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 .
Remarks
The amendments and remarks filed on 03/29/2026 have been entered and considered. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior office action. The rejections and/or objections presented herein are the only rejections and/or objections currently outstanding. Any previously presented objections or rejections that are not presented in this Office Action are withdrawn. Claims 74-88 are pending; Claims 1-73 are cancelled; Claims 74-88 are new; and Claims 74-88 are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/01/2026
is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97 and has been considered by the examiner.
Withdrawal of Objections
The objection to Claim 73 is withdrawn due to the cancellation of the claim.
Withdrawal of Rejections
The rejection of Claims 62 and 63 under 35 U.S.C. 112(d) is withdrawn due to the cancellation of the claims.
The rejections of Claims 42, 47-49, 52-53, and/or 62-73 under 35 U.S.C. 103 Petri et al. in view of Zhang, Diaz, Pelzer et al., and/or Ochrombel et al. are withdrawn due to the cancellation of the claims.
Claim Rejections - 35 USC § 103
Claims 74, 77-81, 83, and 87 are rejected under 35 U.S.C. 103 as being unpatentable over Petri-2 et al. (US 2021/0228653, 2021, effective filing date: May 24, 2017, cited in IDS).
US 2021/0228653 is equivalent to WO 2017/207371 (published on Dec. 7, 2017). Accordingly, the instant claims are also rejected under 35 U.S.C. 103 over Petri-2 et al. (WO 2017/207371). All citations are made to US 2021/0228653.
Petri-2 et al. teach a probiotic Bacillus licheniform strain DSM 32314 as well as a preparation derived from the B. licheniform strain to be used as a probiotic agent for inhibiting pathogens (abstract, paras 0004-0007 and 0010) (Note: the strain DSM 32314 reads on the microorganisms specifically defined in the step a) of claims 74 and 83), wherein the preparation is a cell-free fermentation broth derived from a culture of the B. licheniform strain, which is produced by centrifuging and/or filtrating a fermentation broth obtained from culturing DSM 32314 in a fermentation medium, followed by removing microbial cells from the fermentation broth to obtain the cell-free fermentation broth (i.e. supernatant) (para 0106: lines 1-6; para 0108: lines 1-2, 4-6, and last 3 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 then dried with or without addition of carriers by using conventional drying processes such as spray drying, freeze drying, or evaporation (para 0107, lines 1-5); wherein B. licheniform DSM 32314 and fermentation broth/metabolites of DSM 32314 inhibit growth of pathogenic bacteria including C. perfringens and S. suis in animals such as poultry (paras 0004, 0065/lines 1-7 and 13, 0076, 0080-81; Examples/paras 0138, and 0154); and wherein the fermentation broth preparation is used as probiotic ingredient (DFM) in animal feed or food products for improving health of animals such as poultry (paras 0048, 0053-54, and 0080-81), and the fermentation broth preparation comprises extracellular enzymes, e.g. proteases, cellulase, and xylanase, as active components (para 0108/line 4 from bottom, and para 0111). Petri-2 et al. further teach that the additional probiotics, preferably B. subtilis DSM 32315, are used for preparing fermentation broth (para 0095, lines 8-12) (Note: this teaching renders the limitation about combination of B. licheniform DSM 32314 with B. subtilis DSM 32315 in the claim 74 to be obvious).
Overall, Petri-2 et al. teach a dried cell-free fermentation broth (a dried supernatant) of B. licheniform strain DSM 32314 as well as a method of preparing such a fermentation broth, comprising steps: (a) culturing B. licheniform strain DSM 32314 in a fermentation medium to obtain a fermentation broth containing DSM 32314; (b) separating microbial cells from the fermentation broth, by centrifuging and/or filtering the fermentation broth and removing 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, freeze drying, or solvent evaporation, and wherein an additional probiotic B. subtilis DSM 32315 may be combined with B. licheniform DSM 32314 for preparing the fermentation broth.
Regarding the limitation “separating at least 99% of the microorganisms … the amount of cells … is below 1 wt%” in the steps (b) and (c) of claim 74 as well as the further limited cell amounts “below 0.1 wt%” and “below 0.005 wt%” in claims 80 and 81, Petri-2 et al. do not expressively teach a specific amount of cells to be removed from the fermentation broth or a specific amount of cells remained in the dried fermentation broth/supernatant. However, Petri-2 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-2 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 of Petri-2 et al. 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. licheniform DSM 32314 through centrifugation and/or filtration in the method of Petri-2 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%, 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 dried fermentation broth having cells in the claimed ranges would be obvious over the teachings of Petri-2 et al., in the absence of evidence of criticality.
