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 .
Status of Claims
Receipt of Arguments/Remarks filed on 2/17/2026 is acknowledged. Claims 1-21 are pending. Claims 1, 6-7, and 20 were amended. Claims 10-17, 19, and 21 are withdrawn from consideration as being directed to a nonelected invention.
Withdrawn Rejections
The rejection of claim 5 under 35 U.S.C. § 112(a) is withdrawn in view of the statement under 37 C.F.R. 1.808 and deposit receipts filed 2/17/2026.
The rejection of claims 6, 7, and 20 under 35 U.S.C. § 112(b) is withdrawn in view of claim amendments.
The rejections on the grounds of nonstatutory double patenting are withdrawn in view of claim amendments.
New and modified rejections necessitated by amendment
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-7, 18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over da Silva et al., Lwt; 90:412-7 in view of Fang et al., Food Hydrocolloids; 93:102-10 (cited in IDS 3/14/2023); Călinoiu et al., Coatings; 9(3):194; and Cortés et al., Cereal Chemistry; 91(3):300-8.
Regarding claim 1, da Silva teaches a microencapsulated microbial culture comprising Bifidobacterium lactis BB-12 (da Silva p. 412 para. 2). da Silva teaches that probiotics are defined as live microorganisms (da Silva p. 412 para. 1). da Silva teaches that the probiotic bacteria are sensitive to oxygen, i.e. anaerobic, and teaches anaerobic growth (da Silva p. 412 para. 3; p. 413 Section 2.8). Thus, da Silva teaches a microencapsulated microbial culture, comprising a live encapsulated anaerobic microbial culture.
da Silva teaches that the microcapsule is produced by complex coacervation using a first coacervate component, gelatin, and a second coacervate component, gum Arabic (da Silva “Abstract”; pg. 413 Section 2.4). da Silva teaches that coacervation involves combining two oppositely-charged hydrocolloid solutions to cause interaction and precipitation of complex polymers, which presents advantages such as high encapsulation efficiency, control of particle size, possibility of working with biopolymers, absence of organic solvents, low cost and soft conditions of processing (da Silva pg. 412-413 para. 3). Further, microcapsules produced by coacervation are versatile and have excellent controlled release characteristics modulated by changes in ionic strength, pH and temperature (da Silva pg. 413 first partial para.).
Regarding claims 2 and 3, da Silva teaches that the microencapsulated microbial culture is a lactic acid bacterium from the genus Bifidobacterium, Bifidobacterium lactis BB-12 (da Silva pg. 412 para. 2).
Regarding claim 4, da Silva teaches that the microbial culture is a probiotic (da Silva pg. 412 para. 1-2).
Regarding claim 5, da Silva teaches that the microbial culture is Bifidobacterium lactis BB-12 (da Silva pg. 412 para. 2). BB-12 is also known as Bifidobacterium animalis subsp. lactis deposited as DSM 15954 (see instant specification pg. 7).
Regarding claim 7, da Silva teaches adding 1 g of probiotic culture to 100 mL of 2.5% (or 2.5 g/100 mL) gelatin, then additionally adding 100 mL of 2.5% gum Arabic and 400 mL of distilled water (da Silva pg. 413 Section 2.4). Therefore, the ratio of both matrix components (2.5 g gelatin and 2.5 g gum Arabic = 5 g) to microbial culture (1 g) is 5:1, or 5. When claimed ranges "overlap or lie inside the ranges disclosed by the prior art" and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See MPEP 2144.05(I). It is noted that "where 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 2144.05(II).
da Silva does not teach that the first and second coacervate components are chosen from octenyl succinic anhydride (OSA) starch and chitosan as recited in claim 1 or the ratio of OSA to chitosan as recited in claims 6 and 20.
Regarding claim 1, Fang teaches microencapsulation of β-carotene in OSA starch and chitosan (Fang “Abstract”). Fang teaches that OSA starch has been successfully used for emulsification, encapsulation, films and coatings, and gel formation, and has great advantages as both an emulsifier and a thickening agent, very good tolerance to harsh environmental conditions via steric stabilization and can protect natural ingredients against oxidation and/or process digestion (Fang pg. 103 first full para.). Fang teaches OSA starch has a negative charge and can interact with positively charged polymers such as chitosan to form a secondary layer, making it easy to form multilayer emulsions (Fang pg. 103 first full para.).
