DETAILED ACTION
Status of claim rejections
The rejection of record under 35 USC 112(a) is maintained/modified in view of Applicant’s arguments/amendments in the response filed 12/11/2025.
The rejection of record under 35 USC 101 is maintained/modified in view of Applicant’s arguments/amendments in the response filed 12/11/2025.
The rejection of record under 35 USC 103 is maintained/modified in view of Applicant’s arguments/amendments in the response filed 12/11/2025.
This Action is Final, as necessitated by amendments.
Maintained/Modified Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 7, 10, 12-16, 18-20, and 57-58 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 written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
Here, the instant claims are broadly drawn to a probiotic Lactobacillus bacterium capable of an adaptive response, e.g., increased expression of transporter genes plus at least one other adaptive response including a) a shorter time to lag phase; b) increased final optical density (OD); c) increased tolerance to pomegranate extract; and/or d) increased expression of glucosidase genes, as compared to a probiotic bacterium not adapted to pomegranate extract, wherein the probiotic bacterium has been pre-cultured in a culture medium comprising a first pomegranate extract and a second pomegranate extract. However, the Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to an adaptive response.
The instant claims encompass an innumerable genus of diverse Lactobacillus probiotic bacteria capable of the adaptive responses as recited above to pomegranate extract. The Specification (¶ 0048, as published) discloses:
As used herein, the term “adaptive response” and/or “adapted response” refers to an response of a bacterium, bacterial strain, bacterial species, and/or bacterial population (e.g., a probiotic bacterium, strain, species, and/or population) resulting from growth in the presence of pomegranate extract (e.g., when grown in a media comprising pomegranate extract—“in the presence of” as used in this context means that the pomegranate is in the media in which the bacteria is grown) that is measurably different in subsequent cultures and educated by (e.g., “primed” by) a first exposure to pomegranate extract (e.g., naïve and/or unprimed, e.g., not previously pre-cultured in the presence of pomegranate extract, e.g., not previously grown in a media comprising pomegranate extract). A bacterium, bacterial strain, bacterial species, and/or bacterial population that is capable of an adaptive response and which has been pre-cultured in media comprising pomegranate may be referred to as a “pomegranate adapted” bacterium, bacterial strain, bacterial species, and/or bacterial population. An adaptive response of a bacterium when it is cultured in media comprising pomegranate extract may include, but is not limited to, adaptive/phenotypic features such as a reduced time to lag phase and/or an increased final optical density (OD). An adaptive response of a bacterium capable of an adaptive response to growth in the presence of pomegranate may be observed following the first culturing (i.e., pre-culture) of the bacterium in media comprising pomegranate and again when the bacterium is further cultured in a medium with or without pomegranate (e.g., either when the bacteria growing in media comprising pomegranate are transferred to new media with or without pomegranate or when fresh media with or without pomegranate is added to the bacteria growing in media comprising pomegranate). The reduced time to lag phase and/or increased final OD is determined as compared to a control (e.g., the same bacterium, bacterial strain, bacterial species, and/or bacterial population cultured in a culture medium comprising pomegranate but that was not pre-cultured in the presence of pomegranate extract). An adaptive response may also comprise altered bacterial gene expression and/or altered pattern of gene expression, including, but not limited, to the induction and/or enhancement of transporter and/or deglycosylation genes, and/or other genes involved in the metabolomechanisms of carbohydrate uptake and phytochemical biotransformation. In some embodiments, an adaptive response may comprise an increased tolerance to the presence of pomegranate extract. In some embodiments, an increased tolerance to pomegranate may comprise, but is not limited to, adaptive/phenotypic features of a pomegranate-adapted bacterium, bacterial strain, bacterial species, and/or bacterial population such as a reduced time to lag phase, an increased final OD, and/or altered gene expression when the pomegranate-adapted bacterium, bacterial strain, bacterial species, and/or bacterial population is further cultured in a medium with pomegranate. Reduced time to lag phase, increased final OD and/or altered gene expression is determined as compared to the same bacterium, bacterial strain, bacterial species, and/or bacterial population when cultured in a medium with pomegranate extract but which was not pre-cultured (e.g., not adapted) in the presence of pomegranate extract.
