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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Status of the Application
Applicant’s arguments and amendment submitted on 8/11/2025 are acknowledged.
Claims 42, 47-49, 52-53, and 62-73 are pending.
Claim 42 is amended.
Claims 1-41, 43-46, 50-51, and 54-61 are canceled.
Claims 62-73 are new.
Claims 42, 47-49, 52-53, and 62-73 have been examined on the merits.
Priority
This application, U.S. Application number 17/421917, is a national stage entry of International Application Number PCT/EP2020/050267, filed on 01/08/2020, which claims foreign priority under 35 U.S.C. 119(a)-(d) to EP 19151165.8 filed on 01/10/2019.
However, Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(a)-(d) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AlA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Foreign Application EP 19151165.8, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, EP 19151165.8 does not disclose the cell amounts “below 1 wt%”, “below 0.1 wt%”, “below 0.005 wt%”, and “0.001 wt%” recited in the claims 42, 52-53, and 73, respectively. Accordingly, instant claims 42, 47-49, 52-53, and 62-73 do not receive the benefit of the filing date of the Foreign Application EP 19151165.8. The effective filing date of instant claims is the filing date of the internation application, 01/08/2020.
Objections - Withdrawn
Objection to the claims 54 and 59 is withdrawn due to the cancellation of the claims filed on 8/11/2025.
Rejections - Withdrawn
The rejection of Claims 54-59 under 35 U.S.C. 101 is withdrawn due to the cancellation of the claims filed on 8/11/2025.
The rejection of Claims 42-59 under 35 U.S.C. 112(a) as failing to comply with the enablement requirement is withdrawn due to Applicant’s submission of the statement about availability of the biological material (B. subtilis DSM 32315, B. subtilis DSM 32540, B. subtilis DSM 32592, B. licheniformis DSM 32314, B. pumilus DSM 32539) to the public in the response filed on 8/11/2025 (page 7) as well as in the specification amended on 8/11/2025.
The rejection of Claims 42-59 under 35 U.S.C. 112(b) is withdrawn due to the amendment to or cancellation of the claims filed on 8/11/2025.
The rejection of 42-45 and 47-59 under 35 U.S.C. 103 over Petri et al. is withdrawn due to the amendment to or cancellation of the claims filed on 8/11/2025.
18. The provisional rejection of Claims 54-59 on the ground of nonstatutory obviousness-type double patenting over claims of copending Application No. 16627195 is withdrawn due to the cancellation of the instant claims filed on 8/11/2025.
The rejection of Claims 42 and 50-59 on the ground of nonstatutory obviousness-type double patenting over claims of Patent No. 11173184 is withdrawn due to the amendment to or cancellation of the instant claims filed on 8/11/2025.
The rejection of Claims 42-45 and 47-59 on the ground of nonstatutory obviousness-type double patenting over claims of Patent No. 11173184 in view of Guilhabert-Goya is withdrawn due to due to the amendment to or cancellation of the instant claims filed on 8/11/2025.
The rejection of Claims 42-59 on the ground of nonstatutory obviousness-type double patenting over claims of Patent No. 11173184 in view of Guilhabert-Goya and Zhang is withdrawn due to due to the amendment to the instant claims as well as Examiner’s further consideration.
Claim Objections
Claim 73 is objected to because of the recitation of “below 0.001 wt.-%”. To be consistent with the terms previously recited in the claims 42 and 52-53, the recited term should be changed “less than 0.001 wt%”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(d), or 112, Fourth Paragraph
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 62 and 63 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends
The base claim 42 is directed to a method for producing a dried fermentation broth, which recites the limitation “after separating the microorganisms in step b), the fermentation broth is concentrated”; whereas the dependent claim 62 recites the limitation “the fermentation broth is concentrated after separating the microorganisms”, and the dependent claim 63 recites the limitation “the fermentation broth is concentrated before separating the microorganisms”. Therefore, Claim 62 fails to further limit the method of Claim 42, and the scope of Claim 63 is broader than that of Claim 42.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
Claims 42, 47-49, 52-53, 62-64, 66, and 70-73 are rejected under 35 U.S.C. 103 as being unpatentable over Petri et al. (US 2017/0340683, 2017, cited in IDS) in view of Zhang et al. (International Journal of Food Properties, 2014, 17:1237–1253, of record).
