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 .
DETAILED ACTION
Claims 1, 5, 15-19, 21, and 26-31 are pending.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/29/2026 has been entered.
Claim Objections
Claim 1 is objected to because of the following informalities: “a probiotic bacteria” in line 1 and “consists” in line 2 should be replaced with “probiotic bacteria” and “consist” since bacteria is the plural form of bacterium.
Appropriate correction is required.
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, 5, 21, and 26-31 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.
The instant claims are drawn to a composition comprising probiotic bacteria consisting of at least one evolved bacterial species selected from the group consisting of Streptococcus mitis, Streptococcus oralis, Streptococcus pseudopneumoniae, Streptococcus pneumoniae, Streptococcus infantis, Streptococcus rubneri, Streptococcus australis, Streptococcus dentisani, Streptococcus timonensis, Streptococcus peroris, and combinations thereof, and wherein the at least one evolved bacterial species has a decrease in glucose production an increase in activity of enzymes in glycolysis, pentose phosphate, and/or glycogenesis pathways.
The claims are drawn to a large and variant genus because the genus encompasses any enzyme involved in glycolysis, pentose phosphate, or glycogenesis pathways, as well as any modification, mutation, or compound that result in an increased expression or activity of these enzymes.
The specification discloses collecting saliva samples comprising bacteria and culturing the bacteria in a mixture of glucose and starch for 24 hours, collecting the bacteria and repeating the process two additional times. Genomic analysis was used to identify the bacteria in the sample. The amount of glucose in the supernatant were quantified by colorimetric starch assay.
The claims require the claimed Streptococcus species to have two functions: probiotic and evolved (i.e. exhibiting new functions) and an increased expression or activity of enzymes involved in glycolysis, pentose phosphate pathway, glycogenesis, or combinations thereof. The specification does not describe any conserved genes or components of any of the recited strains that is correlated to the claimed activity of probiotic and evolved bacteria. The specification does not describe any Streptococcus with modified carbohydrate metabolism comprising increased expression or activity of enzymes involved in glycolysis, pentose phosphate pathway, glycogenesis, or combinations thereof.
The prior art Gaspar (Infection and immunity 82.12 (2014): 5099-5109, of record in Office Correspondence mailed on 10/28/2025) reports Streptococcus pneumoniae causes serious diseases in humans, including otitis media, bacteremia, meningitis, and pneumonia (Abstract). Gaspar has disclosed 2 Streptococcus pneumoniae avirulent strains, R6 strain and Streptococcus pneumoniae with absent lactate dehydrogenase LDH (Abstract, FIG 4 legend).
The prior art Puyet (cited in 102 rejection) reports expression of MalA and MalR affect the glucose production, i.e., modify the carbohydrate metabolism of Streptococcus pneumoniae R6 (Table 1).
Prior art Babul (Biochemistry, 32, 4685-4692 (1993)) reports that increasing the amount of aldolase, an enzyme involved in the glycolysis pathway, did not affect the rate of glucose metabolism in E. coli cells (Table 1, page 4687 left column last para.).
The prior art disclosure of 2 species has not established a strong correlation between structure and function, such minimal disclosure in prior art would not lead one skilled in the art to be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. The strains described in Gaspar reference and the proteins described in Puyet are not representative of the entire genus when there is substantial variation within the genome of the strains and within the enzymes of the recited pathways. There may be unpredictability in the functional results obtained from species other than those specifically disclosed in Gaspar and Puyet references. One of ordinary skill in the art would not have recognized that the inventor was in possession of the necessary common attributes or features possessed by the species of the genus in view of the species disclosed by Gaspar and Puyet. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only couple of species within the genus.
Therefore, the inventor was not in possession of the full genus of probiotic and evolved bacterial species selected from Streptococcus mitis, Streptococcus oralis, Streptococcus pseudopneumoniae, Streptococcus pneumoniae, Streptococcus infantis, Streptococcus rubneri, Streptococcus australis, Streptococcus dentisani, Streptococcus timonensis, and Streptococcus peroris, and wherein the evolved bacterial species has a decrease in glucose production and an increase in activity of enzymes in glycolysis, pentose phosphate pathway, and/or glycogenesis pathways.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 21 and 26 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 21 and 26, which depend from claim 1, recite limitations related to the source of the sample but do not further limit the structure of the composition recited in claim 1. MPEP 2111.04 states “Claim scope is not limited by…claim language that does not limit a claim to a particular structure”. Applicant may consider amending the claims to incorporate these limitations at the end of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 5, 21, and 26-31 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception of laws of nature, natural phenomena, and products of nature (a nature-based product) without significantly more.
