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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-10 and 13-18 in the reply filed on 10/02/2025 is acknowledged. The traversal is on the ground(s) that: “The Examiner has not demonstrated that Patzold teaches the claimed feature or that the feature fails to provide a technical contribution across the groups. ” This is not found persuasive because: the same technical feature between the method claims and product claims is a synthetic mixed culture of at least 8 different bacterial strains resembling a skin microbiome. Patzold teaches the same claimed feature, i.e. complex mixtures of bacterial strains (Title) comprising 2-10 bacterial strains of skin microbiome such as different Propionibacterium acnes strains (p. 2, lines 18-19).
The requirement is still deemed proper and is therefore made FINAL.
Claims 11, 12, 19 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/02/2025.
Applicant's election with traverse of species Malassezia in claim 15 in the reply filed on 10/02/2025 is acknowledged. The traversal is on the ground(s) that: “The Examiner has not provided evidence or cited any reference establishing that the genera listed in claim 15 are patentably distinct within the context of the claimed screening method. ” This is found persuasive and species election is withdrawn.
Claims 1-10 and 13-18 (claim set filed 05/31/2023) are examined on the merits herein.
Priority
This application is a 371 of PCT/EP2021/083112 filed 11/26/2021 Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). based on EPO 20210929.4 filed 12/01/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/31/2023, 07/11/2023 and 08/04/2025 comply with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
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 1-10 and 13-18 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 1 recites: “resembling a skin microbiome” and claim 5 recites “resembling the skin microbiome”. The term “resembling a (the) skin microbiome” is a relative term which renders claims 1 and 5 indefinite. The term “resembling a (the) skin microbiome” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification defines that term as: “The term "resembling a skin microbiome" in context with the instant invention is to be understood, that the synthetic mixed culture's properties are very similar to a natural occurring microbiome present on skin, although its complexity in terms of number of different microorganisms is reduced compared to the natural occurring microbiome present on the respective skin” (p. 4, lines 21-24). However, the term “very similar” is also a relative term since the degree of similarity is not provided. It is not clear, for instance, how many species of natural skin microbiome present in the mixed culture is considered “resembling” or “very similar” or if species not present in natural skin microbiome but having similar features can be present. The scope and boundaries of claims 1 and 5 are not certain making claims 1 and 5 indefinite.
Additionally, claim 1 recites: “deducing the bioactivity of the compound by deviations between said synthetic mixed culture and said control microbiome”. The specification provides example for deduction: “For example, if the microbial composition of the synthetic mixed culture differs upon exposure of a botanical or microbial extract in a way that the microbial species associated with any given skin disease are suppressed in their growth rate, whereas the commensal microbial species show a higher growth, the method can be used as an early diagnostic marker for compounds that are likely to have beneficial effect in the treatment of said skin disease.” (p. 8, lines 20-24). However, it is not clear what is the correlation between compound bioactivity and the relative abundance of pathogenic and commensal microorganisms, whether the bioactivity is considered higher if the amount of commensal microorganisms is higher and/or amount of pathogenic microorganisms is less. Additionally compound may provide not only positive but also negative effect on commensal microorganisms and it is unclear if compound bioactivity is considered to be high or low in the latter case. The scope and boundaries of claim 1 are not certain making claim 1 indefinite.
Dependent claims 2-4, 6-10 and 13-18 do not resolve the issues mentioned above and are rejected.
Claim 3 recites: “bacterial strains are selected from the group consisting of” followed by 5 groups. It is not clear whether strains are selected from any group or groups (A) – (E) respectively and how the recites species within the category relate. The scope and boundaries of claim 3 are not certain since the Markush alternatives are unclear. Claim 3 is interpreted as directed to selection of bacterial strains from any of the recites groups (A) – (E).
Claim 7 recites: “at low agitation rates”. The term “at low agitation rates” is a relative term which renders claim 7 indefinite. The term “at low agitation rates” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The claim recites agitation rates of less than 800 rpm. The specification mentions more preferred agitation rates from 50 rpm to 700 rpm and most preferred from 300 rpm to 600 rpm. However, it is not clear whether any agitation rate of less than 800 rpm is considered low agitation rate. The scope and boundaries of claim 7 are not certain making claim 7 indefinite.
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, 4-10 and 13-15, 17 and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract idea without significantly more. Claim 1 recites a method for screening of the bioactivity of a compound. The method includes step (c) directed to comparing the diversity of the synthetic mixed culture and control microbiome and step (d) of deducing the bioactivity of the compound by deviations between synthetic mixed culture and control microbiome. Comparing is a mental process of looking at the data and comparing the data for the mixed culture with that of control culture and deducing or determining is a mental process of making a conclusion about compound bioactivity based on the comparison.