US 2017/0340683 is equivalent to US Patent No.11173184 (published in 2021, effective filing date: May 31, 2016). Accordingly, the instant claims are also rejected under 35 U.S.C. 103 over Petri et al. (US Patent No.11173184) over Zhang et al. All citations are made to US 2017/0340683.
Petri et al. teach a Bacillus subtilis strain DSM 32315 as well as a preparation derived from the B. subtilis strain (abstract, paras 0004-0007 and 0010), wherein the preparation is a cell-free fermentation broth derived from a culture of the B. subtilis strain, which is produced by centrifuging and/or filtrating a fermentation broth obtained from culturing the bacterial strain, followed by removing microbial cells from the fermentation broth to obtain the cell-free fermentation (i.e. supernatant) (para 0106, lines 1-6; para 0108, lines 1-2, 3-5, and last 2 lines), wherein the cell-free fermentation broth preferably is a supernatant of the fermentation broth (i.e. a cell-free liquid portion of the fermentation broth), which contains a mixture of compounds, such as metabolites, enzymes and peptides, secreted by cells into surrounding fermentation medium (para 0108, last 7 lines); and the fermentation broth is dried with or without addition of carriers by using conventional drying processes such as spray drying (para 0107, lines 1-3); wherein B. subtilis DSM 32315 and fermentation broth/metabolites inhibit growth of pathogenic C. perfringens of poultry as well as pathogenic S. suis (paras 0004, 0063/lines 1-7 and13, 0078; Examples 5 and 10); and wherein the fermentation broth is used as probiotic ingredient (DFM) in animal feed or food products for improving health of animals such as poultry (paras 0046, 0051 and 0078), and the fermentation broth comprises enzymes, e.g. cellulase and xylanase and it is used as a feed additive (paras 0097-0099, para 0108/lines 4 from bottom, para 0136). Overall, Petri et al. teach a dried cell-free fermentation broth (supernatant) of B. subtilis strain DSM 32315 as well as a method of preparing such a fermentation broth, comprising steps: (a) culturing the B. subtilis strain DSM 32315 in a fermentation medium to obtain a fermentation broth; (b) centrifuging and/or filtering the fermentation broth and separating cells from the fermentation broth to obtain a cell-free fermentation broth (supernatant) (cell-free liquid portion of the fermentation broth); and (c) drying the resulting fermentation broth/supernatant with or without addition of carriers by a conventional process such as spraying drying.
Regarding the limitation “separating at least 99% of the microorganisms …” in the step (b) of claim 42 as well as the further limitations of the cell amounts “below 1 wt%”, “below 0.1 wt%”, “below 0.005 wt%”, and “below 0.001 wt%” recited in claims 42, 52-53 and 73, Petri et al. do not expressively teach a specific amount of cells to be removed from the fermentation broth or a specific cell amount still present in the dried fermentation broth/supernatant. However, Petri et al. teach the preparation is a cell-free fermentation broth (supernatant) comprising a mixture of compounds secreted by cells into surrounding fermentation medium, whose scope encompasses those cell-free fermentation broth having the claimed cell amounts. Given cells are not a requirement component in the cell-free preparation of Petri et al., one of ordinary skill in the art would have realized that cells can be completely removed from the fermentation broth for preparing the cell-free fermentation broth/supernatant. As such, it would have been obvious to one of ordinary skill in the art to remove at least 99% cells from the fermentation broth of B. subtilis strain DSM 32315 through centrifugation and/or filtration in the method of Petri et al. for preparing the dried cell-free fermentation broth/supernatant, thus arriving at the claimed dried fermentation broth containing cells at an amount below 1 wt%, 0.1 wt%, 0.005 wt% or 0.005 wt%. Furthermore, it should be noted that "[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” (see MPEP 2144.5, (Il)-A). Examiner takes the position that the claimed method of removing microbial cells at the claimed ranges as well as the claimed fermentation broth having cells in the claimed ranges would be obvious over the teachings of Petri et al., in the absence of evidence of criticality.