Regarding claim 1, Calinoiu teaches chitosan-based microencapsulation of live probiotic cultures, including Bifidobacterium animalis (Calinoiu Abstract; pp. 6-7 para. 5). Calinoiu teaches that food-grade coatings like biopolymers including chitosan and starch are the most suitable materials for bacterial microencapsulation due to their high protective rate under certain stress conditions and their availability, low-cost, and biocompatibility (Calinoiu pp. 2-3 Section 2 para. 2). Calinoiu teaches that the main advantages of chitosan coating are unique cationic character, high biocompatibility, non-toxicity, and biodegradability (Calinoiu p. 4 Section 3 para. 1). Caliniou teaches coacervation as a technique for microencapsulation of probiotics (Calinoiu p. 7 Section 3.3. para. 3).
Regarding claim 1, Cortes teaches microencapsulation of Lactobacillus and Bifidobacterium live probiotic cultures using modified starch (Cortes p. 300 para. 1-3). Cortes teaches encapsulating bacteria with starch octenyl succinates, or OSA starch (Cortes p. 303 para. 1). Cortes teaches that starch derivatives have demonstrated a high degree of solubility, limited viscosity in solution, good emulsifying properties, and good drying properties (Cortes p. 300 para. 3). Cortes teaches that introduction of hydrophobic groups in OSA-modified starches at low DS levels confers some hydrophobic properties to starch (Cortes p. 304 para. 1). Cortes teaches that succinylated and acetylated starch conferred the best probiotic survival and are applicable for encapsulation of probiotics (Cortes p. 307 Conclusions).
It would have been obvious for a skilled artisan to modify the teachings of da Silva and utilize OSA starch and chitosan as the complex coacervate components to microencapsulate a live, anaerobic microbial culture. da Silva teaches complex coacervation of live Bifidobacterium, which is anaerobic, and teaches that coacervation involves electrostatic interaction between two oppositely-charged polymers. Fang teaches that OSA starch and chitosan are oppositely charged polymers that can interact and can be used for encapsulation. Given the teachings of Caliniou and Cortes that chitosan and OSA starch are both suitable and beneficial polymers for encapsulation of live probiotics, it would have been obvious to a skilled artisan that the components used by da Silva could be substituted with OSA starch and chitosan for microencapsulation of live Lactobacillus.
A person of ordinary skill in the art would have been motivated to make this substitution because food-grade coatings like biopolymers including chitosan and starch are the most suitable materials for bacterial microencapsulation due to their high protective rate under certain stress conditions and their availability, low-cost, and biocompatibility, and chitosan has many advantages including unique cationic character, high biocompatibility, non-toxicity, and biodegradability (Calinoiu pp. 2-3 Section 2 para. 2; p. 4 Section 3 para. 1). OSA starch additionally has advantageous properties such as a high degree of solubility, limited viscosity in solution, good emulsifying properties, and good drying properties, and can be used for encapsulation of live probiotics (Cortes p. 300 para. 3). Thus, a skilled artisan would have been motivated to substitute the components of the complex coacervate taught by da Silva with OSA starch and chitosan, which both have specific benefits for encapsulation of probiotic cultures, in a complex coacervate, a technique which has advantages including high encapsulation efficiency, control of particle size, possibility of working with biopolymers, absence of organic solvents, low cost and soft conditions of processing (da Silva pg. 412-413 para. 3). As Fang teaches that OSA starch and chitosan are oppositely charged and interact for encapsulation, and are thus suited for complex coacervation which requires interaction of oppositely charged polymers, a skilled artisan would have been motivated to use these components which are beneficial and suitable for live probiotic encapsulation in a complex coacervate.
A skilled artisan would have had a reasonable expectation of success in making this substitution because it is known that OSA starch and chitosan can interact and be used for encapsulation as taught by Fang, and it is further known that chitosan and OSA starch are beneficial and suitable for live probiotic encapsulation as taught by Calinoiu and Cortes. Thus, a skilled artisan could reasonably expect success in substituting these components in the complex coacervate of da Silva.
Regarding claims 6 and 20, Fang teaches an optimized emulsion layer comprising 4.6 wt% OSA starch and 0.3 wt% chitosan (Fang pg. 105 Section 3.2 para. 2). Thus, the ratio of OSA to chitosan is 4.6:0.3, or 15.33:1. Claim 6 recites a ratio of OSA to chitosan of between 75:25 (or 3:1) and 98:2 (or 49:1). Claim 20 recites a ratio of OSA to chitosan of between 85:15 (or 5.67:1) and 95:5 (or 19:1). The ratio of OSA to chitosan taught by Fang is therefore within these ranges. When claimed ranges "overlap or lie inside the ranges disclosed by the prior art" and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See MPEP 2144.05(I).