Claim 1 recites a probiotic composition (Step 1: YES) comprising probiotic bacteria selected from the group consisting of Streptococcus mitis, Streptococcus oralis, Streptococcus pseudopneumoniae, Streptococcus pneumoniae, Streptococcus infantis, Streptococcus rubneri, Streptococcus australis, Streptococcus dentisani, Streptococcus timonensis, and Streptococcus peroris. Claim 1 limits the probiotic bacteria to have a decrease in glucose production and an increase in activity of enzymes in glycolysis, pentose phosphate, and/or glycogenesis pathways. Claim 5 further limits the probiotic bacteria to survive in a culture medium wherein about 100% of carbohydrates are starches. Claims 21 and 26 limit the isolation source of the bacteria to be from a natural source like salvia sample, a tooth swab, a tooth scrapping, a cheek swab, a throat swab, a sputum sample, an endogastric sample, or a fecal sample. Claim 27 limits the amount of the bacteria in the composition. Claims 28-29 recite the composition comprises carriers and buffering agent. Water is a naturally occurring carrier. Milk is a naturally occurring buffering agent as disclosed by Applicant (Specification page 8 line 20). Claims 1, 5, 21, 26, 28-29 recite a natural product. There is no indication in the claim or specification that the probiotic bacteria with decrease in glucose production and an increase in activity of enzymes in glycolysis, pentose phosphate, and/or glycogenesis pathways have markedly different characteristic compared to their naturally occurring counterpart in its natural state. There is no indication that the recited probiotic bacteria have a different structure, form, or genetic modification. The limitations decrease in glucose production and an increase in activity of enzymes in glycolysis, pentose phosphate, and/or glycogenesis pathways do not specify a structural difference between the claimed bacteria and their naturally occurring counterparts in their natural state. There is no indication that the claimed bacteria were not present in the initial sample. Thus, the claimed product lacks markedly different characteristics and is a product of nature (Step 2A prong 1: YES). This judicial exception is not integrated into a practical application because formulating these natural bacteria into a food additive or a fortified food by simply mixing multiple naturally-occurring components is nothing more than an attempt to generally link the product of nature to a particular technological environment (Step 2A prong 2: NO). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception (Step 2B: NO).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 5, 21, and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Puyet (Journal of Biological Chemistry 268.34 (1993): 25402-25408, of record in Office Correspondence mailed on 04/14/2025) as evidenced by Gaspar (Infection and immunity 82.12 (2014): 5099-5109, of record in Office Correspondence mailed on 10/28/2025) and Afzal (PLoS One 10.6 (2015): e0127579).
Regarding claim 1, Puyet teaches that Streptococcus pneumonia strain R6 produces less glucose (nmol of glucose released per min of incubation) compared to other Streptococcus pneumonia strains R6::cat A1 and R6::cat R1, and that R6::cat A1 produces less glucose than strain R6::cat R1 (Table 1) and has a functional MalA and MalR enzymes. As evidenced by Gaspar (FIG 4 legend), Streptococcus pneumonia R6 is avirulent. Puyet teaches Streptococcus pneumonia strains R6::catR1 (malR-) and R6::catA1 (malA-) have chloramphenicol acetyltransferase (cat) gene inserted in malR and malA genes (FIG. 1, page 25404 left column second para.). Thus, it is understood that MalR and MalA encoded by malR and malA genes respectively, are not expressed in these strains. Using the broadest reasonable interpretation, and since the expression of MalR and MalA altered glucose production as taught in Table 1, then MalR and MalA are understood to be involved in glycolysis or glycogenesis pathways. Evidentiary reference Afzal reports MalA is an enzyme (page 3 second para.).
The limitation “wherein the at least one evolved bacterial species is obtained by stress-based directed evolution involving serial passages of a non-evolved bacteria cultured in increasing amounts of starch and selecting for evolved bacteria comprising decreased glucose production relative to non-evolved bacteria” is a product-by-process limitation. There is no evidence that the method of obtaining the strain imparts any additional structural limitation to the composition.
Regarding claim 5, Applicant discloses both evolved and non-evolved bacteria survived in a culture medium wherein at least about 100% of carbohydrates in the culture media are starches (Table 1, page 23 lines 8-9). Thus, this limitation is an inherent characteristic of the evolved or non-evolved Streptococcus pneumonia taught by Puyet.