Regarding the limitations that the fermentation broth inhibits pathogenic bacteria C. perfringens and/or S. suis and reduces/eliminates antinutritional factors (ANFs) in the claim 42, Petri et al. teach that the fermentation broth inhibits growth of C. perfringens and S. suis, and Petri et al. are silent about its effect on reducing or eliminating ANFs. However, the claimed limitations are directed to properties, rather than structures, of the fermentation broth produced by the claimed method. Petri et al. suggest a fermentation broth having all the structural limitations of the dried fermentation broth recited in Claim 42. In the absence of evidence to the contrary, it is presumed that a dried fermentation broth having substantially the same structures possesses the same properties. Therefore, the teachings of Petri et al. meet the requirement of the claimed limitations.
Regarding limitations about the solvent evaporation recited in the claim 42, Petri et al. teach a process of solvent evaporation to obtain the dried fermentation broth (para 0107, line 5). It is noted that this drying process inherently comprises concentrating the fermentation broth through solvent evaporation, because liquid solvent in liquid fermentation broth must be evaporated before the liquid fermentation broth becomes dried, and such solvent evaporation gradually increases the total dry matter of the fermentation broth until it is completely dried. Furthermore, Petri et al. expressively teach a step of concentrating the fermentation broth by solvent evaporation to obtain a concentrate of fermentation broth, before the concentrate is further dried (para 0106/page 7/lines 1-3, plage 5/left col/last 2 lines, para 0107/lines 1-3). As such, carrying out the solvent evaporation for concentrating the fermentation broth and increasing its total dry matter would be well within the purview of one of ordinary skill in the art having the cited reference as a guide.
Petri et al. do not expressively teach applying a rotary evaporator for concentrating the fermentation broth through solvent evaporation. However, Petri et al. teach applying a conventional evaporation process for concentrating the fermentation broth (page 7, left col, lines 1-3).
Zhang et al. teach a highly similar method for producing a dried cell-free fermentation broth of Bacillus subtilis, comprising: preparing a peanut meal (fermentation medium); culturing a strain of B. subtilis by inoculating the B. subtilis in the peanut meal to obtain a fermented peanut meal (i.e. fermentation broth); centrifuging the broth to obtain a supernatant (i.e. cell-free liquid portion of fermentation broth) and filtering the supernatant to obtain a filtrate, i.e. cell-free fermentation broth; concentrating the cell-free fermentation broth by using a rotary evaporator through solvent evaporation, followed by freeze-drying (page 1239, para 4), thus generating a dried cell-free fermentation broth. It is noted that the steps in the method of Zhang et al. are comparable to all the steps in instant claims 42 and 44-46 and also comparable to all the steps in the method of Petri et al.
It would have been obvious to apply a rotary evaporator in the method of Petri et al. for concentrating through solvent evaporation the cell-free fermentation broth of B. subtilis DSM 32315, thus obtaining a concentrated cell-free fermentation broth before the drying step is further conducted, as taught by Zhang et al. One of ordinary skill in the art would have been motivated to do so, because Petri et al. teach applying a conventional evaporation process for concentrating the fermentation broth, and the solvent evaporation using a rotary evaporator is a conventional solvent-evaporation process commonly used in the art for concentrating fermentation products/fermentation broth, as supported by Zhang et al. Furthermore, Zhang et al. demonstrate that the rotary evaporator is effective at removing solvent through evaporation from B. subtilis fermentation broth before the resulting concentrate is further dried. One of ordinary skill in the art has a reasonable expectation of success at applying the rotary evaporator of Zhang et al. for solvent evaporation in the method of Petri et al. because both the method of Zhang et al. and method of Petri et al. are directed to preparation of a dried fermentation broth of B. subtilis through concentrating and then drying cell-free fermentation broth, and the teachings of Zhang et al. are readily applicable to the method of Petri et al.