Based on the teachings of Fang, a skilled artisan would be aware that OSA starch and chitosan can interact and form multilayer emulsions using OSA starch:chitosan ratios within the claimed range. Further, the amounts and concentrations of OSA starch and chitosan used would have been routinely optimized by a skilled artisan based on the other assay conditions. Fang teaches using various concentrations of chitosan and OSA starch to optimize the amounts needed for the specific desired product and to achieve the desired electrostatic interactions (Fang p. 103 Sections 2.2 and 2.3). This means the concentrations of OSA starch and chitosan are result-effective variables. Result-effective variables would be optimized through routine experimentation by one having ordinary skill in the art. Thus, it would have been obvious for a person having ordinary skill in the art, through routine experimentation, to arrive at concentrations and ratios within the claimed range. Furthermore, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144.05(II)(A).
Regarding claim 18, the limitation “obtained by a method according to claim 13” is a product-by-process limitation, and as such patentability is assessed based on the structure implied by the steps, not the manipulations of the recited steps. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)” (see MPEP § 2113 subsection I). The structure of claim 18 is a microencapsulated microbial culture according to claim 1. Therefore, any prior art that teaches this structure reads on claim 18. As da Silva, Fang, Calinoiu, and Cortes teach a microencapsulated microbial culture according to claim 1, the product of claim 18 is obvious in view of these references.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over da Silva, Fang, Calinoiu, and Cortes as set forth above regarding claims 1-7, 18, and 20, and further in view of Cui et al., Archives of pharmacal research; 29(8):707-11.
da Silva, Fang, Calinoiu, and Cortes teach the microencapsulated microbial culture of claim 1, as set forth above. These references do not teach that one or both of the first or second matrix components further comprises an antioxidant as recited in claims 8 and 9.
Regarding claims 8 and 9, Cui teaches Bifidobacteria-loaded alginate poly-l-lysine microparticles to preserve the viability and stability of bifidobacteria during storage (Cui pg. 707 “Abstract”; para. 1-2). Cui teaches that antioxidants are essential for preventing oxidation because anaerobic microorganisms such as Bifidobacterium lose viability when exposed to air, and antioxidants are commonly added to pharmaceutical compositions to decrease oxidation (Cui pg. 710 para. 2). Cui teaches adding the antioxidant ascorbic acid (or Vitamin C) to the microparticle formulation, resulting in significantly increased viability of the Bifidobacterium in the microparticles (Cui “Abstract”; Table I; pg. 710 para. 2).
It would have been obvious to a skilled artisan, before the effective filing date, to combine the teachings of these references, arriving at a microencapsulated microbial culture further comprising an antioxidant such as Vitamin C. All of these references are directed to encapsulation techniques. As Cui teaches that antioxidants can be added to a Bifidobacterium microparticle to decrease oxidation, it would have been obvious that an antioxidant component could similarly be added to a microencapsulated Bifidobacterium as taught by da Silva for the same purpose of reducing oxidation and enhancing bacterial viability.
A person of ordinary skill in the art would have been motivated to modify the microencapsulated microbial culture taught by da Silva, Fang, Calinoiu, and Cortes to include an antioxidant such as Vitamin C for the purpose of decreasing oxidation, which can result in loss of culture viability for anaerobic bacteria such as Bifidobacterium (Cui pg. 710 para. 2). It would therefore be considered advantageous to add an antioxidant to the encapsulated culture to preserve bacterial viability over time.
A skilled artisan would have a reasonable expectation of success in making this combination to create a microencapsulated microbial culture comprising an antioxidant such as Vitamin C, given the teachings of Cui that ascorbic acid added to a Bifidobacterium-incorporated microparticle results in enhanced viability of Bifidobacterium. A skilled artisan could reasonably expect success in adding such an antioxidant to the microencapsulated culture of da Silva, Fang, Calinoiu, and Cortes for this same purpose of enhancing bacterial viability by reducing oxidation.
Response to Arguments
In light of amendments to the claims, the rejection of claims 1-7, 18, and 20 under 35 U.S.C. § 103 in view of da Silva and Fang has been withdrawn. However, upon further consideration, new grounds of rejection of claims 1-7, 18, and 20 are made under 35 U.S.C. § 103 in view of da Silva, Fang, Calinoiu, and Cortes as set forth above. Responses to relevant arguments regarding prior art are set forth below.
