DETAILED ACTION
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 .
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02 May 2026 has been entered.
Status of the Application
2. Claims 1-15 are pending and subject to examination on the merits. Claims 2 and 8-15 are withdrawn from consideration as being drawn to non-elected subject matter. Claims 1 and 3-7 are currently under examination.
Priority
3. Acknowledgement is made of applicant’s claim for foreign priority based on an application filed in FR (FR1913627 on 02 December 2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Rejections
4. The rejection of claims 1 and 3-6 as obvious over the teachings of Desjardins and Gillet, 2018, WO 2018/138461 A1—cited on the Information Disclosure Statement filed 26 May 2022; the English translation provided herein as a PDF), as evidenced by “Creative Biolabs: Live Therapeutics” (“Creative Biolabs: Live Therapeutics,” 2025, downloaded 03 September 2025 from < https://live-biotherapeutic.creative-biolabs.com/lactobacillus-delbrueckii.htm#:~:text=Lactobacillus%20delbrueckii%20(L.,delbrueckii%20subsp.> --provided previously as a PDF), and in view of Henns et al (Henns et al., 2014, US8906668B2—cited previously) is withdrawn in view of the amendments to claim 1, which now specifically recites “generated by the evaporation of a cryogenic fluid or (ii) by the combination of evaporation of the cryogenic fluid and by raising the pressure.” Desjardins and Gillet, as evidenced by “Creative Biolabs: Live Therapeutics,” and in view of Henns et al. do not teach formation of a dense gaseous region by evaporation or evaporation and the rise in pressure. Said rejection has been withdrawn in view of the modified rejection below.
5. The rejection of claim 7 as obvious over the teachings of Desjardins and Gillet, 2018, WO 2018/138461 A1—cited on the Information Disclosure Statement filed 26 May 2022; the English translation provided herein as a PDF), as evidenced by “Creative Biolabs: Live Therapeutics” (“Creative Biolabs: Live Therapeutics,” 2025, downloaded 03 September 2025 from < https://live-biotherapeutic.creative-biolabs.com/lactobacillus-delbrueckii.htm#:~:text=Lactobacillus%20delbrueckii%20(L.,delbrueckii%20subsp.> --provided previously as a PDF), and in view of Henns et al (Henns et al., 2014, US8906668B2—cited previously), and further in view of Jena et al (Jena et al., 2013, Microbiology and Immunology—cited previously) is withdrawn in view of the amendments to claim 1, which now specifically recites “generated by the evaporation of a cryogenic fluid or (ii) by the combination of evaporation of the cryogenic fluid and by raising the pressure.” Desjardins and Gillet, as evidenced by “Creative Biolabs: Live Therapeutics,” in view of Henns et al., and further in view of Jena et al. do not teach formation of a dense gaseous region by evaporation or evaporation and the rise in pressure. Said rejection has been withdrawn in view of the modified rejection below.
Claim Rejections - 35 USC § 103
6. 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.
7. 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.
8. Claims 1 and 3-6 are rejected under 35 U.S.C. 103 as being unpatentable over Desjardins and Gillet, 2018, WO 2018/138461 A1—cited on the Information Disclosure Statement filed 26 May 2022; the English translation provided herein as a PDF), as evidenced by “Creative Biolabs: Live Therapeutics” (“Creative Biolabs: Live Therapeutics,” 2025, downloaded 03 September 2025 from < https://live-biotherapeutic.creative-biolabs.com/lactobacillus-delbrueckii.htm#:~:text=Lactobacillus%20delbrueckii%20(L.,delbrueckii%20subsp.> --provided previously as a PDF), in view of “CryoGearUSA” (“CryoGearUSA,” 2001, downloaded 22 July 2026 from < https://www.cryogearusa.com/ln2-dewars-and-storage-freezers/> as a PDF—cited herein), and in view of Henns et al (Henns et al., 2014, US8906668B2—cited previously). Regarding claim 1, drawn to a method of lyophilization of a cellular composition, where the freezing step is carried out by cryogenics under pressure, said method comprising the steps of: a) providing a cellular composition comprising cells in an aqueous medium, b) dissolving a gas in said composition by passage of said composition through a dense zone of gas by evaporation of a cryogenic fluid or a combination of evaporation of the cryogenic fluid and raising the pressure, cryogenizing the gas-rich composition obtained in step b) at a pressure that allows said gas to be kept dissolved for obtaining frozen beads, and d) lyophilization of frozen beads to obtain a lyophilized cellular preparation, Desjardins and Gillet teaches a high-pressure cryogenic process for cooling biological material, with solidification of the biological material by a cryogenic fluid, at a pressure of at least 10 bar (abstract) and that the biological material can be a unicellular microorganism (0034). Specifically, Desjardins and Gillet teach a cryogenic fluid being a gas or supercritical state (paragraphs 0035-0036), where the pressure must be greater than 20 bar (paragraph 0040), and beads are obtained at the end of the cryogenic process (0068). Regarding claim 3, drawn to nitrogen, Desjardins and Gillet continue to teach the pressurization of nitrogen (Example 4). Regarding claims 4-5, drawn to a lactic acid bacteria for probiotic interest in animals and humans (claim 5), Desjardins and Gillet teach that among the unicellular microorganisms, mention may be made of yeasts (eg Saccharomyces such as S. cerevisiae and S. boulardii), bacteria (eg Lactobacillus such as L. delbrueckii, in particular L. bulgaricus, and Streptococci such as S. thermophilus) and certain algae (eg diatoms) (paragraph 0034). Specifically, L. delbrueckii is a probiotic and can be isolated from yogurt, cheese, or faecal microbiota of piglets, as evidenced by “Creative Biolabs: Live Therapeutics” (p. 1 paragraphs 1-2; p. 4, boxes at the end for ordering). Regarding claim 6, drawn to the cellular composition not containing a cryoprotectant, Desjardins and Gillet teach that the object of the present invention is to allow the conservation of biological materials with a high survival rate and in particular without the use of assets cryoprotectants (paragraph 0016).