Regarding Claims 47-49, Petri et al. teach adding carriers/substances to the fermentation broth before starting the drying processes, as indicated above. Petri et al. further teach that suitable carriers are selected from anti-caking agents, anti-oxidation agents, bulking agents, and/or protectants for improving recovery, efficacy, and physical properties of resulting preparations (para 0085, lines 4-6). It is noted that the limitation “to preserve enzymes” in Claim 47 is directed to the intended use and it does not further limit the structure of the recited substances. Therefore, the teachings of Petri et al. renders the claims 47-48 obvious. Regarding the additional limitation in Claim 49, Petri et al. teach adding the preparation of their invention (including dried fermentation broth) to a feed/carrier substance at an amount from 0.1 wt% to 10 wt% (para 0073, lines 2-4), to be administered to an animal in need of treatment and protection (para 0068). Petri et al. are silent about a specific amount of carriers added to the pre-dried fermentation broth. However, it is considered that the amount of Petri et al. can be readily modified by routine optimization for adding carriers to a fermentation broth before drying processes, for reaching desirable effects on improving recovery, efficacy, and physical properties of the resulted dried formation broth, and at the same time for ascertaining that the dried formation broth delivers effective treatment and protection to animal after being administered along with a feed. Furthermore, it is well settled that routine optimization is not patentable, even though it results in significant improvement over the prior art (see MPEP 2144.05). Examiner takes the position that the claimed concentration range “between one fifth to equal” recited in claim 49 would be obvious over the teachings of Petri et al. in the absence of any showing of unexpected results or criticality.
Regarding Claim 63, Petri et al. do not teach concentrating the fermentation broth before separating cells of B. subtilis DSM 32315. However, Petri et al. teach concentrating fermentation broth and drying fermentation broth concentrates (para 0107/lines 1-3). It is a matter of an obvious design choice and routine optimization to concentrate the fermentation broth and then separate microbial cells before drying obtained fermentation broth concentrate, which is well within the purview of one of ordinary skill in the art. Examiner notes that an order of performing steps (in the instant case, the order of performing the concentrating step and separating step) is prima facie obvious, absence evidence of criticality. See MPEP 2144.04(IV)(C).
Regarding Claims 70-72, Petri et al. teach the metabolites of B. subtilis DSM 32315 inhibit growth of pathogenic C. perfringens as well as pathogenic S. suis.
Petri et al. are silent about inhibitory effects before and after drying. However, the claimed limitations about inhibitory effect of the fermentation broth are directed to properties, rather than structures, of the fermentation broth produced by the claimed method. The fermentation broths of Petri et al. have all the structural limitations of the un-dried and dried fermentation broth recited in the claims. In the absence of evidence to the contrary, it is presumed that a dried or non-dried fermentation broth having substantially the same structures possesses substantially the same properties. Therefore, the teachings of Petri et al. render the claims obvious.
Regarding the claim 66, Petri et al. further teach that the fermentation broth preferably comprises that from B. licheniformis DSM 32314 (para 0094, lines 8-12). Thus, it would have been obvious to culture B. licheniformis DSM 32314 in the method of Petri et al. for preparing a dried cell-free fermentation froth of B. licheniformis DSM 32314
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 69 is rejected under 35 U.S.C. 103 as being unpatentable over Petri et al. (US 2017/0340683, 2017, cited in IDS) in view of Zhang et al. (International Journal of Food Properties, 2014, 17:1237–1253, of record), as applied to Claims 42,47-49, 52-53, 62-64, 66, and 70-73, further in view of Diaz (Engormix, 2007, pages 1-8, retrieved from the URL of http://en.engormix.com/MA-poultry-industry/articles/ effect-bacillus-amyloliquefaciens-cect5940-t795/p0.htm).