As such, the instant claims encompass different Lactobacillus subspecies, strains, variants, etc. exhibiting adaptive/phenotypic features such as a reduced time to lag phase and/or an increased final optical density (OD) to preparations of pomegranate extract. It is noted that these “adaptive responses” is what the genus does, not what the genus is.
While the instant claims are drawn to a genus that comprises innumerable Lactobacillus probiotic bacteria, the Specification has only adequately described and successfully reduced to practice select probiotic Lactobacillus species (L. acidophilus, L. gasseri, and L. crispatus) exhibiting unpredictable and inconsistent adaptive responses in the form of gene expression, including up-regulation of transporter genes or glucosidase genes as well as down-regulation of genes encoding “hypothetical proteins” (see e.g., ¶¶ 0117, 0119, as published).
In the absence of a representative number of examples, the Specification must at least describe the structural features that are required for the claimed function, in this case an adaptive response to pomegranate extract. However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to an adaptive response to pomegranate extract. Instead, Applicant merely offers a cursory statement that any Lactobacillus probiotic bacterium having virtually any adaptive response to pomegranate extract will work. Thus, the data disclosed in the specification cannot reasonably be extrapolated to and applied to support possession of the entire claimed genus of pomegranate-adapted Lactobacillus probiotic bacteria as claimed, because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
Response to Arguments
Applicant's arguments filed 12/11/2025 have been fully considered but they are not persuasive.
On pg. 8-9 of the remarks, Applicant argues that the amendments to the claims to recite the transporter genes of dtpT and emrB, Lactobacillus, and are sufficient to overcome the 112(a) rejection. Applicant argues that one of skill in the art would conclude that the disclosure adequately describes the claimed invention because the specification amply describes the structure and functional characteristics of pomegranate adapted probiotic bacterium. Applicant argues that the transporter genes are found across the recited genus that connect the function of adaptive response to the structure of the probiotic composition and points to example 3 of the specification.
In response, the examiner disagrees. The instant claims are broadly drawn to a probiotic Lactobacillus bacterium capable of an adaptive response, e.g., increased expression of transporter genes plus at least one other adaptive response including a) a shorter time to lag phase; b) increased final optical density (OD); c) increased tolerance to pomegranate extract; and/or d) increased expression of glucosidase genes, as compared to a probiotic bacterium not adapted to pomegranate extract, wherein the probiotic bacterium has been pre-cultured in a culture medium comprising a first pomegranate extract and a second pomegranate extract. However, the Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to an adaptive response. Furthermore, as amended, the instant claims encompass different Lactobacillus subspecies, strains, variants, etc. exhibiting adaptive/phenotypic features such as a reduced time to lag phase and/or an increased final optical density (OD) to preparations of pomegranate extract. These “adaptive responses” is what the genus does, not what the genus is. The Specification has only adequately described and successfully reduced to practice select probiotic Lactobacillus species (L. acidophilus, L. gasseri, and L. crispatus) exhibiting unpredictable and inconsistent adaptive responses in the form of gene expression, including up-regulation of transporter genes or glucosidase genes as well as down-regulation of genes encoding “hypothetical proteins” (see e.g., ¶¶ 0117, 0119, as published).
The Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to an adaptive response to pomegranate extract. Instead, Applicant merely offers a cursory statement that any Lactobacillus probiotic bacterium having virtually any adaptive response to pomegranate extract will work. Thus, the rejections are maintained as set forth above.
Maintained/Modified 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 1-2, 7, 10, 12-16, 18-20, and 57-58 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below. See MPEP § 2106 for analysis framework.
The instant claims are drawn to a probiotic composition, i.e., a composition of matter, which is a statutory category of invention (Step 1: YES).
The claimed composition requires a Lactobacillus probiotic bacterium capable of an adaptive response, e.g., naturally occurring human intestinal bacterial species from Lactobacillus and pomegranate extract, which would contain the naturally occurring components of pomegranate (e.g., gallic acid, (free) ellagic acid, glucose, ellagitannins, anthocyanins, etc.). In some embodiments, the claimed composition further requires naturally occurring plant glycosides.
