DETAILED ACTION
Claims 40-45 and 48-63 are pending and under consideration on the merits.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/20/2026 has been entered.
Status of the Rejections
The 112(b) rejection is withdrawn in view of the amendment.
The 103 rejections are withdrawn in view of the amendment and replaced with new rejections incorporating the teachings of a new reference, Sygmund et al.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 40-42, 48-52, 56, 60, and 63 are rejected under 35 U.S.C. 103 as unpatentable over Subramaniam et al. (US Pat. Pub. 2004/0032036; of record in IDS) in view of Oudgenoeg et al. (EP 1 169 922; of record in IDS) and Sygmund et al. (Microbial Cell Factories 2013, 12:38).
As to claims 40-42, 48-49, 51-52, and 60, Subramaniam discloses a method for encapsulating a core material such as a flavor agent or perfume comprising contacting the flavor agent with a heteropolymer obtained by cross-linking a protein comprising an aromatic amino acid such as albumin with a plant extract comprising a phenolic compound (claim 51) and an anionic polymer such as alginate (claim 52) having the ability to phase separate from the heteropolymer to obtain a continuous phase and a dispersed phase comprising the heteropolymer particles (claim 42) which encapsulate the core material, wherein the phase separation is coacervation (claim 41)(paragraphs 12, 18-20, 26-28, 30, 37, and claims 1, 3, and 6-8 of Subramaniam).
Regarding claims 49, the protein may be albumin or gelatin (an “animal protein”)(paragraph 28).
As to claim 60, the heteropolymer particles may be incorporated into a pharmaceutical or cosmetic product and may be used to encapsulate materials other than a flavor agent (paragraph 33).
As to claims 40-42, 48-49, 51-52, and 60, Subramaniam does not further expressly disclose an embodiment wherein the encapsulated agent is a bioactive agent as recited by claim 1. Additionally, Subramaniam discloses crosslinking the heteropolymer after coacervation while claim 1 recites that coacervation (i.e., phase separation) occurs after the heteropolymer is crosslinked, and claim 48 specifies that the heteropolymer formation, phase separation, and encapsulation occurs simultaneously. Nor does Subramaniam expressly disclose that the heteropolymer is obtained by contacting the protein with a peroxidase and hydrogen peroxide, and wherein the peroxidase catalyzes the crosslinking of the phenolic compound with the hydrogen peroxide acting as a co-substrate and wherein the hydrogen peroxide is generated along with a corresponding organic acid by a cellobiose oxidase using a carbohydrate substrate, all as recited by claim 40, or that the peroxidase is horseradish peroxidase (claims 56 and 63), or that the protein that is crosslinked is casein (claim 50).
Oudgenoeg discloses a method of enzymatically crosslinking a protein and a polymer comprising a phenolic group (Abstract and paragraph 1), and expressly discloses that casein is a suitable alternative to the use of gelatin as the protein to be crosslinked (paragraph 27). Oudgenoeg further teaches that a peroxidase and preferably horseradish peroxidase may be used as the enzyme and that the enzyme is used in conjunction with an oxidizing agent such as hydrogen peroxide, which can be added or generated in situ by an enzyme such as glucose oxidase and an appropriate substrate (paragraph 25).
Sygmund discloses that cellobiose dehydrogenase has the ability to generate hydrogen peroxide in situ from mono or oligo saccharides such as lactose, which is advantageous compared to oxidases such as glucose oxidase which are limited to monosaccharide substrates (Abstract and page 2, 2nd paragraph).
As to claims 40-42, 48-49, 51-52, and 60, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the method of Subramaniam by selecting a bioactive agent as the agent to be encapsulated, because Subramaniam expressly teaches that the method may be used to encapsulate materials other than a perfume or flavoring agent and may be used, for example, in cosmetic and pharmaceutical compositions, such that the skilled artisan would have had a motivation to use the method to encapsulate a bioactive agent for incorporation into a pharmaceutical composition for delivery of said bioactive agent with a reasonable expectation of success.
It further would have been prima facie obvious to modify the method of Subramaniam by performing the crosslinking of the protein comprising an aromatic amino acid with the phenolic compound as taught by Subramaniam by using horseradish peroxidase and hydrogen peroxide in light of Oudgenoeg’s express teaching that a protein may be crosslinked with a phenolic compound in this manner. Such a modification is merely the substitution of one known element for another according to known methods to obtain predictable results, which is prima facie obvious. MPEP 2143. It further would have been prima facie obvious to use a cellobiose to generate the hydrogen peroxide because Oudgenoeg expressly teaches that an enzyme such as glucose oxidase can be used to generate the hydrogen peroxide in situ instead of adding external hydrogen peroxide and Sygmund teaches that cellobiose also can generate hydrogen peroxide in situ from a carbohydrate substrate and is superior to glucose oxidase for this purpose because it can utilize a wider variety of carbohydrate substrates.