Regarding the limitations about inhibiting C. perfringens and/or S. suis and reducing ANFs in feed recited at the end of the claim 74, Petri-2 et al. teach that their fermentation broth inhibits growth of pathogenic bacteria C. perfringens and S. suis. Petri-2 et al. are silent about its effect on reducing or eliminating ANFs in a feed. However, the claimed limitations are directed to properties, rather than structures, of the fermentation broth produced by the claimed method. Petri-2 et al. suggest a fermentation broth having all the structural limitations of the dried fermentation broth recited in Claim 74. 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-2 et al. meet the requirement of the claimed limitations.
Regarding the limitations about concentrating the fermentation broth in the claims 74 and 87, Petri-2 et al. teach a process of solvent evaporation to obtain the dried fermentation broth (para 0107, line 5), which comprises concentrating the fermentation broth through solvent evaporation in view of the fact that liquid solvent in fermentation broth must be evaporated before it becomes dried. Furthermore, Petri-2 et al. expressively teach a step of concentrating the fermentation broth by solvent evaporation to obtain a concentrate of fermentation broth, after the cell separation and before the concentrate is further dried (page 6/right col/last 10 lines, para 0086/lines 4-5 from bottom). Thus, carrying out solvent evaporation, after cell separation, 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.
Regarding Claims 77-79, Petri-2 et al. teach adding carriers/substances to the fermentation broth before starting the drying processes, as indicated above. Petri-2 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 0086, lines 1-2 and 4-6). It is noted that the limitation “to preserve enzymes” in Claim 77 is directed to the intended use and it does not further limit the structure of the recited substances. Therefore, the teachings of Petri-2 et al. renders the claims 77-78 obvious. Regarding the additional limitation in claim 79, Petri-2 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 0075, lines 2-4), to be administered to an animal in need of treatment and protection (para 0069). Petri-2 et al. are silent about a specific amount of a carrier added to the pre-dried fermentation broth. However, it is considered that the amount of Petri-2 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 79 would be obvious over the teachings of Petri-2 et al. in the absence of any showing of unexpected results or criticality.
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 88 is rejected under 35 U.S.C. 103 as being unpatentable over Petri-2 et al. (US 2021/0228653, 2021, effective filing date: May 24, 2017, cited in IDS), as applied to Claims 74, 77-81, 83, and 87, further in view of Zhang et al. (International Journal of Food Properties, 2014, 17:1237–1253, of record).
US 2021/0228653 is equivalent to WO 2017/207371 (published on Dec. 7, 2017). Accordingly, the instant claims are also rejected under 35 U.S.C. 103 over Petri-2 et al. (WO 2017/207371) in view of Zhang et al. All citations are made to US 2021/0228653.
The teachings of Petri-2 et al. are described above.
Regarding the claim 88, Petri-2 et al. do not expressively teach applying a rotary evaporator for concentrating the fermentation broth through solvent evaporation. However, Petri-2 et al. teach applying a conventional evaporation process for concentrating the fermentation broth.
Zhang et al. teach a highly similar method for producing a dried cell-free fermentation broth of Bacillus bacterium, comprising: preparing a fermentation medium (peanut meal); culturing a Bacillus subtilis strain by inoculating it in the peanut meal to obtain a fermentation broth (i.e. fermented peanut meal); 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 the method of Petri-2 et al. and to all the steps in instant claims 74 and 87-88.
It would have been obvious to apply a rotary evaporator in the method of Petri-2 et al. for concentrating through solvent evaporation the cell-free fermentation broth of Bacillus bacterium DSM 32314, 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 the conventional evaporation process used in the method of Petri-2 et al. for concentrating the fermentation broth encompasses a rotary evaporator-based evaporation process. Furthermore, the solvent evaporation using a rotary evaporator is a conventional solvent-evaporation process commonly used in the art for concentrating fermentation broth, as supported by Zhang et al.; and Zhang et al. demonstrate that the rotary evaporator is effective at removing solvent through evaporation from 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-2 et al. because both the method of Zhang et al. and method of Petri-2 et al. are directed to preparation of a dried fermentation broth through concentrating cell-free fermentation broth and then drying the concentrated cell-free fermentation broth; and the rotary evaporator of Zhang et al. is readily applicable to the method of Petri-2 et al. for solvent evaporation
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 75 and 86 are rejected under 35 U.S.C. 103 as being unpatentable over Petri-2 et al. (US 2021/0228653, 2021, effective filing date: May 24, 2017, cited in IDS), as applied to Claims 74, 77-81, 83, and 87, 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, of record).