It is noted that instant claim 1 requires the probiotic bacterium to be “pre-cultured in a culture medium comprising pomegranate extract.” This, however, would reasonably encompass a naturally occurring probiotic bacterium cultured in any medium, e.g., water, containing at an amount of about 50 pg/ml to about 2000 pg/ml; and a second pomegranate extract for any de minis amount of time, which, absent evidence to the contrary, would not impart any markedly different characteristics with respect to structure, function, or any other property, to distinguish the claimed probiotic bacterium from its naturally occurring counterpart. Instant claim 1 also requires the bacterium to include transporter genes, such as dtpT, emrB, or homologues thereof.
Altermann et al (Complete genome sequence of the probiotic lactic acid bacterium Lactobacillus acidophilus NCFM. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):3906-12) evidences that, for example, a transporter gene that naturally occurs in the genome of L. acidophilus NCFM (also known as L. acidophilus NCK56); see also UniProt Proteome UP000006381). Applicant’s specification also discloses (see for example, Table 2 and pg. 35, 40-44 of the specification as instantly filed) that SEQ ID NO:1 (the sequence of Altermann) is dtpT (as instantly claimed), a naturally occurring di-tripeptide transporter that is found in L. acidophilus NCFM and that when grown in media containing pomegranate extract, was upregulated in the strain (see pg. 35). This adaptive response and increased expression are, absent evidence to the contrary, inherent, transient responses by the probiotic bacterium to the pomegranate extract. Example 2 of the Specification demonstrates that “when pomegranate extract was removed from the media the adaptive response was lost.” Example 2 of the Specification further discloses that “in the case of L. Acidophilus NCFM, just one transfer to media without pomegranate extract after two transfers to media with pomegranate extract (adaptive response) was sufficient for the bacterial population to lose the adaptive response.” As such, the “adaptive response” recited by the instant claims does not constitute a markedly different characteristic, but, rather, a transient response by naturally occurring bacterium to an external stimulus using its innate biological mechanisms.
Moreover, isolating the naturally occurring components of pomegranate by extraction would not, absent evidence to the contrary, impart any markedly different characteristics with respect to structure, function, or any other property, to distinguish the isolated components of the resulting extract from their naturally occurring counterparts. Likewise, absent evidence to the contrary, formulating naturally occurring probiotic bacterium and pomegranate extract into, e.g., a solution (e.g., water), sachet, beverage (e.g., water), etc., would not result in any markedly different characteristics with respect to structure, function, or any other property, to distinguish the claimed probiotic bacterium and pomegranate extract from their naturally occurring counterparts.
Instant claim 1 also recites that the probiotic bacterium also exhibits at least one other adaptive response in conjunction with the increased transporter gene expression, including a shorter time to lag phase, increased final optical density (OD), increased tolerance to pomegranate extract; and/or increased expression of glucosidase genes, as compared to a probiotic bacterium not adapted to pomegranate extract. As above, this adaptive responses are, absent evidence to the contrary, inherent, transient responses by the probiotic bacterium to the pomegranate extract. Example 2 of the Specification demonstrates that “when pomegranate extract was removed from the media the adaptive response was lost.” Example 2 of the Specification further discloses that “in the case of L. acidophilus NCFM, just one transfer to media without pomegranate extract after two transfers to media with pomegranate extract (adaptive response) was sufficient for the bacterial population to lose the adaptive response.” As such, the “adaptive response” recited by the instant claims does not constitute a markedly different characteristic, but, rather, a transient response by naturally occurring bacterium to an external stimulus using its innate biological mechanisms.
Instant claim 7 recites that the “probiotic bacterium has increased expression of glucosidase genes”. As above, this adaptive responses are, absent evidence to the contrary, inherent, transient responses by the probiotic bacterium to the pomegranate extract (see Example 2 of the Specification as recited above). As such, the “adaptive response” of “increased expression of glucosidase genes” recited by the instant claims does not constitute a markedly different characteristic, but, rather, a transient response by naturally occurring bacterium to an external stimulus using its innate biological mechanisms.
Accordingly, the instant claims recite a natural phenomenon, which is a judicial exception (JE) (Step 2A, Prong 1: YES).
