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
The amendment filed 09/12/2025 has been entered. Claims 26-43 are pending and under examination.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/12/2025 has been entered.
Claim Objections
Claim 2and 42 are objected to because of the following informalities: the claims contain grammatical errors.
In claim 28, the word “the” should be added before “dietary compounds”.
In claim 29, the word “the” should be added before “prebiotics”.
In claim 34, the word “bacteria” should be amended to “bacterial”.
In claim 42, the word “metabolics” should be amended to “metabolomics”.
Appropriate correction is required.
Response to Arguments
With respect to the rejection of claims 26-43 under 35 USC 103, Applicant's arguments filed 09/12/2025 have been fully considered but they are not persuasive. Applicant arguments are in view of the amendments made to independent claims 26 and 42. Said amendments are unclear and have introduced new rejections under 35 USC 112(b), and under the broadest reasonable interpretation, are disclosed by the prior art teachings.
Applicant argues that Shah does not teach having a first channel containing cells of a host patient, and specifically microbiota or gut cells of the host, whereas the second channel comprises no cells of a host or patient, but probiotics sourced differently, being perfused with a medium of dietary compounds.
The Examiner respectfully disagrees, as Shah specifically teaches using a microfluidics-based model that allows for co-culture of human and microbial cells (Abstract). Shah teaches that the microfluidics-based device contains a top microbial microchamber above an epithelial cell microchamber, wherein the two microchambers (i.e., two channels) are separated by a nanoporous (i.e., semi-permeable) membrane (Figure 1a). Shah teaches that the human epithelial cells were isolated from the human intestine (i.e., gut cells) (Page 2, Results and Discussion, Paragraph 2).
Zenhausern teaches a microfluidics device that may be used to study host-microbial interactions and the effects of commercially available prebiotics on microbiota (Paragraph bridging pages 6 to 7).
Although Shah teaches that the microbial cells are commensal Lactobacillus rhamnosus cells (Abstract), Shah does not teach that they were isolated from the host/patient in which the gut cells were isolated from. Moreover, the instant claim does not recite that the probiotics are sourced differently, but only recites: wherein a second channel…supports at least one probiotics culture not containing cells from a host. Therefore, it is interpreted that the claim means that the second channel containing probiotics does not contain the host gut/microbiota cells that are in the first channel.
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 26-43 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.
Claim 26 recites a method but only recites characteristics of the microfluidic cell culture device and implies perfusing the second channel with prebiotics. Therefore, it is unclear what active steps are required by the method.
Claim 26 also recites: at least one probiotics culture not containing cells of a host. It is unclear if this limitation means that the probiotic bacteria are not commensal to the organism from which the microbiota/gut cells are obtained, or if the claim means that the probiotics culture does not contain the host microbiota/gut cells of the first channel.
Claims 27-38 are also rejected as they depend from claim 26.
Claims 27 is indefinite because it is a “use” claim that attempts to claim a process without setting forth any steps involved in the process. MPEP § 2173.05(q) states that attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Claim 38 is considered a product-by-process claim but does not recite additional method steps that materially impart structural limitations of the claimed product. Therefore, it is unclear what ingredient(s) or structures are required for the claimed synbiotic regimen. Claim 39 is dependent upon claim 38 and only recites an intended use; hence, claim 39 is also rejected.
Claim 41 recites: a “bare” in line 2 and a “substance tablet” in line 4. These terms are not defined in the instant specification and are not well known in the art or widely used by one of ordinary skill in the art. Therefore, it is unclear what these claim terms mean and encompass.
Claim 42(iii) recites a probiotics culture, not comprising cells of a host. It is unclear if this limitation means that the probiotic bacteria are not commensal to the organism from which the microbiota/gut cells are obtained, or if the claim means that the probiotics culture does not contain the host microbiota/gut cells of the first channel.
Claim 42(v) recites: and other molecular analysis techniques at the end of the sentence. It is unclear what are considered other suitable molecular analysis techniques that are required in the claimed invention to analyze the interactions between the host microbiota/gut cells, prebiotics, and probiotics.
Claim 43 is also rejected as it depends from claim 42.
Therefore, one of ordinary skill in the art would not be able to ascertain the metes and bounds of the claimed invention in claims 26-43.
