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 the Claims
Claims 2, 5-6, 11, 14-15 and 20-26 are cancelled. Claims 27-31 are new. Claims 1, 3-4, 7-10, 12-13, 16-19 and 27-31 are pending. Claims 1, 3-4, 7-8, and 18-19 are withdrawn. Claims 9-10, 12-13, 16-17, and 27-31 are under examination.
Priority
This application is a national stage entry of PCT/US2022/032640 filed on 6/8/2022, which claims priority from US provisional application 63/210,533 filed on 6/15/2021.
Objections/Rejections Withdrawn
The objection over claim 9 is withdrawn per applicant’s amendment to claim 9.
The rejection under USC 112(a) for written description is withdrawn per applicant’s amendments to claims 9 and 10.
The rejections under USC 112(b) from the previous rejection are withdrawn per applicant’s amendments and cancellations.
The rejection under USC 103 over Ansari et al (AMB Express, 2017, volume 7, pages 1-8), Reed US 20170142967, and Arribas et al (Br J Pharmacology, 2009, volume 157, pages 1024-1033) is withdrawn per applicant’s amendments.
As these rejections are withdrawn, applicant’s arguments to these rejections are moot.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 9-10, 12-13, 16, 28, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (Advanced Materials, 2017, volume 29, pages 1-7) and Yus et al (Polymers(Basel), Oct 2019, volume 11, pages 1-14).
Claim 9 is a product by process claim (MPEP 2113). A materially similar product may be made by different processes.
Kim teaches a cytoprotective FeIII–TA (Tannic acid) shell that forms on the surface of the alginate microbead, which then entraps probiotic Lactobacillus acidophilus (abstract). Kim teaches the interfacial supramolecular self-assembly and film formation of ferric ions (FeIII) and tannic acid (TA) in biphasic systems is reported, where Fe III and TA come into contact each other and self-assemble across the interface of two immiscible phases (abstract). Kim teaches a pericellular Fe III–TA shell that forms on individual Saccharomyces cerevisiae (abstract). Kim teaches different assemblies of the FeIII-TA-MOC to produce microcapsules or microbeads (figure 1 legend). Figure 2 teaches the hollow microcapsules with yeast cells inside (page 2). Kim provides the probiotic capsules have potential to be taken orally (page 4, first column).
Kim does not provide for a second layer that has a compound or composition as in claim 9 and 10, however, Kim does note the capability of using its encapsulated probiotics orally. Kim does not teach E coli.
Yus teaches “The development of advanced probiotic delivery systems, which preserve bacteria from degradation of the gastrointestinal tract and achieve a targeted release mediated by pH-independent swelling, is of great interest to improve the efficient delivery of probiotic bacteria to the target tissue. Gram-positive and Gram-negative bacteria models (Lactobacillus acidophilus (Moro) Hansen and Mocquot (ATCC®4356™) and Escherichia coli S17,respectively) (an E coli) have been successfully encapsulated for the first time in pH-independent microparticulate polymethacrylates (i.e., Eudraguard biotic) used for the targeted delivery of nutraceuticals to the colon” (abstract and section 2.1-2.2). Yus teaches “These results underline the suitability of the synthesized materials for the successful delivery of probiotic formulations to the target organ, highlighting for the first time the potential use of Eudraguard biotic as an effective enteric coating for the targeted delivery of probiotics” (abstract). Yus teaches Eudragit RS 100 (abstract). Yus teaches “The enteric microparticles remained unaltered under simulated gastric conditions and released the contained viable microbial cargo under simulated intestinal conditions.” (abstract).
One of ordinary skill in the art would further provide an enteric Eudragit layer taught in Yus for probiotic delivery systems of Kim as it would be seen as protecting the system from the stomach and allowing release in the intestine where the probiotic is desired. Kim teaches a system where probiotic is encapsulated by FeIII-tannic acid and that may be used orally, and thus, would be seen as a probiotic delivery system that would benefit from having an enteric coating for oral administration. Thus, there was a reasonable expectation of success in combining the teachings of Kim and Yus to provide for enterically coated (Eudragit coated)-FeIII-tannic acid microcapsules containing a probiotic that will protect the probiotic until delivery to the intestines. Kim further teaches E coli as a probiotic that can be used.
Claim 17 in addition to claims 10 and 16 is rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (Advanced Materials, 2017, volume 29, pages 1-7); Yus et al (Polymers(Basel), Oct 2019, volume 11, pages 1-14) and Arribas et al (Br J Pharmacology, 2009, volume 157, pages 1024-1033).
Kim and Yus teach the claims as discussed above. Yus also provides for E coli.