US 2017/0340683 is equivalent to US Patent No.11173184 (published in 2021, effective filing date: May 31, 2016). Accordingly, the instant claims are also rejected under 35 U.S.C. 103 over Petri et al. (US Patent No.11173184) over Zhang et al. and Diaz. All citations are made to US 2017/0340683.
The teachings of Petri et al. and Zhang et al. are described above.
Regarding the claim 69, Petri et al. do not teach cultivating Bacillus amyloliquefaciens CECT-5940 for preparing the dried cell-free fermentation broth. However, Petri et al. teach including additional probiotics in the preparation/fermentation broth of their invention (para 0089/line 6).
Diaz teaches that probiotics are used in poultry feed for promoting growth of and providing therapeutic effect to poultry (page 1/para 1). Diaz further teaches B. amyloliquefaciens CECT-5940 is a Bacillus probiotic, which releases huge quantity of extracellular enzymes to surrounding culture media (fermentation broth) thus allowing animals/poultry to obtain high degradability of nutrients in feed/poultry feed, and facilitates lactic acid production that causes a severe drop in intestinal pH and inhibits pathogenic bacteria, and is able to produce inhibitory substances (bacteriocins) that inhibit growth of pathogenic bacteria, e.g. C. perfringens (pages 1-2, and page 6/Conclusion/para 1). Diaz further teaches preparing a supernatant (i.e. cell-free fermentation broth) from a culture of B. amyloliquefaciens CECT-5940, which comprises: cultivating B. amyloliquefaciens CECT-5940 in a fermentation medium such as Nutrient Broth and TSB medium, and obtaining cell-free fermentation broth by separating cells from cell culture through centrifugation (page 2, para 4). Diaz demonstrates that the cell-free fermentation broth of B. amyloliquefaciens CECT-5940 effectively inhibits growth of pathogenic bacteria: Clostridium perfringens, Escherichia coli, and Yersinia enterocolitica (see results in tables of pages 2 and 3).
It would have been obvious to further cultivate B. amyloliquefaciens CECT-5940 in the method suggested by Petri et al. and Zhang et al. for obtaining a dried cell-free fermentation broth to be combined with the dried cell-free fermentation broth of B. subtilis DSM 32315 as a probiotic ingredient in animal feed for improving health of and controlling pathogenic bacteria in animals/poultry. One of ordinary skill in the art would have been motivated to do so, because Petri et al. teach further including additional probiotics in their fermentation broth preparation (as a feed additive). Furthermore, it is well known in the art that B. amyloliquefaciens CECT-5940 is a probiotic bacterium and the cell-free fermentation broth of this probiotic provides the benefits of enhancing degradability of nutrients in animal feed, facilitating lactic acid production in the intestine for maintaining a healthy microbial population, and effectively inhibiting growth of pathogenic bacteria including C. perfringens, E. coli, and Y. enterocolitica, as supported by Diaz. One of ordinary skill in the art has a reasonable expectation of success at modifying the method suggested by Petri et al. and Zhang et al. for improving growth-promoting and therapeutic effect of the cell-free fermentation broth when being used as a feed additive, because the addition of cell-free fermentation broth of B. amyloliquefaciens CECT-5940 is expected to further improve availability of digested nutrients to animals, inhibiting pathogenic bacteria, and maintaining a healthy microbial population in the intestine.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 65 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Petri et al. (US 2017/0340683, 2017, cited in IDS) in view of Zhang et al. (International Journal of Food Properties, 2014, 17:1237–1253, of record), as applied to Claims 42,47-49, 52-53, 62-64, 66, and 70-73, further in view of Pelzer et al. (WO 2019/002471, published on Jan. 3, 2019, its equivalent application US 2020/0113952 is cited in IDS).