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.
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.
It is interpreted that the claim means that the second channel containing probiotics does not contain the host gut/microbiota cells that are in the first channel.
Claims 26-28 and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Shah et al. (A microfluidics-based in vitro model of the gastrointestinal human-microbe interface, 2016) in view of Zenhausern et al. (WO 2016/189142 A1).
Regarding claim 26, Shah teaches a method of investigating host-microbe molecular interactions using a microfluidics-based model that allows for co-culture of human and microbial cells (Abstract). Shah teaches that the microfluidics-based device contains a top microbial microchamber above an epithelial cell microchamber, wherein the two microchambers (i.e., channels) are separated by a nanoporous (i.e., semi-permeable) membrane (Figure 1a). Shah teaches that the human epithelial cells were isolated from the human intestine (i.e., gut cells) (Page 2, Results and Discussion, Paragraph 2). Shah teaches that each microchamber has a dedicated inlet and outlet for inoculation of cells as well as for the precise control of physiochemical parameters through the perfusion of laminar streams of dedicated culture medium (Page 2, Results and Discussion, Paragraph 1).
Shah does not teach perfusion of the microbes with a medium of dietary compounds.
However, Zenhausern teaches a cell culture apparatus capable of emulating a part or parts of the gastrointestinal tract and methods for using the same (Abstract). Zenhausern teaches that the apparatus may be used to study host-microbial interactions and the effects of commercially available prebiotics, which are considered dietary compounds, on microbiota (Paragraph bridging pages 6 to 7) or to test the efficacy of pre-, pro-, and synbiotics in the modulation of human gastrointestinal microbiota (Paragraph bridging pages 6 to 7).
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have perfused the top microchannel of Shah containing the probiotic with a prebiotic dietary compound as taught by Zenhausern. One of ordinary skill in the art would have been motivated to do so because Zenhausern teaches that a microfluidic device comprising gastrointestinal tract epithelial cells and microbes can be used to study the effects of prebiotics on host microbiota. One of ordinary skill in the art would have had a reasonable expectation of success because Shah and Zenhausern are in the same field of endeavor of microfluidic devices for the study of host-microbe interactions.
Regarding claims 27-28, Zenhausern teaches that the apparatus may be used to study host-microbial interactions and the effects of commercially available pre- and/or probiotics on microbiota (Paragraph bridging pages 6 to 7) or to test the efficacy of pre-, pro-, and synbiotics in the modulation of human gastrointestinal microbiota (Paragraph bridging pages 6 to 7). Shah teaches that the microfluidic device (HuMiX) facilitates host-microbe molecular interactions (Abstract).
Regarding claim 36 and 37, as stated, Shah teaches that the intestinal epithelial cells are human, i.e., mammalian (Abstract).
Claim 38 is considered a product-by-process claim. See MPEP 2113.I, which states: "[E]ven 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." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Zenhausern teaches that the device of the instant invention may be used to test the efficacy of synbiotics to modulate the human GI microbiota (paragraph spanning pages 6 and 7), therefore, because Zenhausern teaches synbiotics, the limitation of claim 38, i.e., a synbiotic regimen, is considered to be met.
Claims 29-35 and 39-43 are rejected under 35 U.S.C. 103 as being unpatentable over Shah et al., 2016 (A microfluidics-based in vitro model of the gastrointestinal human-microbe interface) and Zenhausern et al. (WO 2016/189142 A1) as applied to claim 26 above, and further in view of Dutta et al. (US 2018/0110800 A1), previously cited.
As stated above, the combination of Shah and Zenhausern teach the use of a microfluidics cell culture device comprising a top channel containing microbes and a bottom channel containing intestinal epithelial cells. The combination of Shah and Zenhausern teaches that microfluidics cell culture devices can be used to study the effects of prebiotics on the host microbiota.
Zenhausern and Shah do not teach the use of synbiotics to treat human gut microbiome-linked diseases, specific prebiotic compounds, or compounds secreted by probiotics.
However, Dutta teaches a combination of pro- and prebiotics (i.e. a synbiotic regimen) for the treatment of dysbiosis (Page 2, Paragraph 0015).