This judicial exception is not integrated into a practical application because in addition to the comparing and deducing steps, the claim recites steps of providing mixed culture of at least 8 bacterial strains resembling a skin microbiome, cultivating the culture with a compound and measuring the diversity of the mixed culture. The mixed culture is a culture of unspecified microorganisms and resembling a skin microbiome is indefinite limitation as described in 112(b) rejection above. Cultivating the culture with a compound wherein compound is not specified and can be any component of cultivation medium and measuring the diversity of the mixed culture reads like gathering data for comparison and deduction. These steps are recited at high generality and add insignificant extra solution activity to the judicial exceptions.
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because steps of mixing bacterial strains, culturing them with a compound and measuring the relative abundancy of strains is well-understood, routine and conventional as evidenced by Lanzalaco (WO 2013070891 A1 on record in IDS) teaching culturing of skin microorganisms with a test compound and determining replication level compared to a control (p. 4, lines 2-8) and Patzold (WO 2016172196 A1 on record in IDS) teaching compositions comprising mixtures of 2-10 or more different isolated Propionibacterium acnes strains (p. 2, lines 18-19).
Based on the above claim 1 is rejected as ineligible.
Dependent claim 5 is directed to culturing bacterial strains in suspension, claims 7 and 17 to mixing cultures at certain agitation rates, claim 6 to anaerobic culturing and claim 7 to aerobic culturing. Claims 8 and 18 are directed to culturing in laboratory dishes. Claims 13 and 14 are directed to mixtures of at least 10 or 12 bacterial species and claims 4 and 15 are directed to a mixed culture comprising eukaryotic species. These features are recited at high level of generality and are not sufficient to amount to significantly more than the judicial exceptions because they do not alter the judicial exception or make it markedly different. Besides, the conditions for strains culturing and strain selection are recited at a high level of generality and is routine and conventional as evidenced by Lanzalaco, Patzold and Uribe-Alvarez (Uribe-Alvarez et al. FEMS Pathogens and Disease, 2016, 74, ftv111, 1-15). Lanzalaco teaches skin commensal microorganism including both prokaryotes and eukaryotes (p. 7, lines 5-11), culturing of microorganisms in solution of minimal carbo media (p. 12, lines 27-28) and hence in suspension and either anaerobically or aerobically depending on microorganism (p. 24, lines 20-21) and culturing in multi-well vessels, single-well vessels, tubes or conventional test plates (e.g. 12-well plate, 96-well plate) (p. 15, lines 19-22). Patzold teaches compositions including more than 20 strains .” (p. 14, lines 3-5). Uribe-Alvarez teaches aerobic cultivation of S. epidermis under shaking at 250 rpm (p. 2, right column, 2nd paragraph). Therefore, claims 4-8, 13-15, 17 and 18 are rejected as ineligible.
Claim 9 is directed to measuring the diversity by 16S rRNA analysis. Claim is recited at high level of generality and does not amount to significantly more than the judicial exceptions since it do not make contribution over prior art of Patzold teaching 16S rRNA analysis for profiling of microbiomes (p. 32, lines 27-30). Therefore, claim 9 is rejected as ineligible.
Claim 10 is directed to a reference culture without compound. As such claim 10 is not sufficient to amount to significantly more than the judicial exceptions, because it does not alter the judicial exceptions or make them markedly different. Besides, cultivating a reference (control) culture in the absence of test compound is routine and conventional as evidenced by Lanzalaco teaching the control culture cultured in the absence of test agent in the same way as test culture (claim 8). Therefore, claim 10 is rejected as ineligible.
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 1-6, 8-10, 13-15 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Lanzalaco (WO 2013070891 A1 on record in IDS) in view of Patzold (WO 2016172196 A1 on record in IDS).