It is noted that US 2020/0113952 (published in Apr. 2020, cited in IDS) is equivalent to WO 2019/002471 and all citations are made to US 2020/0113952.
The teachings of Petri et al. and Zhang et al. are described above.
Regarding the claim 65, Petri et al. do not teach cultivating Bacillus subtilis strain DSM 32540 for preparing the dried fermentation broth. However, Petri et al. teach including additional Bacillus subtilis probiotics in the preparation/fermentation broth of their invention (para 0094, line 4).
It would have been obvious to further cultivate B. subtilis DSM 32540 in the method suggested by Petri et al. and Zhang et al. for obtaining a dried cell-free fermentation broth to be combined with the dried cell-free fermentation broth of B. subtilis DSM 32315 as a probiotic ingredient in animal feed for improving health of and controlling pathogenic bacteria in animals/poultry. One of ordinary skill in the art would have been motivated to do so, because Petri et al. teach further including additional B. subtilis probiotics in their fermentation broth preparation (as a feed additive). Furthermore, it is known in the art that B. subtilis DSM 32540 is a probiotic bacterium and the cell-free fermentation broth of this probiotic provides the benefits of inhibiting growth of main commercially relevant pathogens of poultry, including C. perfringens, S. suis, C. difficile, S. gallinaceus, C. coli and E. cecorum. Moreover, it is known in the art to combine B. subtilis DSM 32540 with B. subtilis DSM 32315 of Petri et al. in the animal feeds for providing beneficial effects to animals/poultry. In support, Pelzer et al. teach B. subtilis DSM 32540 exhibits advantageous features of inhibiting growth of C. perfringens, S. suis, C. difficile, S. gallinaceus, C. coli and E. cecorum, the main commercially relevant pathogens of swine and poultry (paras 0004-0005); wherein B. subtilis DSM 32540 is prepared as a cell-free fermentation broth, as the cells secret metabolites, enzymes and peptides into the surrounding medium, and the supernatant of the cells comprises a mixture of these compounds; a preferred preparation is a cell-free supernatant of the fermentation broth (para 0126); and wherein the preparation/fermentation broth is used as a probiotic ingredient in feed or food products (para 0054). Pelzer et al. further teach that B. subtilis DSM 32315 can be included as additional probiotic along with DSM 32540 in the fermentation broth preparation for feeding animals/poultry (para 0112, lines 14).
Regarding Claim 67, Pelzer et al. further teach including Bacillus DSM 32539 along with B. subtilis DSM 32315 as additional probiotics in the fermentation broth preparation for feeding animals/poultry (para 0112, lines 9 and 14). Thus, it would have been obvious to culture Bacillus DSM 32539 in the method suggested by Petri et al. and Zhang et al. for preparing a dried cell-free fermentation froth of DSM 32539
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 65 and 67-69 are rejected under 35 U.S.C. 103 as being unpatentable over Petri et al. (US 2017/0340683, 2017, cited in IDS) in view of Zhang et al. (International Journal of Food Properties, 2014, 17:1237–1253, of record), as applied to Claims 42,47-49, 52-53, 62-64, 66, and 70-73, further in view of Ochrombel et al. (WO 2019/206820, published on Oct. 31, 2019, cited in IDS).
The teachings of Petri et al. and Zhang et al. are described above.
Regarding the claims 65 and 67-69, Petri et al. do not teach cultivating B. subtilis DSM 32540, B. pumilus DSM 32539, B. subtilis DSM 32592, or B. amyloliquefaciens CECT-5940 for preparing the dried fermentation broth.