Dejardins and Gillet, as evidenced by “Creative Biolabs: Live Therapeutics,” do not teach the evaporation of the cryogenic liquid to create a dense gas layer or a method of lyophilization of the frozen beads to obtain a lyophilized cellular preparation.
“CryoGearUSA” teaches the continuous boiling of liquid nitrogen (utilized as a cryogenic liquid), where said liquid expands as vapor at a rate of 696:1 (vapor to liquid) and produces gas continuously (p. 1, paragraph 1). Said vapor is therefore a gas that forms above the liquid nitrogen and is able to be vented from the loose fitting top or pressure release valves if necessary (See diagrams).
Henns et al. teaches culturing a strain to reach sufficient biomass and subsequent preservation for banking by cryopreservation treatment by freezing a liquid at ultra-low temperatures. Subsequently, it is dried preserved by removing the water from the culture by sublimination for freeze drying (Column 25, lines 61- Column 26, lines 7). Henns et al. further teaches that the removal of water improves long-term bacterial composition storage stability above temperatures above cryogenic (Column 26, lines 8-9).
Therefore, it 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 combine the teachings of Dejardins and Gillet, as evidenced by “Creative Biolabs: Live Therapeutics,” in view of “CryoGearUSA”, and in view of Henns et al. to store bacterial compositions above cryogenic storage temperatures for long-term storage as taught by Henns et al. One would be motivated to combine these teachings to arrive at the instant claims to lyophilize a probiotic bacterial composition as a defined composition to decrease susceptibility to infection and/or facilitate restoration of a healthy gut microbiota as taught by Henns et al (Column 2, lines 27-29). Additionally, one would be motivated to lyophilize a cryogenically preserved probiotic bacterial strain, since fecal transplantation has shown promise but is not FDA approved and likely will not due to its inability to be standardized and characterized according to regulatory requirements (Column 2, lines 23-26). There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Dejardins and Gillet, as evidenced by “Creative Biolabs: Live Therapeutics,” and “CryoGearUSA”, and Henns et al. to lyophilize a probiotic bacterial culture, since Henns et al. teaches this as discussed above.
9. Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Desjardins and Gillet, 2018, WO 2018/138461 A1—cited on the Information Disclosure Statement filed 26 May 2022; the English translation provided previously as a PDF), as evidenced by “Creative Biolabs: Live Therapeutics” (“Creative Biolabs: Live Therapeutics,” 2025, downloaded 03 September 2025 from < https://live-biotherapeutic.creative-biolabs.com/lactobacillus-delbrueckii.htm#:~:text=Lactobacillus%20delbrueckii%20(L.,delbrueckii%20subsp.> --provided previously as a PDF), in view of “CryoGearUSA” (“CryoGearUSA,” 2001, downloaded 22 July 2026 from < https://www.cryogearusa.com/ln2-dewars-and-storage-freezers/> as a PDF—cited herein), in view of Henns et al (Henns et al., 2014, US8906668B2—cited previously), and further in view of Jena et al., 2013, Microbiology and Immunology—cited previously).
The teachings of Desjardins and Gillet as evidenced by “Creative Biolabs: Live Therapeutics, and in view of “CryoGearUSA”, and in view of Henns et al. are discussed above and incorporated into the instant rejection.
Desjardins and Gillet as evidenced by “Creative Biolabs: Live Therapeutics, and in view of “CryoGearUSA,” and in view of Henns et al. do not specifically teach the cellular composition as a sample of fecal microbiota.
Jena et al. teaches the isolation and subsequent characterization of lactobacilli isolates from the feces of male Wistar rats, where L. helveticus PJ4 and L. plantarum PJ7 are ideal probiotic candidates (abstract). Jena et al. continues to teach that fecal samples were collected and lactobacilli were isolated, where typical colonies were subjected to morphological and biochemical characteristics, and selected isolates were then frozen for probiotic evaluation (p. 408, 2nd column, 2nd-3rd paragraph).