US 2021/0228653 is equivalent to WO 2017/207371 (published on Dec. 7, 2017). Accordingly, the instant claims are also rejected under 35 U.S.C. 103 over Petri-2 et al. (WO 2017/207371) in view of Diaz. All citations are made to US 2021/0228653.
The teachings of Petri-2 et al. are described above.
Regarding the claims 75 and 86, Petri-2 et al. do not teach cultivating Bacillus amyloliquefaciens CECT-5940 in the culturing step for preparing the dried cell-free fermentation broth. However, Petri-2 et al. teach applying additional probiotics for preparing fermentation broth of their invention (para 0090/line 6) and including extracellular enzymes of Bacillus in their preparation.
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 probiotic B. amyloliquefaciens CECT-5940 in the cultivating step of the method of Petri-2 et al. for obtaining a cell-free fermentation broth comprising CECT-5940 combined with B. licheniform DSM 32314 and/or B. subtilis DSM 32315, or a cell-free fermentation broth preparation of CECT-5940 to be combined with the fermentation broth preparation of DSM 32314 and/or DSM 32315 for being used as a probiotic ingredient in animal feed for controlling pathogenic bacteria in animals/poultry and improving their health. One of ordinary skill in the art would have been motivated to do so, because Petri-2 et al. expressively teach applying additional probiotics for preparing their fermentation broth (as a feed additive). Furthermore, it is well known in the art that B. amyloliquefaciens CECT-5940 is a probiotic bacterium that generates a cell-free fermentation broth having 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 of poultry, 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-2 et al. for improving growth-promotion 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, as supported by Diaz.
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 74, 76-84, and 87 are rejected under 35 U.S.C. 103 as being unpatentable over Pelzer et al. (US 2020/0113952, 2020, effective filing date: June 30, 2017, cited in IDS).
US 2020/0113952 is equivalent to WO 2019/002471 (published on Jan. 3, 2019, effective filing date: June 30, 2017). Accordingly, the instant claims are also rejected under 35 U.S.C. 103 over Pelzer et al. (WO 2019/002471). All citations are made to US 2020/0113952.
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). The further teachings of Pelzer et al. (paras 0124-0126, 0129, and 0159; examples) reveal a method for producing a dried cell-free fermentation broth of B. subtilis DSM 32540, comprising: culturing DSM 32540 in a fermentation medium to obtain a fermentation broth containing DSM 32540; separating microbial cells from the fermentation broth, by centrifuging and/or filtering and removing cells from the fermentation broth, to obtain a cell-free fermentation broth (supernatant) (cell-free liquid portion of the fermentation broth); and drying the resulting fermentation broth/supernatant with or without addition of carriers by a conventional process such as spraying drying, freeze drying, or evaporation; wherein a cell-free supernatant of the fermentation broth is a preferred preparation; and the cell-free fermentation broth comprises metabolites, enzymes and peptides, which are secreted by the cells into the surrounding medium; and the supernatant of the cell cultures comprises a mixture of these compounds. Pelzer et al. teach the 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, B. licheniform DSM 32314, and/or B. subtilis DSM 32539 can be included as additional probiotic along with DSM 32540 for preparing the fermentation broth for feeding animals/poultry (para 0112, lines 1-14).
Regarding the limitation “separating at least 99% of the microorganisms … the amount of cells … is below 1 wt%” in the steps (b) and (c) of claim 74 as well as the further limited cell amounts “below 0.1 wt%” and “below 0.005 wt%” in claims 80 and 81, Pelzer et al. do not expressively teach a specific amount of cells to be removed from the fermentation broth or a specific amount of cells remained in the dried fermentation broth/supernatant. However, Pelzer 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 Pelzer 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 of Pelzer et al. 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 DSM 32540 through centrifugation and/or filtration in the method of Pelzer 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%, 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 dried fermentation broth having cells in the claimed ranges would be obvious over the teachings of Pelzer et al., in the absence of evidence of criticality.