The instant claims are drawn to a probiotic composition, and not a method for using the probiotic composition for any particular prophylaxis or treatment. Moreover, the instant claims do not recite any additional elements beyond the JE besides generic formulations, which would include water. As such, the instant claims do not recite any additional elements that integrate the JE into a practical application (Step 2A, Prong 2: NO).
As discussed above, the instant claims do not recite any additional elements beyond the JE besides generic formulations. As evidenced by Kim et al. (WO 2019/212977), it was well-understood, routine, and conventional at the time of filing to formulate probiotic bacteria and pomegranate extract as tablets, sachets, suppositories, etc. as well as nutritional supplements such as a beverage, yogurt, etc. (¶¶ 0134, 0138-0140). As such, the instant claims do not recite any additional elements that amount to significantly more than the judicial expectation (Step 2B: NO).
In view of the foregoing, the instant claims do not constitute patent eligible subject matter under 35 U.S.C. § 101.
Response to Arguments
Applicant's arguments filed 12/11/2025 have been fully considered but they are not persuasive.
On pg. 10-11 of the remarks, Applicant argues that the bacterium has markedly different characteristics compared to naturally occurring probiotic bacteria and the pomegranate extract itself. Applicant argues that the second pomegranate extract is included in the probiotic and that preculturing imparts markedly different characteristics, because preculturing requires a physical act of transferring the bacterium in a culture medium, which then creates a new and improved composition as it has a shorter time to lag phase, increased final OD, increased tolerance to the extract, and/or decreased expression of glucosidase genes compared to non-adapted bacterium. Applicant further argues that the extracts allow for the phytochemicals of the second extract to be more bioavailable compared to naturally occurring pomegranate.
In response, the examiner disagrees. claim 1 requires the probiotic bacterium to be “pre-cultured in a culture medium comprising pomegranate extract.” This, however, would reasonably encompass a naturally occurring probiotic bacterium cultured in any medium, e.g., water, containing at an amount of about 50 pg/ml to about 2000 pg/ml; and a second pomegranate extract for any de minis amount of time, which, absent evidence to the contrary, would not impart any markedly different characteristics with respect to structure, function, or any other property, to distinguish the claimed probiotic bacterium from its naturally occurring counterpart. Applicant argues that the physical act of transferring the bacteria for a preculturing step imparts markedly different characteristics creating a “new and improved” composition, however, the mere act of isolation or physically transferring a bacterium to a culture does not impart any markedly different characteristics that provide patent eligibility to the bacterium, much like the mere act of physically transferring lettuce from the ground into a basket does not make the lettuce patent eligible.
Furthermore, Example 2 of the Specification demonstrates that “when pomegranate extract was removed from the media the adaptive response was lost.” Example 2 of the Specification further discloses that “in the case of L. acidophilus NCFM, just one transfer to media without pomegranate extract after two transfers to media with pomegranate extract (adaptive response) was sufficient for the bacterial population to lose the adaptive response.” As such, the “adaptive response” recited by the instant claims does not constitute a markedly different characteristic, but, rather, a transient response by naturally occurring bacterium to an external stimulus using its innate biological mechanisms. Whether this adaptive response is shorter time to lag phase, increased final OD, increased tolerance to the extract, or increasing bioavailability, all of these are the result of the bacterium using innate biological mechanisms to create a transient response to the environment. As such, the rejection is maintained as set forth above.
Maintained/Modified Claim Rejections – 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 7, 10, 12-14, 18-20 and 57-58 are rejected under 35 U.S.C. 103 as obvious over Kim et al. (WO 2019/212997, hereinafter “Kim”; prior art of record) in view of Li et al (Anaerobe, 34:164-168 (2015), hereinafter “Li”; prior art of record), and Altermann.
Kim teaches a probiotic composition comprising: 1) a probiotic bacterium from Lactobacillus (e.g., Lactobacillus acidophilus La-14, Lactobacillus rhamnosus, Lactobacillus paracasei, etc., which encompass human intestinal species (see paragraph 0049)); and 2) pomegranate extract (interpreted to be a second pomegranate extract as in claim 1; see paragraphs 0005-0006, and 0049). Since Kim teaches identical probiotic bacteria (as in instant claim 10 and 58), including an identical strain, as recited by the instant claims, the probiotic bacteria taught by Kim would, absent evidence to the contrary, be capable of functional capabilities including shorter time to lag phase, increased final optical density (OD), increased tolerance to pomegranate extract; and/or increased expression of transporter genes and/or glucosidase genes as in instant claim 1. See MPEP § 2112.01(II).