Kim and Yus do not teach E coli Nissle 1917 cells (a particular probiotic strain of E coli).
Arribas teaches “Escherichia coli Nissle 1917 is a probiotic strain used in the treatment of intestinal immune diseases, including ulcerative colitis” (abstract). Arribas teaches that the effects can occur with oral administration (abstract).
Thus, one of ordinary skill in the art before the time of filing would have selected E coli Nissle 1917 cells as a probiotic strain that has beneficial effects on intestinal health. There would be a reasonable expectation of using another probiotic in the probiotic formulation taught by Kim and Yus with the expectation of it exerting better health benefit since more viable probiotic cells will make it to the intestine via the probiotic cell protective effects from a composition of the teachings of Kim and Yus.
Response to Applicant’s Arguments over the Maintained Rejections
Applicant argues that there is no teaching that Eudragit could be coated effectively on an ferric ion-crosslinked tannin layer. Applicant mentions the ferric-tannic acid shells would have distinct physiochemical properties and there is no teaching of the ability to coat the surface of the FeIII-TA layered probiotic, however, applicant does not provide what those properties are and where the art would recognize this as substantially problematic with Eudragit and polymethacrylate coatings, particularly. The applicant’s claims are to a composition with a first and second layer/coating over a probiotic, where a probiotic would be a beneficial bacteria to be delivered to the gut of a subject. Kim teaches a cytoprotective FeIII–TA (Tannic acid) shell that forms on the surface of the alginate microbead, which then entraps probiotic Lactobacillus acidophilus (abstract) while the teachings of Yus provide for particles of probiotic that have polymethacrylate layers for targeted release in the intestines of a subject. Thus, there are motivations to add each layer onto a probiotic bacteria, an FeIII-TA shell over the bacteria for the protection of the bacterial cell and a polymethacrylate layer to protect the probiotic formulation from the stomach so it can be released in the intestine. Each reference also provides a teaching of oral administration. One of ordinary skill in the art would consider each of these layers/coatings as beneficial to a probiotic bacteria/microorganism to be delivered orally, and thus, would have a motivation to formulate the probiotic with both layers, one for probiotic cell protection and one for targeted release of the probiotic in the intestine. Note the claims use “comprising” as a transition phrase and would be open to other components of the prior art including other coatings/layers or ingredients.
Applicant argues that it would be unpredictable using both layers of the prior art over the probiotic would work and that a Eudragit layer could even be formed on a FeIII-TA coating. As the prior art provides reasonings for use of the FeIII-TA layer and the polymethacrylate/Eudragit layer, there is motivation by one of ordinary skill in the art to provide such a formulation by routine coating/layering of an agent. The applicant has not provided objective evidence of why this would be unexpected, evidence of how this could not be routinely accomplished and/or provide significantly better probiotic delivery or effectiveness than would be considered additive for use of both coatings with recognized beneficial functions.
Applicant argues that there is no evidence that the Eudragit or polymethacrylate layer would provide any benefits with the FeIII-TA coating of Kim, which would lead to enhancement of protective effect or other benefits. Kim recognizes protection of the bacteria and Yus provides for targeted delivery to the intestine, and thus, the prior art does provide beneficial functions. Applicant has not provided evidence of why the effect of using both layers on the probiotic would be surprising or unexpected. Applicant’s arguments cannot replace the need for evidence where evidence is needed (MPEP 2145).
Applicant argues the rejection over Kim, Yus and Arribas is overcome due to deficiencies of the rejection over Kim and Yus. As provided above, the rejection over Kim and Yus is being maintained. Thus, the rejection including Arribas is proper for teaching of claim 17.
Applicant has added new claims, claims 28 and 30 are taught by Kim and Yus, since Yus teaches polymethacrylates (these are polymers of methacrylic acid). Additionally, Yus teaches Eudragit RS 100 which is made up of ethyl acrylate, methyl methacrylate and methacrylic acid. This is an obvious variant of an intestinal release coating/layer having alkyl acrylate, methyl methacrylate and methacrylic acid. In regard to claims 27, 29 and 31, the prior art had to be reconsidered and recombined to meet this new limitation in the claims.
New Rejection – As Necessitated by New Claims (Using previously cited prior art)
Claims 27, 29 and 31 in addition to claims 10, 28 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Ansari et al (AMB Express, 2017, volume 7, pages 1-8), Reed US 20170142967, Kim et al (Advanced Materials, 2017, volume 29, pages 1-7), and Arribas et al (Br J Pharmacology, 2009, volume 157, pages 1024-1033).
