccharomyces cerevisiae KTP and Issatchenkia occidentalis ApC are tolerant to pH 2.5 (Abstract, Figure 1A), bile juice media at pH 8.0 (pg. 1025 par. bridging cols., Figure 2), and high temperatures of 28 and 37°C (Figure 1B). The strains are able to adhere to Caco-2 colorectal epithelial cells (Figure 3, pg. 1026 col. 2 par. 3) and inhibit adhesion of Candida albicans (Figure 5, pg. 1027 par. bridging cols.). Kunyeit et al. (2019; made of record in IDS filed 4 Jan 2024) teach further experiments on the same two yeast strains and teaches “In vivo studies using Caenorhabditis elegans suggest that exposure to probiotic yeasts protects nematodes from infection with non-albicans Candida strains compared to worms that were not exposed to the probiotic yeasts. Furthermore, application of probiotic yeasts postinfection with non-albicans Candida alleviated pathogenic colonization of the nematode gut.” (Abstract). Kunyeit et al. (2021; PTO-892) teach further experiments on the same two yeast strains (pg. 10 par. 5) and teaches that they “inhibit virulence traits of C. albicans, [and] protect the model host Caenorhabditis elegans from C. albicans infection” (Abstract) and teaches that wild-type S. cerevisiae comprises the genes ARO8 and ARO9 by producing a mutant that lacks those genes and is unable to produce aromatic alcohols (pg. 7 par. 3) and showed that both yeast strains produce the aromatic alcohols phenylethanol and tryptophol (Table 1, pg. 7 par. 2). Therefore, the art teaches that the Saccharomyces cerevisiae KTP and Issatchenkia occidentalis ApC must contain the plurality of genes responsible for these functions.
The claims are drawn to a formulated composition rather than the natural yeast strains per se, but the formulated composition does not require any components other than the yeast. In Ass’n for Molecular Pathology v. Myriad Genetics, Inc., the Supreme Court made clear that the process of isolating a natural product does not necessarily make the product patent-eligible; the isolated product must be markedly different properties from the natural product. See MPEP 2106.04(c). In this case, the isolated yeast formulated composition does not have any markedly different properties from the natural version of the strain before isolation. So, the formulated composition directed to a natural product. (Step 2A Prong 1: YES).
This judicial exception is not integrated into a practical application because there are no additional elements claimed other than the natural yeast (Step 2A Prong 2: NO). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed other than the natural yeast (Step 2B: NO).
Regarding claim 7, the claim depends from claim 1 and recites that the composition further comprises “at least one of tryptonol and phenylethanol.” However, as discussed for claim 1, Kunyeit et al. (2021; PTO-892) teaches that the natural yeasts produce phenylethanol. So the composition comprising the yeast would also comprise this phenylethanol, and this claim is directed to a natural product for the same reasons as claim 1.
Regarding claims 8-9, the claim depends from claim 1 and recites that the subject is specific animals (including humans) and the effective dose is in certain ranges of cells. The specification does not define any additional features for the composition that are required for the composition to be suitable for administration to different animals. So as stated in the rejection of claim 1, the formulated composition does not require any components other than the yeast. In Ass’n for Molecular Pathology v. Myriad Genetics, Inc., the Supreme Court made clear that the process of isolating a natural product does not necessarily make the product patent-eligible; the isolated product must have markedly different properties from the natural product. See MPEP 2106.04(c). In this case, the isolated yeast formulated composition does not have any markedly different properties from the natural version of the strain before isolation. So, these claims are directed to a natural product for the same reasons as claim 1.