Kim teaches that the probiotic composition further comprises a prebiotic plant glycoside, e.g., punicalagin or ellagic acid (see paragraphs 0041, 0046, 0100). Similar to above, since Kim teaches identical probiotic bacteria and prebiotic plant glycosides, absent evidence to the contrary, the probiotic bacteria taught by Kim are capable of converting the prebiotic plant glycoside into a bioactive aglycone (as in claim 2). Indeed, the probiotic bacteria taught by Kim are used, inter alia, for the biosynthetic preparation of urolithin compounds (as in claim 57) (Abstract).
Kim teaches the probiotic composition comprises, e.g., 108, 109, 1010, or 1011, or 1012 CFU/g of the probiotic bacterium (see claim 5, paragraph 0058; as in instant claim 12). Kim further teaches that the pomegranate extract comprises a polyphenol content of, e.g., “greater than about 55%” or greater than about 60%” gallic acid equivalents, which would encompass the recitation of “about 55% to about 65% gallic acid equivalents” by instant claim 14 (see paragraph 0037). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Kim teaches that the composition is formulated as tablets, sachets, suppositories, etc. (as in claims 18-20; see paragraph 0134). Kim further teaches that the composition is formulated as a nutritional supplement such as a beverage, yogurt, etc. (see paragraphs 0138-0140).
Kim does not explicitly teach that the probiotic bacterium has been pre-cultured in a culture medium comprising a first pomegranate extract. However, it would have been prima facie obvious at the time of filing to pre-culture the probiotic bacterium taught by Kim in pomegranate extract because Li teaches that pomegranate extract stimulates the growth of probiotic bacteria such Lactobacillus in a dose-response manner (Abstract; § 2.4; Table 1). One of ordinary skill in the art would have been motivated to modify Kim in view of Li in order to advantageously enhance growth of the probiotic bacterium thereby increasing the amount of probiotic bacterium available for formulation with a reasonable expectation of success. Furthermore, it also would have been prima facie obvious at the time of filing to pre-culture the probiotic bacterium taught by Kim in pomegranate extract to exhibit features such as shorter time to lag phase, increased final optical density (OD), increased tolerance to pomegranate extract, and/or increased expression of glucosidase genes, because Li teaches that pomegranate extract stimulates the growth of probiotic bacteria such as Bifidobacterium and Lactobacillus in a dose-response manner (Abstract; § 2.4; Table 1).
Kim does not explicitly teach that the amount of the first or second pomegranate extract in the composition is about 50 μg/ml to about 2000 μg/ml (as in claim 1 and 13). However, it would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal concentration of pomegranate extract for use in the composition taught by Kim with a reasonable expectation of success. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Kim does not explicitly teach the genome comprises a transporter gene of dtpT, emrB, and/or a homologue thereof.
However, Altermann et al (Complete genome sequence of the probiotic lactic acid bacterium Lactobacillus acidophilus NCFM. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):3906-12) teacheses a transporter gene of instant SEQ ID NO: 1 (which has 100% identity to the sequence of Altermann; see previous office action) that naturally occurs in the genome of L. acidophilus NCFM (also known as L. acidophilus NCK56 as disclosed in Applicant’s specification; see also UniProt Proteome UP000006381). Applicant’s specification evidences (see for example, Table 2 and pg. 35, 40-44 of the specification as instantly filed) that SEQ ID NO: 1 is dtpT (as instantly claimed), a naturally occurring di-tripeptide transporter that is found in L. acidophilus NCFM and that when grown in media containing pomegranate extract, was upregulated in the strain (see pg. 35). Thus, the adaptive response and increased expression of the transporter gene are, absent evidence to the contrary, inherent, transient responses by the probiotic bacterium to the pomegranate extract, and an inherent result of culturing/adapting the probiotic bacteria taught by Kim in a medium comprising the pomegranate extract taught by Li.
