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, 21-24, and 26 are pending. Claims 15-19 are withdrawn.
Response to Amendment
Applicant amended claim 1 and added new limitation “wherein the evolved bacterial species comprises modified carbohydrate metabolism comprising increased expression or activity of enzymes involved in glycolysis, pentose phosphate pathway, glycogenesis, and combinations thereof”.
Applicant amended claims 5 and 21 and added new claim 26.
The rejection of claim 5 under 35 U.S.C. 112(b) is withdrawn in view of the amendment.
The rejection of claims 1, 5 and 21-24 under 35 U.S.C. 101 is withdrawn in view of the amendment.
The rejection of claims 1, 5 and 21-24 under 35 U.S.C. 102(a)(1) is withdrawn in view of the amendment.
Claim Objections
Claim 26 is objected to because of the following informalities: “a endogastric” in line 3 should be replaced by “an endogastric”.
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 and 21-24 remain rejected and claim 26 is 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 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 evolved bacterial species comprises modified carbohydrate metabolism comprising increased expression or activity of enzymes involved in glycolysis, pentose phosphate pathway, glycogenesis, and combinations thereof.
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 comprises modified carbohydrate metabolism comprising increased expression or activity of enzymes involved in glycolysis, pentose phosphate pathway, glycogenesis, and combinations thereof.
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.
Claim 26 is 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.
Claim 26 is indefinite because “selected from” has a narrower range than “comprising”. Applicant may consider amending the claims to recite “-- wherein the microbiota sample is selected from the group consisting of --" in order to obviate the rejection.
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 21-24 remain rejected and claim 26 is 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 21-24 and 26, which depend from claim 1, recite limitations related to the source of the sample and to stress based directed evolution 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 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 § 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, 21-24, 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). 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 21-24 and 26, the limitations “wherein the at least one evolved bacterial species is derived from a microbiota sample”, “wherein the at least one evolved bacterial species is obtained by stress-based directed evolution comprising culturing the non-evolved bacteria in a culture medium comprising at least 30% complex carbohydrates relative to the total amount of carbohydrates”, “wherein the complex carbohydrate is a starch, a fiber, or a combination thereof”, “wherein the complex carbohydrate is a starch”, “wherein the starch is a gelatinized starch” and “wherein the microbiota sample is selected from the group comprising a salvia sample, a tooth swab, a tooth scrapping, a cheek swab, a throat swab, a sputum sample, a 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).
Response to Arguments
Applicant's arguments filed 01/28/2026 have been fully considered but they are not persuasive.
Applicant argues that the specification discloses particular probiotic bacterial
species with specific modifications, and argues the specification's disclosure of modified carbohydrate metabolism, coupled with the well-established biochemical roles of the enzymes within each of the claimed pathways, provides adequate written description support by identifying structural and enzymatic changes that would be recognized as causally linked to the observed phenotype of reduced glucose production.
In response to the argument, as discussed above, 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. Furthermore, any increase in expression of any enzyme involved in the recited pathways does not guarantee a change in glucose metabolism as reported by prior art Babul.
Applicant argues that the amendment to claim 21 further limits the structure of the probiotic composition of claim 1 by specifying the at least one evolved bacterial
species is derived from a microbiota sample.
In response to the argument, there is no indication that the source of the bacteria, whether from saliva or from glycerol stock, affects or changes the structure of the recited bacteria. MPEP 2111.04 states “Claim scope is not limited by…claim language that does not limit a claim to a particular structure”.
Applicant argues claim 1 requires "the at least one evolved bacterial species is obtained by stress-based directed evolution," which is a modification to the genome of the bacteria that is distinct to those taught in Puyet, and argues that Puyet teaches that the genetic modifications are introduced by plasmid transformation, and that Puyet teaches modifications in maltosaccharide metabolism and not in carbohydrate metabolism pathways recited in amended claim 1.
In response to the argument, the limitation “evolved bacterial species is obtained by stress-based directed evolution” is a product-by-process limitation. MPEP 2113 states that even though product-by-process claims are limited by and defined by the process, 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. Furthermore, the claims, as well as the specification, do not limit the genetic modification of the recited bacteria and do not exclude a modification of the genome similar to Puyet’s. Evidentiary reference Afzal reports MalA is an enzyme. Using the broadest reasonable interpretation, since MalA’s expression affected the glucose production, then this enzyme is understood to be involved in the recited pathways.
Applicant argues that the Examiner's comparison of glucose production between mutant strains is an improper comparison because differences in glucose production relative to non-evolved bacteria is not evaluated, and argues that Puyet demonstrates that these modifications in malA and malR yield a significant increase in glucose production relative to the non-modified, wild-type R6 strain of Streptococcus pneumoniae.
In response to the argument, Puyet teaches R6 strain, R6malA- and R6malR-, and teaches the glucose production of these strains as explained above. Applicant is interpreting R6malA- and R6malR- as the evolved species and R6 as the non-evolved. However, using the broadest reasonable interpretation, one of ordinary skill in the art would also interpret R6malA- and R6malR- as non-evolved and R6 strain as evolved. The claim does not limit the genome or the genetic modification of the evolved and non-evolved strains.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MARY A CRUM whose telephone number is (571)272-1661. The examiner can normally be reached M-F 8:00-5:00 CT with alternate Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, LOUISE W HUMPHREY can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY A CRUM/ Examiner, Art Unit 1657
/THANE UNDERDAHL/ Primary Examiner, Art Unit 1699