Regarding claims 21 and 26, the limitations “wherein the at least one evolved bacterial species are bacteria isolated from a microbiota sample” and “wherein the microbiota sample is selected from the group consisting of a salvia sample, a tooth swab, a tooth scrapping, a cheek swab, a throat swab, a sputum sample, an endogastric sample, or a fecal sample” are product-by-process limitations. Determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process (MPEP 2113).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 5, 21, and 26-31 are rejected under 35 U.S.C. 103 as being unpatentable over Puyet (Journal of Biological Chemistry 268.34 (1993): 25402-25408, of record in Office Correspondence mailed on 04/14/2025) in view of Song (Recent Application of Probiotics in Food and Agricultural Science. DOI 10 (2012): 50121), and as evidenced by Gaspar (Infection and immunity 82.12 (2014): 5099-5109, of record in Office Correspondence mailed on 10/28/2025) and Afzal (PLoS One 10.6 (2015): e0127579).
The teachings of Puyet as they pertain to claims 1, 5, 21, and 26 are discussed above and applied herein.
Regarding claims 27-31, Puyet does not teach the probiotic composition comprises between about 103 CFU to about 1015 CFU of the probiotic bacteria, the probiotic composition comprises carriers, excipients, therapeutic agents, or buffering agent, and the composition is food additive.
However, Song teaches bacteria such as Streptococcus species can be formulated into food compositions (Table 3), teaches a concentration of bacteria of 7.5×1010 cfu/ml (page 14 last para.), and teaches yogurt and milk are common vehicles of probiotics (page 9 para. 3.1.3. Cheese) (i.e., carrier and buffer agent).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition taught by Puvet by formulating the strain in a composition comprising 7.5×1010 cfu/ml and yogurt or milk, as suggested by Song. One of ordinary skill in the art would be motivated to do so in order to store and stabilize the bacterium in a composition. Since Puyet teaches a composition of Streptococcus pneumonia and since Song teaches yogurt and milk are common vehicles of bacteria, there is a reasonable expectation of success.
Response to Arguments
Applicant's arguments filed 05/29/2026 have been fully considered but they are not persuasive.
Applicant argues that the inventor was in possession of the full genus of evolved bacteria as claimed in the instant claims.
In response to the argument, Applicant does not provide evidence as to how the inventor was in possession of the full genus of evolved bacteria. The specification does not provide any example of modification of the evolved bacteria. The specification describes taking a sample of saliva which is understood as comprising the listed bacteria as well as other bacteria naturally found in the sample. This sample was subjected to multiple passages. These passages are understood as selection and enrichment step of naturally occurring species found in the sample that have a decrease in glucose production and an increase in activity of enzymes in glycolysis, pentose phosphate, and/or glycogenesis pathways. There is no indication that they species were not present initially and naturally in the sample, and that the serial passages led to evolution instead of their isolation and enrichment from the other bacteria present in the sample. The specification does not show any genetic evolution of these claimed strains compared to the initial sample.
Applicant argues that claim 21 as amended limits the structure of the composition of instant claim 1, as the composition comprises at least one evolved bacterial species limited in instant claim 21 to be bacteria which are isolated from a microbiota sample.
In response to the argument, claims 21 and 26 recite the source of the bacteria. There is no indication that the source of the bacteria imparts any additional structural limitations to the structure already recited in claim 1.
Applicant argues that the mutant strains of Puyet are the bacteria with a modified carbohydrate metabolism and argues that the mutant bacteria have an increased glucose production relative to the unmodified wild-type bacteria. Applicant argues that the claim requires a decreased glucose production relative to non-evolved bacteria, not relative to other evolved bacteria, and that the mutant strains of Puyet have not undergone directed evolution.
In response to the argument, the claims are directed to a product and not a method or process. The limitations of “evolved bacteria” and “non-evolved bacteria” are product by process limitations. Determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process See MPEP 2113. The claims are drawn to a bacteria species selected from the group consisting of Streptococcus mitis, Streptococcus oralis, Streptococcus pseudopneumoniae, Streptococcus pneumoniae, Streptococcus infantis, Streptococcus rubneri, Streptococcus australis, Streptococcus dentisani, Streptococcus timonensis, Streptococcus peroris, and combinations thereof that have an decrease glucose production and an increase in activity of enzymes in glycolysis, pentose phosphate, and/or glycogenesis pathways compared to another bacteria. Puyet teaches Streptococcus pneumoniae R6 strain, Streptococcus pneumoniae R6malA- strain, and Streptococcus pneumoniae R6malR - strain, and teaches R6 strain has decrease in glucose production and has a fully functional MalA and MalR enzymes (i.e., increase in activity of enzymes in glycolysis, pentose phosphate, and/or glycogenesis pathways) as explained above. Therefore, Puyet teaches the limitation of the instant claim.
Conclusion
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/MARY A CRUM/Examiner, Art Unit 1657
/THANE UNDERDAHL/Primary Examiner, Art Unit 1699
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