It further would have been prima facie obvious to crosslink the heteropolymer prior to phase separation and to effect the heteropolymer formation, phase separation, and encapsulation simultaneously as recited by claim 23 because any order of performing process steps is prima facie obvious in the absence of new or unexpected results. In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946).
Regarding claim 50, it further would have been prima facie obvious to select a casein as the protein, because Oudgenoeg discloses that casein is a suitable alternative to the use of gelatin as a protein that can be crosslinked with a polymer comprising a phenolic group, such that the skilled artisan reasonably would have expected that casein could be used as the protein used to form the heteropolymer crosslinked with a phenolic compound in the Subramaniam method. Such a modification is merely the simple substitution of one known element for another according to known methods to yield predictable results, which is prima facie obvious. MPEP 2143.
Claims 43-44, 53-55, and 58 are rejected under 35 U.S.C. 103 as unpatentable over Subramaniam et al. (US Pat. Pub. 2004/0032036; of record in IDS) in view of Oudgenoeg et al. (EP 1 169 922; of record in IDS) as applied to claims 40-42, 48-52, 56, 60, and 63 above, and further in view of Lebo, Jr. et al. (US Pat. No. 5,552,149; of record).
The teachings of Subramaniam and Oudgenoeg are relied upon as discussed above, but Subramaniam does not further expressly disclose that the bioactive agent is among those recited by claims 43-44 such as a spore-forming bacterium microorganism as recited by claim 44, nor that the heteropolymer is a sodium caseinate lignosulfonate heteropolymer as recited by claim 53, nor a step of coating the heteropolymer particles with a layer of a protective material (claim 54) such as ethylcellulose or a hydrophobically modified biopolymer (claim 55). Nor does Subramaniam expressly disclose that the average degree of polymerization of the heteropolymer is within the recited range of claim 58.
Lebo, Jr. discloses a method for the microencapsulation of an agriculturally active substance to improve resistance to environmental degradation, such as UV light, via a coacervation process, wherein a sulfonated lignin is used as a UV protectant which is combined with a protein such as gelatin to form the wall of the capsule (Abstract and claim 1), wherein the agriculturally active substance may be a microorganism such as Bacillus Cereus (a bacterium that can form spores)(column 3, last paragraph). The sulfonated lignin is disclosed as typically being in the salt form such as its sodium salt (column 4, 1st full paragraph). Lebo, Jr. also teaches that sulfonated lignins can react with proteins such as gelatin to form a crosslinked compound having low solubility under acidic or neutral conditions but high solubility in alkaline systems (column 2, last paragraph). Lebo, Jr. also teaches that it was known in the prior art to coat UV-sensitive materials with UV protectants such as ethylcellulose (column 1, 5th paragraph).
As to claims 53 and 58, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the method of Subramaniam and Oudgenoeg as combined supra by selecting casein as the protein and a sulfonated lignin as the polymer, because Lebo, Jr. teaches that the use of this combination of protein and polymer in a coacervation process can be used to encapsulate an active agent in a manner that advantageously results in a pH-responsive microcapsule having low solubility under acidic or neutral conditions but high solubility in alkaline systems. The heteropolymer of the resulting composition will possess a degree of polymerization within the scope of claim 58, because it comprises the same protein (casein) and polymer (sulfonated lignin) which the specification teachings will produce a heteropolymer having said degrees of polymerization (paragraphs 101-102 as published). The U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the countless ways that an Applicant may present previously unmeasured characteristics. When the prior art appears to contain the same ingredients that are disclosed by Applicants' own specification as suitable for use in the invention, a prima facie case of obviousness has been established, and the burden is properly shifted to Applicants to demonstrate otherwise. See MPEP 2112.01.
Regarding claims 43-44, it further would have been prima facie obvious to select Bacillus Cereus as the bioactive agent for encapsulation, because Subramaniam does not limit the identity of the encapsulated agent and teaches that the capsules taught therein also may be used in a pharmaceutical formulation to encapsulate an active ingredient, and Lebo, Jr. teaches that microorganisms for delivery such as Bacillus Cereus benefit from being encapsulated in a wall material comprising a protein such as gelatin and a sulfonated lignin which will protect the microorganism from degradation, such that the skilled artisan reasonably would have expected that the Subramaniam method could be used to successfully encapsulate Bacillus Cereus for delivery.