Regarding the limitations about inhibiting C. perfringens and/or S. suis and reducing ANFs in feed recited at the end of the claim 74, Pelzer et al. teach that their fermentation broth inhibits growth of pathogenic bacteria C. perfringens and S. suis. Pelzer et al. are silent about its effect on reducing or eliminating ANFs in a feed. However, the claimed limitations are directed to properties, rather than structures, of the fermentation broth produced by the claimed method. Pelzer et al. suggest a fermentation broth having all the structural limitations of the dried fermentation broth recited in Claim 74. 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 Pelzer et al. meet the requirement of the claimed limitations.
Regarding the limitations about concentrating the fermentation broth in the claims 74 and 87, Pelzer et al. teach a process of solvent evaporation to obtain the dried fermentation broth, which comprises concentrating the fermentation broth through solvent evaporation in view of the fact that liquid solvent in fermentation broth must be evaporated before it becomes dried. Furthermore, Pelzer et al. expressively teach a step of concentrating the fermentation broth by solvent evaporation to obtain a concentrate of fermentation broth, after the cell separation and before the concentrate is further dried (para 0124/last 8 lines, para 0125/lines 1-3 and 5). Thus, carrying out solvent evaporation, after cell separation, 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.
Regarding Claims 77-79, Pelzer et al. teach adding carriers/substances to the fermentation broth before starting the drying processes, as indicated above. Pelzer et al. further teach that suitable carriers/substances are selected from anti-caking agents, anti-oxidation agents, bulking agents, and/or protectants for improving recovery or efficiency or physical properties (para 0103). It is noted that the limitation “to preserve enzymes” in Claim 77 is directed to the intended use and it does not further limit the structure of the recited substances. Therefore, the teachings of Pelzer et al. render the claims 77-78 obvious. Regarding the additional limitation in claim 79, Pelzer 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 0104/line 7), to be administered to an animal in need of treatment and protection. Pelzer et al. are silent about an amount of a specific carrier substance added to the fermentation broth preparation. However, it is considered that the amount of Pelzer 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 79 would be obvious over the teachings of Pelzer et al. in the absence of any showing of unexpected results or criticality.
Regarding the claims 76, 83, and 84, Pelzer et al. teach further applying B. subtilis DSM 32315, B. licheniform DSM 32314, and/or B. subtilis DSM 32539 in addition to the DSM 32540 for preparing the fermentation broth. It would have been obvious to further cultivate probiotic B. subtilis DSM 32315, B. licheniform DSM 32314, or B. subtilis DSM 32539 in the cultivating step of the method of Pelzer et al. for obtaining a cell-free fermentation broth preparation comprising DSM 32315, 32314, or 32539 to be combined with the fermentation broth preparation of B. subtilis DSM 32540, or obtaining a cell-free fermentation broth comprising DSM 32315, 32314, or 32539 combined with DSM 32540 for preparing a probiotic ingredient to be added to animal feed for controlling pathogenic bacteria in animals/poultry and improving their health.
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 76, 82, and 84 are rejected under 35 U.S.C. 103 as being unpatentable over Petri-2 et al. (US 2021/0228653, 2021, effective filing date: May 24, 2017, cited in IDS), as applied to Claims 74, 77-81, 83, and 87, further in view of Pelzer et al. (US 2020/0113952, 2020, effective filing date: June 30, 2017, cited in IDS).
US 2021/0228653 is equivalent to WO 2017/207371 (published on Dec. 7, 2017); and US 2020/0113952 is equivalent to WO 2019/002471 (published on Jan. 3, 2019, effective filing date: June 30, 2017). Accordingly, the instant claims are also rejected under 35 U.S.C. 103 over Petri-2 et al. (WO 2017/207371) in view of Pelzer et al. (WO 2019/002471). All citations are made to US 2021/0228653 and US 2020/0113952.
The teachings of Petri-2 et al. and Pelzer et al. are described above.
Regarding the claims 76, 82, and 84, Petri-2 et al. do not teach cultivating Bacillus subtilis DSM 32540 or Bacillus pumilus DSM 32539 for preparing the dried fermentation broth.