Ansari teaches microencapsulation with calcium alginate-chitosan and Eudragit S100 nanoparticles for the improving viability of probiotic bacteria, Lactobacillus acidophilus and Lactobacillus rhamnosus (abstract). The first coat is noted as chitosan and the second coat as the Eudragit S100 (abstract and figure 1). Ansari provides the Eudragit S100 is a copolymer of methacrylic acid and methyl methacrylate and that it is in non-soluble in acids and water while soluble in a pH solvent or higher alkaline circumstance (page 2, first column). Ansari notes that the double coated beads increase the survival rate of the probiotic bacteria as compared to single coated with an in vitro simulated stomach acid (gastric juice) followed by simulated intestinal juice (pages 5 and 6 and table 1, legend and table). Thus, the Eudragit S100 coat of Ansari operates as applicant’s second layer in the claim.
Ansari does not teach incorporating tannin into the layer overlaying the probiotic. Ansari does not teach E coli Nissle 1917 as the probiotic (elected species). Ansari does not provide at least some of the ferric (Fe3+) ion-crosslinked tannin being in contact with the probiotic.
Kim teaches a cytoprotective FeIII–TA (Tannic acid) shell that forms on the surface of the alginate microbead, which then entraps probiotic Lactobacillus acidophilus (abstract). Kim teaches the interfacial supramolecular self-assembly and film formation of ferric ions (FeIII) and tannic acid (TA) in biphasic systems is reported, where Fe III and TA come into contact each other and self-assemble across the interface of two immiscible phases (abstract). Kim teaches a pericellular Fe III–TA shell that forms on individual Saccharomyces cerevisiae (abstract). Kim teaches different assemblies of the FeIII-TA-MOC to produce microcapsules or microbeads (figure 1 legend). Figure 2 teaches the hollow microcapsules with yeast cells inside (page 2). Kim provides the probiotic capsules have potential to be taken orally (page 4, first column).
Reed teaches a matrix of chitosan and a tannin wherein the chitosan is electrostatically bonded to the tannin to form a chitosan-tannin composite material (abstract). Reed teaches “The composite materials can be used for drug delivery, for antibacterial and/or antifungal applications, for tissue engineering applications, for wound healing applications, or they can be used as adjuvants for vaccination, including oral vaccinations” (abstract). Reed teaches “The chitosan-tannin composite material can form a nanoparticle that encapsulates the bioactive agent, for example, a drug or nutrient” (paragraph 13) and also teaches probiotics as a drug or nutrient (paragraphs 13 and 100). Reed teaches encapsulation efficiencies (paragraph 247). Reed teaches “In such embodiments, the nanoparticle can protect an encapsulated material in various environments, such as in the acidic conditions of the stomach” (paragraph 11). Reed teaches the composite material can be combined with an additive in a capsule among other forms (paragraphs 98 and 105-106). Reed notes that “The tannin-chitosan composite materials provide higher biocompatibility and superior biodegradability relative to known synthetic composites” (paragraph 81). Reed teaches tannic acid as a monomeric tannin that can be present at less than 5 Wt% (paragraph 59). Thus, the layer would comprise tannin and can comprise tannic acid.
Arribas teaches “Escherichia coli Nissle 1917 is a probiotic strain used in the treatment of intestinal immune diseases, including ulcerative colitis” (abstract). Arribas teaches that the effects can occur with oral administration (abstract).
One of ordinary skill in the art before the time of filing would have been able to provide tannins including an amount of tannic acid in a chitosan layer of Ansari in order to produce a layered probiotic as the combination of tannin with chitosan offers benefits to biocompatibility and biodegradability in teachings of Reed, which also provides for use with probiotics, while Ansari provides for the structure of probiotic layered with chitosan that is then layered with a Eudragit layer/enteric layer. Ansari motivated by Reed provides for a tannin/tannic acid material that can directly coat active agents like probiotics with Kim providing tannic acid can be crosslinked with Fe3+(ferric ion) as a way to provide a tannin coating material. Thus, one of ordinary skill in the prior art would have considered the FeIII-TA protective coating of Kim as a tannin coating on the probiotic, since tannin coatings had been used directly on an active including a probiotic in Reed. Arribas provides that E coli Nissle 1917 is a probiotic useful for treating intestinal disease by oral use, which allows one of ordinary skill in the art to incorporate it into the formulation motivated by Ansari and Reed which would include probiotic. Therefore, there is a reasonable expectation of success in combining the teachings of Reed with the teachings of Ansari to produce the claimed layered composition with a reasonable expectation of success of having tannins in the layer overlaying the probiotic active. As Reed also recognizes that there may be an amount of tannic acid monomer, tannic acid would be able to be present in such a tannin-chitosan layer.
Conclusions
No claim is 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 MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613
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