Regarding claims 29 and 30, Dutta teaches that prebiotics are non-digestible fiber (Page 4, Paragraph 0043). Dutta teaches that exemplary prebiotic compounds include, but are not limited to, fructans (i.e., fructooligosaccharides) or trans-galactooligosaccharides (Page 4, Paragraph 0043).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to utilize the microfluidic devices and methods of using as taught by Shah and Zenshausern, to generate a synbiotic regimen as taught by Dutta. One of ordinary skill in the art would have been motivated to do so because Zenhausern teaches that the apparatus may be used to test the efficacy of pre-, pro-, and synbiotics in the modulation of human gastrointestinal microbiota (Page 7, Paragraph 1). One of ordinary skill in the art would have had a reasonable expectation of success because the teachings of Shah, Zenhausern and Dutta are in the same field of endeavor of gut cell-microbe interaction studies.
Regarding claim 31, Dutta teaches that metabolites produced by microbes, such as fermentation products, have been implicated in regulating host health (Page 1, Paragraph 003). Dutta teaches microbial metabolites that influence GI health include short-chain fatty acids (Page 2, Paragraph 0010) and that anaerobic fermentation of polysaccharides results in the production of three major short-chain fatty acids, including acetate (Page 2, Paragraph 0011).
Regarding claims 32 and 33, Dutta teaches gut bacteria as probiotics (Page 2, Paragraph 0018).
Regarding claim 34, Shah teaches the use of Lactobacillus species (Abstract)
Regarding claim 35, Shah teaches the use of Lactobacillus rhamnosus (Abstract).
Regarding claim 39, Dutta teaches that the synbiotic regimen can be used to treat GI diseases associated with dysbiosis (Page 2, Paragraph 0016).
Regarding claims 40 and 41, Dutta teaches that the synbiotic composition is formulated as an enteric coated capsule for oral administration (Claim 5), i.e., a pharmaceutical composition.
Regarding claim 42, Shah teaches a method of investigating host-microbe molecular interactions using a microfluidics-based model that allows for co-culture of human and microbial cells (Abstract). Shah teaches that the microfluidics-based device contains a top microbial microchamber above an epithelial cell microchamber, wherein the two microchambers (i.e., channels) are separated by a nanoporous (i.e., semi-permeable) membrane (Figure 1a). Shah teaches that the human epithelial cells were isolated from the human intestine (i.e., gut cells) (Page 2, Results and Discussion, Paragraph 2). Shah teaches that each microchamber has a dedicated inlet and outlet for inoculation of cells as well as for the precise control of physiochemical parameters through the perfusion of laminar streams of dedicated culture medium (Page 2, Results and Discussion, Paragraph 1). Shah teaches methods of analyzing the host-microbe interactions (p. 10, col. 2, para. 3). Shah teaches fluorescence microscopic analysis of the co-cultured cells (p. 13, col. 1, para. 2). Shah teaches the use of transcriptomics (Figure 5).
Shah does not teach perfusion of dietary compounds or teach that prebiotics contain dietary fiber.
Zenhausern teaches a cell culture apparatus capable of emulating a part or parts of the gastrointestinal tract and methods for using the same (Abstract). Zenhausern teaches that the apparatus may be used to study host-microbial interactions and the effects of commercially available prebiotics, which are considered dietary compounds, on microbiota (Paragraph bridging pages 6 to 7) or to test the efficacy of pre-, pro-, and synbiotics in the modulation of human gastrointestinal microbiota (Paragraph bridging pages 6 to 7).
Zenhausern does not teach that prebiotics contain dietary fiber.
However, Dutta teaches that prebiotics are non-digestible fiber (Page 4, Paragraph 0043)
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have perfused the top microchannel of Shah containing the probiotic with a prebiotic as taught by Zenhausern containing dietary fiber, as taught by Dutta. One of ordinary skill in the art would have been motivated to do so because Zenhausern teaches that a microfluidic device comprising gastrointestinal tract epithelial cells and microbes can be used to study the effects of prebiotics on host microbiota. One of ordinary skill in the art would have had a reasonable expectation of success because Shah, Zenhausern, and Dutta are in the same field of endeavor of gut cell-microbe interaction studies.
Regarding claim 43, Shah teaches the use of human gastrointestinal cells, i.e., gut cells (Abstract).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657