It would have been obvious to further cultivate probiotic Bacillus subtilis DSM 32540 or Bacillus pumilus DSM 32539 in the method of Petri-2 et al. for obtaining a cell-free fermentation broth comprising DSM 32540 or 32539 combined with B. licheniform DSM 32314 and/or B. subtilis DSM 32315, or obtaining a cell-free fermentation broth preparation of DSM 32540 or 32539 to be combined with the fermentation broth preparation of DSM 32314 and/or 32315 of Petri-2 et al. for being used as a probiotic ingredient in animal feed for controlling pathogenic bacteria in animals/poultry and improving their health. One of ordinary skill in the art would have been motivated to do so, because Petri-2 et al. expressively teach further applying additional Bacillus probiotics for preparing their fermentation broth (as a feed additive); and B. subtilis DSM 32540 and B. subtilis DSM 32539 are Bacillus probiotics known in the art, as supported by Pelzer et al. Furthermore, it is known in the art that cell-free fermentation broth of B. subtilis DSM 32540 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, as supported by Pelzer et al. Moreover, it is known in the art that a combination of probiotics B. licheniform DSM 32314, B. subtilis DSM 32315, B. subtilis DSM 32540, and/or B. subtilis DSM 32539 (as feed additive) provides health benefits to animals/poultry, as supported by Pelzer et al. One of ordinary skill in the art has a reasonable expectation of success at modifying the method of Petri-2 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. subtilis DSM 32540 or B. pumilus DSM 32539 to B. licheniform DSM 32314 and/or B. subtilis DSM 32315 of Petri-2 et al. is expected to further improve effect of inhibiting pathogenic bacteria related to animals/poultry, as supported by Pelzer et al.
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 76, 82, and 84-85 are rejected under 35 U.S.C. 103 as being unpatentable over Petri-2 et al. (US 2021/0228653, 2021, effective filing date: May 24, 2017, cited in IDS), as applied to Claims 74, 77-81, 83, and 87, further in view of Pelzer-2 et al. (WO 2019/038153, 2019, effective filing date: Aug. 24, 2017, cited in IDS).
US 2021/0228653 is equivalent to WO 2017/207371 (published on Dec. 7, 2017). Accordingly, the instant claims are also rejected under 35 U.S.C. 103 over Petri-2 et al. (WO 2017/207371) in view of Pelzer-2 et al. All citations are made to US 2021/0228653.
The teachings of Petri-2 et al. are described above.
Regarding the claims 76, 82, and 84-85, Petri-2 et al. do not teach cultivating B. subtilis DSM 32540, B. pumilus DSM 32539, or B. subtilis DSM 32592 for preparing the dried fermentation broth.
Pelzer-2 et al. teach Bacillus subtilis DSM 32592 is a probiotic strain with strong inhibition of swine and poultry related pathogens, and also teach a preparation of DSM 32592 used as a probiotic agent in feed product for inhibiting pathogens including C. perfringens, C. difficile, S. gallinaceus, S. suis, C. coli, C. jejuni and E. cecorum, (abstract, page 1/lines 17-33, page 5/lines 19-27), wherein the preparation is a cell-free fermentation broth of B. subtilis DSM 32592, produced by centrifuging and/or filtrating a fermentation broth obtained from culturing the DSM 32592 in a fermentation medium, followed by removing microbial cells from the fermentation broth to obtain the cell-free fermentation (i.e. supernatant), 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 (page 17: lines 9-13 and 18-38); and the fermentation broth is then dried with or without addition of carriers by using conventional drying processes such as spray drying, freeze drying, or evaporation (page 17, lines 24-28); wherein the fermentation broth preparation is added to feed or food products for improving health of animals such as poultry (page 11/lines 12-20, page 12/lines 12-14, page 13/lines 1-11). Petri-2 et al. further teach applying additional probiotics for preparing fermentation broth, which preferably comprise B. pumilus DSM 32539, B. subtilis DSM 32540, B. subtilis DSM 32315, and B. licheniformis DSM 32314 (plage 15/lines 5-12).