Therefore, it 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 combine the teachings of Desjardins and Gillet as evidenced by “Creative Biolabs: Live Therapeutics, and in view of “CryoGearUSA”, and in view of Henns et al. with Jena et al. to lyophilize a cellular composition consisting of lactic acid microbiota from feces to further characterize its probiotic potential as taught by Jena et al. One would be motivated to combine these teachings to arrive at the instant claims to identify the lactobacilli flora of laboratory animals that have potential probiotic properties and to understand the ecological habitat of these hosts as taught by Jena et al (p. 408, 1st full paragraph). Further, one would be motivated to combine these teachings to lyophilize a probiotic bacterial composition as a defined composition to decrease susceptibility to infection and/or facilitate restoration of a healthy gut microbiota as taught by Henns et al (Column 2, lines 27-29). There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Desjardins and Gillet as evidenced by “Creative Biolabs: Live Therapeutics,, in view of “CryoGearUSA,” and in view of Henns et al. with Jena et al. to lyophilize a probiotic bacterial strain isolated from feces microbiota, since Henns et al. teaches the lyophilization of bacterial compositions, as taught above.
Applicant’s Arguments and Examiner’s Rebuttal:
The applicant traverses the previous obviousness rejections of record of Claims 1 and 3-6 as being unpatentable over Desjardins and Gillet (WO 2018/138461), as evidenced by Creative Biolabs: Live Therapeutics," 2025, in view of Henn et al. (US Patent 8,906,668) and claim 7 as being unpatentable over Desjardins and Gillet (WO 2018/138461), as evidenced by Creative Biolabs: Live Therapeutics," 2025, in view of Henn et al. (US Patent 8,906,668) and further in view of Jena et al., 2013. The applicant has amended claim 1 to include the limitation of “generated by the evaporation of a cryogenic fluid or (ii) by the combination of evaporation of the cryogenic fluid and by raising the pressure.” This new claim limitation has been addressed in the new rejection found above.
First the Applicant argues that there is no motivation to combine the art or expectation of success, and further, that both are found in the Applicant’s application not in the prior art teachings. The examiner respectfully disagrees. The motivation to combine was taught in the prior art and cited in the instant rejection as well as the previous, and is “One would be motivated to combine these teachings to arrive at the instant claims to lyophilize a probiotic bacterial composition as a defined composition to decrease susceptibility to infection and/or facilitate restoration of a healthy gut microbiota as taught by Henns et al (Column 2, lines 27-29). Additionally, one would be motivated to lyophilize a cryogenically preserved probiotic bacterial strain, since fecal transplantation has shown promise but is not FDA approved and likely will not due to its inability to be standardized and characterized according to regulatory requirements (Column 2, lines 23-26).” Regarding the expectation of success, the examiner also provided a statement of reasonable expectation of success in both the instant rejection and the previous rejection of record, where the action states, “There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Dejardins and Gillet, as evidenced by “Creative Biolabs: Live Therapeutics,” and “CryoGearUSA”, and Henns et al. to lyophilize a probiotic bacterial culture, since Henns et al. teaches this as discussed above.” Additionally, the metric is a “reasonable expectation of success” not an absolute expectation of success.
Second, the applicant argues that Desjardins and Gillet are silent in reference to the dense layer of gas being formed by evaporation. The examiner agrees and included the new teaching from “CryoGearUSA” to reach this claim limitation.
Third, the applicant argues that the composition in Desjardins and Gillet would not pass through the dense gas without being cryogenized first. The examiner respectfully disagrees. While Desjardins and Gillet do not show the specific vessel that is utilized, CryoGearUSA does show a number of liquid nitrogen dewars that show that inserting a composition into the liquid nitrogen would require passage through a layer of gas collected in the neck/above the liquid nitrogen, since the liquid nitrogen is under constant boiling, which continuously releases vapor that either needs to be vented or released via a pressure release valve (As taught in the above instant rejection).
Fourth, the applicant re-iterates that Desjardins and Gillet do not teach the formation of a dense gaseous zone by evaporation. The examiner agrees and introduced “CryoGearUSA” to reach this claim limitation, as discussed in argument two, above.
Fifth, the applicant argues that Henns et al. does not teach the passage of the composition through the dense zone of gas and subsequent cryogenization. The examiner agrees insofar that Henns et al. was not utilized as prior art to teach these limitations. Henns et al. was utilized to teach the lyophilization of frozen beads instead. Rather, Desjardins and Gillet was utilized to teach the cryogenization method of passing the composition through the dense layer of gas and contacting the cryogenic liquid. And further, since this is an obviousness type rejection, Henns et al. is not required to teach all of the limitations of the claim.
Sixth, the applicant continues to argue the lack of motivation and expectation of success of the previous rejection of record. The examiner respectfully disagrees for the same reasons discussed above in argument one.
Seventh, the applicant argues that there are surprising and unexpected improvements to the stability of the cells when combining cryogenization with lyophilization in this manner. However, the claims have been obviated by the prior arts teachings, and therefore, it would be an inherent feature of the method to provide stability to the cells, which would not be unexpected or surprising.
The examiner does not find the arguments presented by the Applicant persuasive, and for these reasons, the rejections of record above apply.
Conclusion
10. All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
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/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656
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