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 .
Status of the Application
1. 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 Claims 2 and 8-15 are withdrawn from consideration as being drawn to non-elected subject matter.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
2. 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Withdrawn Rejections
3. The 35 U.S.C. 112(b) indefiniteness rejection of claim 4 for no “and,” “or,” or “and/or” separating the listed constituents is withdrawn, since the claim was amended to recite “or.”
Maintained Rejections
Claim Rejections - 35 USC § 103
4. 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.
5. 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.
6. 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), 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, raising the pressure, or a combination of the two, 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 a method of lyophilization of the frozen beads to obtain a lyophilized cellular preparation.
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,” and 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 Henns et al. to lyophilize a probiotic bacterial culture, since Henns et al. teaches this as discussed above.
7. 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 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 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 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 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, 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/maintained 35 U.S.C. 103 rejection of claims 1 and 3-6 over Desjardins and Gillet, as evidenced by “Creative Biolabs: Live Therapeutics,” and in view of Henns et al. Additionally, the applicant traverses the previous/maintained 35 U.S.C. 103 rejection of claim 7 over Desjardins and Gillet, as evidenced by “Creative Biolabs: Live Therapeutics,” and in view of Henns et al, and further in view of Jena et al.
First, the applicant argues that Desjardins and Gillet does not disclose step b of the method of claim 1, i.e. dissolving the gas in the composition, transition of said composition into an area rich in gas molecules, this density being achieved either by (i) either owing to the flow of gas generated by the evaporation of a cryogenic fluid, (ii) or by raising the pressure, (iii) or by the combination of the two phenomena. The examiner respectfully disagrees because Desjardins and Gillet teaches the increase in pressure, where specifically the increase in pressure can be carried out up to a pressure greater than 20 bar (0040), which the claim defines as a method to achieve the area rich in gas molecules/density.
Second, the applicant continues to argue that it is not inherent that there is a transition into an area rich in gas molecules generated by the evaporation of a cryogenic fluid or by the pressure increase. The examiner respectfully disagrees, since the claim defines the density being achieved by raising the pressure (as bolded above).
Third, the applicant argues that this step (step b, argued above in first and second), induces surprising and unexpected improvement in the stability of the cells. The examiner respectfully disagrees. For the reasons discussed above, Desjardins and Gillet teach step b. Additionally, Desjardins and Gillet teach increasing the pressure during cryopreservation to conserve biological materials with a high survival rate (paragraph 16). Desjardins and Gillet continue to teach specific examples (Examples 1 and 3), where they achieve survival rates of 93.7% (Example 1) and 95% (Example 3).
Fourth, the applicant continues to argue that Desjardins and Gillet are silent on a dense zone of gas molecules and the dissolution thereof; however, the examiner respectfully disagrees. Again, as discussed above, the claim defines the dense zone being achieved by the increase in pressure; therefore, it is the examiner’s position that this is an inherent property of the method.
Fifth, the applicant argues there is no dissolution step disclosed in Desjardins and Gillet. Again, the examiner respectfully disagrees. This is essentially the same argument as arguments 1,2, and 4 (above). The examiner maintains that the dissolution step (step b) is achieved by the increase in pressure.
Sixth, the applicant argues that the claimed invention optimizes/uses the dense gas zone to achieve gas dissolution before freezing. The examiner agrees insofar that this is in the claimed method; however, the examiner maintains that Desjardins and Gillet achieve the same step in their method, since the cryogenic method and specifically the increase in pressure is taught.
Last, the applicant argues that the secondary references do not teach step b. The examiner agrees and did not utilize them to teach step b. The examiner maintains that step b is taught in Desjardins and Gillet for the reasons mentioned above (arguments 1-5).
The examiner does not find the arguments presented by the Applicant persuasive, and for these reasons, the rejections of record above apply.
Conclusion
7. All claims are rejected.
THIS ACTION IS MADE FINAL. 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.
8. 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571) 272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656