Regarding claim 1, Lanzalaco teaches methods for identification of test agents that exhibit prebiotic activity on human skin commensal microorganisms (Abstract). Method comprises culturing a test agent with at least one commensal microorganism in minimal media and determining metabolite level or replication level compared to a control (p. 4, lines 2-8). The test agent includes any synthetic or naturally-occurring element or chemical compound (p. 7, line 12). Lanzalaco describes Corynebacterium jeikeium, Staphilococcus epidermis and Propionibacterium acnes as suitable candidate microorganisms for screening agents with prebiotic acidity considering their beneficial function and dominant presence on the skin. Lanzalaco mentions that other skin commensal microorganisms can be used for screening (p. 10, lines 15-21). Lanzalaco discloses that the bioactivity of the test compound is determined by promoting the survival and growth of the microorganism measured by the replication level (p. 14, lines 1, 2, 9, 10). The specification describes comparing the diversity level and/or the diversity profile of mixed culture by the relative abundance: “This includes preferably to determine the relative abundance of the microorganisms comprised in the synthetic mixed culture and the control microbiome and to determine the deviations in relative abundance between the two cultures.” (p. 8, lines 4-6). Thus, comparing the replication level of the test culture compared to control culture corresponds to claimed comparing the diversity level and/or the diversity profile of test culture.
Lanzalaco does not teach the synthetic mixed culture of at least 8 different bacterial strains.
Patzold teaches methods and compositions for changing the composition of the skin microbiome using complex mixtures of bacterial strains (Title). Patzold describes that one or more of bacterial strains are components of the skin microbiome (p. 2, lines 32-33). Patzold discloses that composition can comprise 2-10 or more different Propionibacterium acnes strains (p. 2, lines 18-19) and mentions that some P. acnes strains are pathogenic, while others are not (p. 12, lines 15-16). Patzold describes the non-pathogenic P. acnes strains: “non-pathogenic P. acnes strains consisting of: D1, A5, C3, H1, H2, H3, K1, K2, K4, K6, K8, K9, L1 and F4” (p. 2, lines 23-25). Patzold mentions that composition can further comprise S. epidermidis strains that inhibits or reduces growth of other bacterial strains (p. 2, lines 27-29, p. 17, lines 28-29). Patzold describes that a bacterial composition can be formed from one or more of isolated bacterial strains (p. 17, lines 18-19) that reads on synthetic mixed culture.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Lanzalaco and Patzold and use mixture of isolated bacterial strains from Patzold teaching for method of testing compounds for prebiotic activity taught by Lanzalaco. One would have been motivated to do so since Lanzalaco teach that P. acnes and S. epidermis are dominant commensal bacteria on the skin with beneficial function which can be used for screening, Patzold describes several strains of the same bacteria species in the composition and inclusion of multiple strains in the bacterial composition for screening for compound bioactivity will increase reliability of the screening since different strains can be present on the skin. A skilled artisan would have reasonably expected success in the combination because Lanzalaco and Patzold teach microorganisms of skin microbiome. Thus, Lanzalaco and Patzold teachings render claim 1 obvious.
Regarding claims 4 and 15, Lanzalaco teaches that skin commensal microorganism in his method include both prokaryotes and eukaryotes that can colonize or temporarily inhabit human skin (p. 7, lines 5-11). Lanzalaco describes eukaryotic species from Malassezia, Debaroyomyces and Cryptococcus (p. 7, line 11) that reads on claims 4 and 15. Thus, Lanzalaco and Patzold teachings render claims 4 and 15 obvious.
Regarding claim 5, Lanzalaco teaches culturing of microorganisms in minimal carbon media MCM prepared as solution (p. 12, lines 27-28) and hence bacterial strains are cultivated in suspension. Thus, Lanzalaco and Patzold teachings render claim 5 obvious.
Regarding claims 6, Lanzalaco teaches that microorganisms are cultivated either anaerobically or aerobically depending on microorganism (p. 24, lines 20-21). Thus, Lanzalaco and Patzold teachings render claim 6 obvious.
Regarding claims 8 and 18, Lanzalaco teaches that screening is performed in multi-well vessels, single-well vessels, tubes or conventional test plates (e.g. 12-well plate, 96-well plate) (p. 15, lines 19-22). Thus, Lanzalaco and Patzold teachings render claims 8 and 18 obvious.
Regarding claim 10, Lanzalaco teaches the control culture to be cultured in the absence of test agent in the same way as test culture (claim 8). Lanzalaco describes that water is replacing the test compound in control sample (p. 23, lines 18-19). Thus, Lanzalaco and Patzold teachings render claim 10 obvious.