It would have been obvious to try to further cultivate B. subtilis DSM 32540, B. pumilus DSM 32539, B. subtilis DSM 32592, or B. amyloliquefaciens CECT-5940
in the method suggested by Petri et al. and Zhang et al. for obtaining a dried cell-free fermentation broth to be combined with the dried cell-free fermentation broth of B. subtilis DSM 32315 as a probiotic ingredient in animal feed for improving health of and controlling pathogenic bacteria in animals/poultry. One of ordinary skill in the art would have been motivated to do so, because Petri et al. teach further including additional probiotics in their fermentation broth preparation (as a feed additive). Furthermore, it is known in the art that B. subtilis DSM 32540, B. pumilus DSM 32539, B. subtilis DSM 32592, and B. amyloliquefaciens CECT-5940 are probiotic bacteria, just like B. subtilis DSM 32315 and DSM 32314 taught by Petri et al., and these probiotics inhibit pathogenic bacteria and stimulate a systemic immune response in animals and human beings, when being used as feed or food additive, as supported by Ochrombel et al. (page 4/lines 15-25, page 8/lines 16-17, page 3/line 21). It is further noted that Ochrombel et al. teach preferably using the 6 probiotics: B. subtilis DSM 32540, B. pumilus DSM 32539, B. subtilis DSM 32592, B. amyloliquefaciens CECT-5940, B. subtilis DSM 32315 and B. licheniformis DSM 32314, and they do not specifically teach using these probiotics in the form of cell-free fermentation broth. However, Petri et al. teach using B. subtilis DSM 32315 and B. licheniformis DSM 32314, two of these 6 probiotics, in the form of cell-free fermentation broth as probiotic additive of animal feeds. It would have been obvious to try culturing the rest 4 probiotics (B. subtilis DSM 32540, B. pumilus DSM 32539, B. subtilis DSM 32592, or B. amyloliquefaciens CECT-5940) respectively in the method suggested by Petri et al. and Zhang et al. for obtaining their dried cell-free fermentation broth to be used as a probiotic ingredient in animal feed. See MPEP 2143 I.E., the rationale “obvious to try” supports a conclusion of obviousness when there is a finite number of identified and predictable solutions in the prior art, and choosing from such a finite number of identified and predictable solutions would have a reasonable expectation of success.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments about the claim objection as well as the claim rejections under 35 USC 112(b), 101, and 112(a) in the response filed on 8/11/2025 (pages 6-7) have been fully considered but they are moot because the objection and rejections have been withdrawn, as indicated above.
Applicant's arguments about the provisional rejection of claims 54-59 on the ground of obviousness-type double patenting over claims of copending Application No. 16627195 in the 8/11/2025 response (pages 10-11) have been fully considered but they are moot because the rejection has been withdrawn, as indicated above.
Applicant's arguments about the rejections of claims 42-45, 46, and/or 47-59 on the ground of obviousness-type double patenting over claims of Patent No. 11173184 either alone or in combination with Guilhabert-Goya and/or Zhang in the 8/11/2025 response (pages 10-12) have been fully considered but they are moot because the rejections have been withdrawn, as indicated above.
Applicant's arguments about the rejection of claims 42-45 and 47-59 under 35 USC 103 over Petri et al. in the 8/11/2025 response (page 7, last para) have been fully considered but they are moot because the rejection has been withdrawn, as indicated above.
Applicant's arguments about the rejection of claims 42-59 under 35 USC 103 over Petri et al. in view of Zhang in the 8/11/2025 response (pages 8-10) have been fully considered but they are not persuasive for the following reasons.