Regarding claim 10, the claim depends from claim 1 and recites that the fungal infection is at least one selected from a species of Candida, Histoplasma, Blastomyces, Coccioides, Aspergillus, and Neurospora, and the composition is formulated as at least one selected from: a capsule or tablet for treatment of gastrointestinal dysbiosis; and a suppository, a cream, a douche rinse, and a gel for treatment of vaginal or vulval dysbiosis. As discussed above for claim 1, the natural Saccharomyces cerevisiae KTP and Issatchenkia occidentalis ApC strains are capable of preventing or treating a Candida fungal infection. Also, the formulation requires nothing more than yeast in water (“rinse”). (Step 1: YES, composition of matter). As the yeast and water are both natural products and combining them does not change the properties of either product, the formulated composition is not markedly different from the natural products. (Step 2A Prong 1: YES).
This judicial exception is not integrated into a practical application because there are no additional elements claimed other than the natural yeast (Step 2A Prong 2: NO). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed other than the natural yeast (Step 2B: NO).
Claim Rejections - 35 USC § 102
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 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.
Claims 1-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kunyeit et al. (2021; hereafter Kunyeit; PTO-892) as evidenced by Lohith and Anu-Appaiah (2018; hereafter Lohith; made of record in IDS filed 4 Jan 2024).
Regarding claims 1-6, Kunyeit teaches a composition comprising 108 cells/ml of Saccharomyces cerevisiae KTP or Issatchenkia occidentalis ApC (see claim 2), and teaches that it is effective to antagonize adhesion of Candida albicans in the C. elegans gut (i.e. treating epithelial fungal infection) (Abstract, pg. 2 par. 4, pg. 8 par. 2, pg. 10 par. 2 and 5). Kunyeit teaches “The nematode gut faithfully recapitulates a mammalian intestine” (Abstract) (see subjects in claims 5, 8, 9). Kunyeit teaches the strains produce the aromatic alcohol phenylethanol (Table 1 on pg. 7), therefore the yeast “[contain] containing a plurality of genes encoding functions of … biosynthesis of amino acid alcohols” (see claim 1) and “enzymes for biosynthesis of at least one amino acid alcohol including tryptonol and phenylethanol” (see claim 6).
MPEP 2112 states: “"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).” MPEP 2112.01 states: “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). … "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Lohith provides evidence that Saccharomyces cerevisiae KTP and Issatchenkia occidentalis ApC are tolerant to pH 2.5 (Abstract, Figure 1A), bile juice media at pH 8.0 (pg. 1025 par. bridging cols., Figure 2), and high temperatures of 28 and 37°C (Figure 1B). The strains are able to adhere to Caco-2 colorectal epithelial cells (Figure 3, pg. 1026 col. 2 par. 3) and inhibit adhesion of Candida albicans (Figure 5, pg. 1027 par. bridging cols.). Therefore, Lohith provides evidence that the composition and yeast taught by Kunyeit “contain[s] a plurality of genes encoding functions of tolerance to a high temperature, tolerance to high and low pH, [and] adherence to cells of the subject” (see claim 1), “tolerance to environmental temperatures in a range of 25° C to 42° C” (see claim 3), “tolerance to a low pH in a range of pH 2 to pH 4, and a high pH of pH 8 to a pH of 9” (see claim 4), and “adherence to epithelial cells selected from … gastrointestinal tract” (see claim 5), because the yeasts have the functional properties that result from the genes.
Regarding claim 7, Kunyeit teaches “Yeast produces aromatic alcohols such as tryptophol and phenylethanol in a cell density-dependent manner (7). They produce 140 to 200mM tryptophol and phenylethanol (36) at a cell density of >107/ml.” (pg. 10 par. 2). Therefore, the composition further comprises phenylethanol.
Regarding claims 8-9, the Kunyeit composition teaches 108 cells/ml, which is in the disclosed ranges. There is no evidence of record that the composition is not capable of being administered to the claimed species. Also, Kunyeit teaches “The nematode gut faithfully recapitulates a mammalian intestine” (Abstract) (see subjects in claims 5, 8, 9).
Regarding claim 10, the fungal infection that is treated is Candida. Specifically, Kunyeit teaches a liquid composition comprising yeast in YPD media (pg. 10 par. 5). This composition is capable of being used as a rinse, absent evidence to the contrary.
Conclusion
No claims are allowed.
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/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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