Applicant argues that the person of skill in the art would find no teaching or motivation to combine da Silva and Fang with operable/predictable results, as the types of encapsulation are materially different. Applicant argues that Fang’s system is incompatible with live probiotic encapsulation as it's optimized for hydrophobic molecules like β-carotene, not for biological viability and would destroy or severely damage live probiotics. Applicant argues that chitosan is known to have antimicrobial activity, and would be expected to harm Bifidobacteria.
In response to this argument, it is the position of the examiner that a skilled artisan could reasonably expect success in using OSA starch and chitosan as the coacervate components in place of the components taught by da Silva. da Silva teaches that complex coacervation requires electrostatic interaction of two oppositely-charged polymers (see da Silva Introduction). Fang teaches that OSA starch and chitosan are oppositely-charged polymers capable of electrostatic interaction (see Fang p. 103). Thus, while Fang’s method of encapsulation differs from the complex coacervation method of da Silva, a skilled artisan would have recognized that OSA starch and chitosan have the properties required for complex coacervation, and would have been motivated to utilize these components due to the benefits of OSA starch and chitosan for probiotic encapsulation as discussed in the above rejection. Fang is relied upon to teach that OSA starch and chitosan are oppositely charged polymers that undergo electrostatic interactions and have use in encapsulation, to provide a reason to use these components in a complex coacervation technique as taught by da Silva.
Regarding the incompatibility with live probiotic encapsulation and the antimicrobial activity of chitosan, Calinoiu teaches that chitosan is beneficial and suitable for encapsulation of live probiotics, and thus a skilled artisan could expect success in using chitosan for this purpose in a complex coacervation technique.
Applicant argues that da Silva teaches away from the Office's proposed substitution, as da Silva demonstrates high encapsulation efficiency and excellent probiotic survival using gelatin and gum arabic, and thus a skilled artisan would have no motivation to abandon an already proven, probiotic-compatible system in favor of a nanoemulsion approach designed for lipophilic actives.
In response to this argument, it is again noted that Fang is relied upon to teach the properties of OSA starch and chitosan, showing that these are oppositely charged polymers that could undergo electrostatic interaction as required for complex coacervation. Further, a skilled artisan would have been motivated to substitute the gelatin and gum Arabic of da Silva for OSA starch and chitosan because biopolymers including chitosan and starch are the most suitable materials for bacterial microencapsulation due to their high protective rate under certain stress conditions and their availability, low-cost, and biocompatibility, and chitosan has many unique advantages (Calinoiu pp. 2-3 Section 2 para. 2; p. 4 Section 3 para. 1). OSA starch additionally has advantageous properties such as a high degree of solubility, limited viscosity in solution, good emulsifying properties, and good drying properties, and can be used for encapsulation of live probiotics (Cortes p. 300 para. 3). Given the advantages of complex coacervation, i.e. high encapsulation efficiency, control of particle size, possibility of working with biopolymers, absence of organic solvents, low cost and soft conditions of processing (da Silva pg. 412-413 para. 3), a skilled artisan would have been motivated to substitute the components of the complex coacervate taught by da Silva with OSA starch and chitosan, which are both known to have specific benefits for encapsulation of probiotic cultures.
Applicant argues that the antioxidants in Cui address oxygen permeability specific to that system, but as complex coacervates already provide inherent protection, there would be no
motivation for the skilled artisan to further add antioxidants.
In response to this argument, it is the position of the examiner that due to the known use of antioxidants such as vitamin C for preventing oxidation with anaerobic microorganisms such as Bifidobacterium, it would have been obvious to include such a component. It would be considered beneficial to include an antioxidant in one or both of the complex coacervate components to provide specific protection against oxidation which is a known issue for probiotics like Bifidobacterium, even if complex coacervates do provide some protection. For example, in the method of da Silva for coacervation, the bacteria are added to the first coacervate component and stirred before adding the second coacervate component (da Silva p. 413 Section 2.4). Therefore, it would be advantageous to include an antioxidant with the first coacervate component, as the probiotic is added before the complex coacervate has formed.
Conclusion
Claims 1-9, 18, and 21 are rejected. No claims are allowed.
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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
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/EMILY F EIX/Examiner, Art Unit 1653
/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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