As to claims 54-55, it further would have been prima facie obvious to coat ethylcellulose onto the heteropolymer particles in order to impart additional UV protectant properties to the particles, in light of Lebo, Jr.’s teaching that it was known that such a coating can provide protection against UV radiation.
Claims 45, 57, and 61-62 are rejected under 35 U.S.C. 103 as unpatentable over Subramaniam et al. (US Pat. Pub. 2004/0032036; of record in IDS) in view of Oudgenoeg et al. (EP 1 169 922) as applied to claims 40-42, 48-52, 56, 60, and 63 above, and further in view of Pabst (US Pat. No. 5,902,617; of record).
The teachings of Subramaniam and Oudgenoeg are relied upon as discussed above, but they do not further expressly disclose that the bioactive agent is an enzyme (claim 45), that one or more of the ingredients is sterilized prior to encapsulation of the bioactive agent (claim 57), or a step of processing the heteropolymer particles into a product that is among those recited by claims 61-62 such as soy milk.
Pabst discloses a non-human milk baby formula comprising an enzyme, wherein the enzyme may be encapsulated (Abstract and column 3, last paragraph). The milk formula may be made from soy proteins such that it is a “soy milk” (column 2, last full paragraph). Pabst discloses that ingredients of the composition are sterilized (column 6, last full paragraph).
As to claim 45, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the method of Subramaniam by selecting an enzyme as the bioactive agent, because Subramaniam does not limit the identity of the bioactive and Pabst expressly teaches that enzymes are a suitable bioactive agent for delivery via encapsulation, such that the skilled artisan reasonably would have expected that the Subramaniam capsules could be used to encapsulate an enzyme for delivery.
Regarding claims 61-62, it further would have been prima facie obvious to process the heteropolymer particles obtained by the method of Subramaniam and Oudgenoeg as combined supra by incorporating them into a soy milk, because Pabst expressly teaches that enzymes can be useful ingredients in soy milk products and that it can be advantageous to encapsulate them in such products. Such a modification is merely the combining of known elements according to known methods to achieve predictable results, which is prima facie obvious. MPEP 2143.
Regarding claim 57, it further would have been prima facie obvious to sterilize one or more of the ingredients of the microcapsule prior to encapsulation in order to prevent microbial contamination of the milk product as is taught by Pabst.
Claim 59 is rejected under 35 U.S.C. 103 as unpatentable over Subramaniam et al. (US Pat. Pub. 2004/0032036; of record in IDS) in view of Oudgenoeg et al. (EP 1 169 922) as applied to claims 40-42, 48-52, 56, 60, and 63 above, and further in view of Yulai et al. (US Pat. Pub. 2010/0173002; of record).
The teachings of Subramaniam and Oudgenoeg are relied upon as discussed above, but they do not further expressly disclose providing an antioxidant in step (a) such that it is comprised in the same phase as the heteropolymer particles as recited by claim 59.
Yulai is directed to microcapsules comprising a gelatin protein shell formed using a coacervation process, wherein the shell material may be crosslinked using a plant extract or a phenolic compound, and wherein antioxidants are added to the emulsion prior to the microcapsule formation process as processing aids (paragraphs 30, 86, 89, 98-99).
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the method of Subramaniam and Oudgenoeg as combined supra by adding an antioxidant in step a) so that it is present in the same phase as the heteropolymer particles, because Yulai teaches that antioxidants are useful processing aids during the formation of microcapsules comprising a crosslinked protein shell using a coacervation process.
Response to Applicant’s Arguments
Applicant’s arguments will be addressed to the extent they may be relevant in light of the new grounds of rejection.
Applicant argues that unlike the claimed method, Subramaniam describes crosslinking to harden after coacervation while the invention crosslinks before or during coacervation, which results in microcapsules that are structurally different and show behavior in phase separation that enables high cell loading and efficiency and stable microcapsules for food applications, citing to Example 2 and Figures 2-7 for support. Applicant asserts that these properties could not have been predicted absent hindsight from the present specification.
In response, arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984).
Here, while Applicant asserts that the change in timing of the crosslinking step results in a structural difference in the microparticles, the nature of the structural difference is not specified, and no actual evidence is currently of record that supports the argument for a structural difference. The Office has reviewed Example 2 and Figures 2-7, but they do not appear to provide any comparison between encapsulated particles formed from a method wherein crosslinking occurs after as opposed to prior to or simultaneously with coacervation.
Conclusion
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/GAREN GOTFREDSON/Examiner, Art Unit 1619
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/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600