It would have been obvious to try to further cultivate B. subtilis DSM 32592, B. subtilis DSM 32540, or B. pumilus DSM 32539 in the cultivation step of the method of Petri-2 et al. for obtaining a cell-free fermentation broth comprising DSM 32592, 32540, 32539 combined with B. licheniform DSM 32314 and/or B. subtilis DSM 32315 of Petri-2 et al., or obtaining a cell-free fermentation broth preparation of DSM 32592, 32540, 32539 to be combined with the cell-free fermentation broth preparation of B. licheniformis DSM 32314 as a probiotic ingredient in feed product for controlling pathogenic bacteria in animals/poultry and improving their health, as taught by Pelzer-2 et al. One of ordinary skill in the art would have been motivated to do so, because Petri-2 et al. teach further applying additional Bacillus probiotics for preparing their fermentation broth preparation (as a feed additive); and B. subtilis DSM 32540, B. pumilus DSM 32539, B. subtilis DSM 32592 are all probiotic bacteria, just like B. subtilis DSM 32315 and DSM 32314 taught by Petri-2 et al. Furthermore, these additional probiotics strongly inhibit pathogenic bacteria in animals/poultry, including C. perfringens, S. suis, C. difficile, S. gallinaceus, C. coli and E. cecorum, as supported by Pelzer-2 et al. Moreover, it is known in the art that a combination of probiotics B. subtilis DSM 32592, B. licheniform DSM 32314, B. subtilis DSM 32315, B. subtilis DSM 32540, and/or B. subtilis DSM 32539 (as feed additive) provides health benefits to animals/poultry, as supported by Pelzer-2 et al. One of ordinary skill in the art has a reasonable expectation of success at modifying the method of Petri-2 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. subtilis DSM 32592, B. subtilis DSM 32540, or B. pumilus DSM 32539 to B. licheniform DSM 32314 and/or B. subtilis DSM 32315 of Petri-2 et al. is expected to further improve effect of inhibiting pathogenic bacteria related to animals/poultry, as supported by Pelzer-2 et al.
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 objection to claim 73 and the rejection of claims 62-63 under 35 USC 112(d) in the response filed on 03/29/2026 (pages 5-6) have been fully considered but they are moot because they have been withdrawn for the reasons indicated above.
Applicant's arguments about the rejections of claim 42 under 35 USC 103 over Petri in the 03/29/2026 response (pages 6-9) have been fully considered, but they are moot because the 103 rejections of record have been withdrawn, and the ground of the rejections in this office action is different from that in the previous office action. As indicated in the 103 rejections above, Petri-2 et al. specifically teach B. licheniform DSM 32314 recited in the new claim 74, and a method of producing a dried cell-free fermentation broth of DSM 32314, which renders the newly submitted claims to be obvious.
In response to Applicant’s arguments based on ANF inhibition in page 7 of the response, it is noted that the claim 74 recites culturing, separating, and drying steps for generating a dried fermentation broth, but the claim does not recite any limitations to define concentrations or amounts of active components in the dried fermentation broth. The ANF inhibition is directed to an inherent feature of the dried fermentation broth, and this feature would have been obvious over the teachings of Petri-2 et al. for the reasons indicated above (see details in page 6).
Applicant’s arguments based on Zhang in the response (pages 7 and 8) have been fully considered but they are not persuasive. Examiner notes that the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). As such, the test for obviousness in the instant case is not based on whether the features of fermentation preparation from peanut meal medium taught by the secondary reference Zhang may be bodily incorporated into a probiotic animal feed taught by Petri-2, or the claimed invention must be expressly suggested in both Petri-2 and Zhang. Rather, the test is what the combined teachings of Petri-2 and Zhang would have suggested to those of ordinary skill in the art. As indicated above, Petri-2 et al. teach applying a conventional evaporation process for concentrating their fermentation broth; and Zhang demonstrates that an evaporation process based on a rotary evaporator is a conventional evaporation process that can effectively concentrate fermentation broth through solvent evaporation. As such, in view of combined teachings of Petri-2 and Zhang, it would have been obvious to those of ordinary skill in the art to apply the rotary evaporator taught by Zhang to concentrate the fermentation broth through solvent evaporation in the method of Petri-2 for obtaining a concentrated fermentation broth.
In response to Applicant’s arguments about routine optimization in the response (page 9), it is noted that Petri-2 newly cited in the 103 rejections above does teach the microbial strain, B. licheniform DSM 32314, specifically recited in the new claims 74. No “routine optimization” is involved for Petri-2 to meet the claimed limitations about amended microbial strain and ANF reduction.
Overall, the conclusion of the obviousness of the new claims 74-88 has been established for all the reasons indicated above.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
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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
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656
Prosecution Insights