Applicant’s arguments based on motivation to combine Zhang with Petri in the 8/11/2025 response (pages 8-9) are misleading and unpersuasive. Zhang expressively teaches a method of producing a dried cell-free fermentation broth of B. subtilis, comprising steps: cultivating a B. subtilis strain in a culture medium, separating cells from fermentation broth by centrifugation and filtering to obtain a cell-free fermentation broth, concentrating the cell-free fermentation broth by a rotary evaporator through solvent evaporation, and further drying the concentrated broth. The method of Zhang is highly similar to the method of Petri, and all the steps of Zhang are comparable to all the steps of Petri. One of ordinary skill in the art would have been motivated to combine the teachings of Zhang and Petri by applying a rotary evaporator of Zhang for concentrating the B. subtilis fermentation broth of Petri through solvent evaporation, because Petri teaches concentrating their fermentation broth through solvent evaporation by using a conventional technique, and Zhang demonstrates that rotary evaporator is a conventional technique in the art for effectively concentrating fermentation broth of B. subtilis. Furthermore, Examiner notes that being used as an antioxidant peptide preparation is directed to the intended use of the dried cell-free fermentation broth prepared by Zhang. Given Petri et al. expressively teach their dried cell-free fermentation broth is applied as a probiotic ingredient in animal feeds, one of ordinary skill in the art would have recognized that the dried cell-free fermentation broth prepared by using a rotary evaporator for solvent evaporation in the modified method of Petri et al. can be readily used as probiotic ingredient in animal feeds. With regard to Applicant’s arguments based on scale of sample preparation in page 9/para 3 of the response, they are not persuasive. It is noted that the drying step of Petri is carried out at various different scales by drying techniques such as freeze drying, tray drying, and spray drying; and the concentrating step is a step conducted before the drying step in the method of Petri, so this step only requires to remove a part of the solvent from the fermentation broth. In addition, Petri et al. only requires adding the dried fermentation broth to animal feeds at an amount as low as 0.1 wt% for feed application (see para 0073). As such, the process of concentrating fermentation broth in the method of Petri is not necessarily at a large scale, and the rotary evaporation of Zhang can be well-suited for solvent evaporation in the method of Petri, even assuming lab-scale rotary evaporation is used in his method (Note: Zhang is silent about the maximum capability of the rotary evaporator). Furthermore, the rotary evaporation of Zhang can be readily scaled up for a larger scale of concentration process if it is needed in the method of Petri. As such, the concentration technique of Zhang is readily applicable to the method of Petri for preparing the concentrated fermentation broth without affecting properties or function of the fermentation broth.
Applicant’s arguments in the section of not establishing a reasonable expectation of success in the 8/11/2025 response (pages 9-10) are not persuasive. It is noted that Applicant’s arguments about no mechanism for regenerating enzymes in the cell-free fermentation broth and rehydrating the broth to yield a preparation retaining enzyme activity are not relevant to combining the teachings of Zhang and Petri in the 103 rejection; and the arguments are based on the features not recited in the claims. Furthermore, the techniques for preserving enzymatic and antibacterial activities are well established in the art. There is no novelty in the instant claims about reciting a step of drying a cell-fermentation broth.
Applicant’s arguments in paras 3-4 of page 10 in the 8/11/2025 response are not persuasive. It is noted that the scope of the cell-free fermentation broths of Petri encompasses those broths having the claimed microbial amounts, which render the claimed invention to be obvious, in the absence evidence of criticality of the claimed amounts, as indicated above. With regard to Applicant’s arguments based on ANF activity, it is noted that ANF activity is an inherent feature of the dried cell-free fermentation broth of B. subtilis DSM 32315. The dried cell-free broth of DSM 32315 prepared by the method suggested by Petri et al. has all the structures recited in the claims, thus being presumed to have the same property about ANF activity, as indicated above. Applicant failed to provide any factual evidence in the response to support the dried cell-free fermentation broth prepared by the method of Petri does not have the claimed ANF activity.
Overall, the conclusion of the obviousness of the claims 42, 47-49, 52-53, and 62-73 has been established for all the reasons indicated above.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Qing Xu, Ph.D., whose telephone number is (571) 272-3076. The examiner can normally be reached on Monday-Friday from 9:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached at (571) 272-0939. Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to the receptionist whose telephone number is (571) 272-1600.
/Qing Xu/
Patent Examiner
Art Unit 1656