Regarding instant claim 7, as discussed above, given that Kim teaches identical probiotic bacteria, including an identical strain, as recited by the instant claims, increased expression of glucosidase genes would, absent evidence to the contrary, be an inherent result of culturing/adapting the probiotic bacteria taught by Kim in a medium comprising the pomegranate extract taught by Li.
Regarding instant claim 58, Altermann teaches L. acidophilus NCFM.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Second rejection
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable overs Kim, Li, and Altermann as applied to claims 1-2, 7, 10, 12-14, 18-20 and 57-58 above, and further in view of Bialonska et al. (J. Agric. Food Chem., 57:8344-8349 (2009), hereinafter “Bialonska”; prior art of record).
As discussed above, claims 1-2, 7 10, 12-14, and 18-20 were rendered prima facie obvious by the teachings of Kim and Li. The references do not explicitly teach a pomegranate extract comprising gallic acid, ellagic acid, and glucose. However, Bialonska teaches a commercial pomegranate extract comprising ellagitannins (as punicalagins and punicalins), gallic acid, ellagic acid, and glucose (FIG. 1; page 8345, Isolation and Characterization of Tannins). One of ordinary skill in the art would have been free to select from various pomegranate extracts, including those that were advantageously available on the commercial market, for use in the composition taught by Kim and Li with a reasonable expectation of success.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Third rejection
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Kim, Li, and Altermann as applied to claims 1-2, 7, 10, 12-14, 18-20, and 57-58 above, and further in view of Legua et al. (J. Functional Food, 23:628-636 (2016), hereinafter “Legua”; prior art of record).
As discussed above, claims 1-2, 7-8, 10, 12-14, and 18-20 were rendered prima facie obvious by the teachings of Kim and Li . The references do not explicitly teach a pomegranate extract comprising ellagitannins, free ellagic acid, and anthocyanins. However, Legua teaches pomegranate extracts comprising ellagitannins (punicalins, and punicalagins), free ellagic acid, and anthocyanin (Tables 3-4; FIG. 4). One of ordinary skill in the art would have been free to select from various pomegranate extracts, including those that were advantageously characterized by Legua, for use in the composition taught by Kim and Li with a reasonable expectation of success.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary
Response to Arguments
Applicant's arguments filed 12/11/2025 have been fully considered but they are not persuasive.
On pg. 11-13, Applicant argues none of the cited references teach the pomegranate adapted probiotic bacteria. Applicant argues that none of the references teach a pre-cultured probiotic bacterium or increased expression of the recited transporter gene, pointing to Fig. 2A of the specification for support. Applicant argues the adaptive responses shown by the bacterium (shorter time to lag phase, increased final OD, etc). Applicant argues use of inherency in an obviousness rejection and that none of the references explicitly disclose a precultured probiotic and the adaptive responses are not necessarily present. Applicant argues much of the same for the rejections of dependent claims 15 and 16.
In response, the examiner disagrees. Kim, Li, and Altermann, in combination, does teach the probiotic composition as claimed. Kim explicitly teaches probiotic bacteria in a pomegranate extract. Since Kim teaches identical probiotic bacteria (as in instant claim 10 and 58), including an identical strain, as recited by the instant claims, the probiotic bacteria taught by Kim would, absent evidence to the contrary, be capable of functional capabilities including shorter time to lag phase, increased final optical density (OD), increased tolerance to pomegranate extract; and/or increased expression of transporter genes and/or glucosidase genes as in instant claim 1. See MPEP § 2112.01(II). Furthermore, Altermann teaches the transporter gene as claimed, and Li provides teaching, suggestion and motivation to one of ordinary skill to culture the bacteria to stimulate the bacterial growth with a reasonable expectation of success. As the prior art teaches the claimed composition, the features of the bacteria as claimed would be inherent transient properties possessed by the bacteria in the pomegranate extract.
Conclusion
NO CLAIMS ALLOWED.
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.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Srisukchayakul, P. (2017) Effects of acid adaptation on the survival of Lactobacillus plantarum NCMIB 8826 in fruit juices. PhD thesis, University of Reading.
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672