Regarding claims 2, 3, 9, 13 and 14, Patzold teaches composition of multiple P. acnes strains (p. 2, lines 18-19) that can further comprise S. epidermis strains (p. 17, lines 28-29). Patzold describes that composition can include more than 20 P. acnes strains: “For example, a bacterial composition can comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more than 20 strains of P. acnes.” (p. 14, lines 3-5). P. acnes and S. epidermis species are within the lists of bacterial species for selection of strains in claims 2 and 3. Please see interpretation of claim 3 above in 112(b) section. Patzold mentions that the strains can be genotyped to identify strain (p. 14, lines 7-9) and discloses application of 16S amplification for quantification of diversity in microbial communities (p. 27, lines 16-18). Patzold describes application of 16S rRNA analysis for profiling of donor and recipient microbiomes during transplantation and for monitoring of specific P. acnes strains (p. 32, lines 27-30).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that multiple P. acnes strains and S. epidermis from Patzold teaching can be used for method of screening of compound bioactivity taught by Lanzalaco and that the changes in diversity profile of the bacterial mixtures can be determined by 16S rRNA analysis as described by Patzold. One would have been motivated to assume so because the application of multiple commensal strains will allow to identify compound bioactivity versus different variations of commensal skin bacteria and 16S rRNA analysis was applied by Patzold to quantification of individual P. acnes strains in diverse microbial compositions. A skilled artisan would have reasonably expected success in the combination because Lanzalaco and Patzold teach microorganisms of skin microbiome. Thus, Lanzalaco and Patzold teachings render claims 2, 3, 9, 13 and 14 obvious.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Lanzalaco (WO 2013070891 A1 on record in IDS) in view of Patzold (WO 2016172196 A1 on record in IDS) as described for claims 1 and 4 above, and further in view of Harada (Harada et al. J. Dermatol., 2015, 42, 250-257).
The teachings of Lanzalaco and Patzold have been set forth above.
Although Lanzalaco teaches Malassezia species as skin commensal microorganism in the screening method for compound bioactivity (p. 7, line 11), Lanzalaco does not explicitly teach M. restricta or M. globose species.
Regarding claim 16, Harada teaches multiple Malassezia species which are commensal and pathogenic fungi and mentions that Malassezia are dominant fungi on human body (Abstract). Harada discloses that M. restricta and M. globose are the predominant Malassezia species of healthy skin (p. 251, Table 1, right column, 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Harada teaching and add M. restricta and/or M. globose species as eukaryotic microorganism to the method for screening compound bioactivity based on Lanzalaco and Patzold teachings. One would have been motivated to do so because the Lanzalaco teach inclusion of Malassezia as commensal microorganism in screening method and Harada teaches M. restricta and M. globose to be the predominant Malassezia species of healthy skin. A skilled artisan would have reasonably expected success in the combination because Lanzalaco, Patzold and Harada teach microorganisms of skin microbiome. Thus, Lanzalaco, Patzold and Harada teachings render claim 16 obvious.
Claims 7 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Lanzalaco (WO 2013070891 A1 on record in IDS) in view of Patzold (WO 2016172196 A1 on record in IDS) as described for claim 1 above, and further in view of Uribe-Alvarez (Uribe-Alvarez et al. FEMS Pathogens and Disease, 2016, 74, ftv111, 1-15).
The teachings of Lanzalaco and Patzold have been set forth above.
Although Lanzalaco teaches aerobic cultivation for S. epidermis (p. 23, lines 5-6), Lanzalaco does not specify the agitation rates.
Uribe-Alvarez teaches aerobic cultivation of S. epidermis under shaking at 250 rpm (p. 2, right column, 2nd paragraph). That reads on limitation of claim 7 and very close to lower level of limitation for agitation rate of 300 rpm in claim 17. Uribe-Alvarez mentions that S. epidermis can survive in a wide range of O2, however, low oxygen promotes cell-adhesion and biofilm formation (p. 2, left column, 3rd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use aerobic cultivation with low agitation rates for S. epidermis as described by Uribe-Alvarez for method of screening of compound bioactivity based on Lanzalaco and Patzold teachings. One would have been motivated to do so since Uribe-Alvarez teaches that low oxygen promotes cell-adhesion and biofilm formation of S. epidermis and hence aerobic cultivation will promote S. epidermis growth in liquid medium. A skilled artisan would have reasonably expected success in the combination because Lanzalaco and Uribe-Alvarez teach aerobic cultivation for S. epidermis and Lanzalaco, Patzold and Uribe-Alvarez teach microorganisms of skin microbiome. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the agitation rate during bacterial cultivation is the result effective variables. One would have been motivated to optimize the agitation rate depending on the format of culturing (e.g. vessel, multi-well plate) to achieve faster bacterial growth. A skilled artisan would have reasonably expected success in this optimization because adjustment of agitation rate during cultivation is routine and conventional.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila G Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653