DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Amendments
2. The amendment filed Feb. 6, 2026 have been entered. Claims 1, 7,15, and 19-20 have been amended. Claims 5-6, 8-9, 16-17 and 21 were cancelled. Claims 22-25 were newly added. Claims 1-4, 7, 10-15, 18-20 and 22-25 are under consideration in this Office Action.
Withdrawal of Claim Rejections
3. The rejection of claims 19-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in view of applicants amendments.
4. The rejection of claims 5-7 and 19-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of applicants amendments.
5. The rejection of claims 1-4, 7-8, 10-16 and 18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Popplewell et al., is withdrawn in view of applicants amendments and arguments.
6. The rejection of claims 5-6, 9 and 17 under 35 U.S.C. 103 as being unpatentable over Popplewell et al., as applied to claims 1-4, 7-8, 10-16 and 18 above, and further in view of Lehner et al., and Wang et al., is withdrawn in view of applicants amendments and arguments.
7. The rejection of claims 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Popplewell et al., in view of Naidu is withdrawn in view of applicants amendments and arguments.
New Grounds of Rejection Necessitated By Applicants Amendments
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 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.
8. Claims 1-4, 7, 10-15, 18-20 and 22-25 are rejected under 35 U.S.C. 103 as being unpatentable over Popplewell et al., (US20180110250 published April 26, 2018; priority to April 24, 2015) in view of Chung et al., (Biomater. Sci., 2013,1, 763-773)
and Lehner et al., (ACS Synthetic Biology. Vol. 6, Issue 7. Feb. 22, 2017).
The claims are drawn to a method of making a probiotic delivery system, comprising the steps of: combining at least one probiotic with bioink to produce a probiotic-seeded bioink wherein the bioink comprises about 2% w/v alginate and about 10% w/v gelatin and wherein the bioink comprises between about 106 and 109 of the at least one probiotic per mg bioink; and printing a three-dimensional structure using the probiotic-seeded bioink and a probiotic delivery system comprising a bioink and at least one probiotic.
Popplewell et al., describe delivery systems and methods of preparing a delivery system are described. Each method uses a first and second printing materials [abstract]. Popplewell et al., teach delivery systems can be conveniently prepared using 3D printers with suitable printing materials. The method of preparing a delivery system. The method includes the steps of: (a) providing a first and second printing materials; (b) depositing the first printing material, the second printing material, or both to form a first thin layer; (c) repeating the depositing step a predetermined number of times so that a new thin layer is formed on top of a previously formed thin layer and a solid or semisolid layer-by-layer construction is thus prepared; and curing the construction, thereby preparing a delivery system [para 7]. It is preferred that at least one of the multiple layers is different from the remaining layers in terms of thickness, porosity, polymeric material, active material, active material load, and/or diffusion rate [para 19]. The first polymer is formed by one of the following two routes: (i) extrusion of a molten polymer via a heated printer head at an elevated temperature, or (ii) polymerization of a polymer precursor and a curing/crosslinking agent followed by curing at a predetermined temperature [para 41]. The curing/crosslinking agent, also used directly or in a solvent, is added to the thin film of the polymer precursor to partially or completely polymerize the precursor so that a layer is formed. Optionally, an active material is added anytime in this step, e.g., as a mixture with the polymer precursor or with the curing/crosslinking agent, or being added separately through a printer head to a predetermined area of the thin film. After polymerization/curing, the active material is enclosed within the newly formed polymer [para 43] Thus teaching claim 12.
The probiotics, namely live microorganisms which, when administered in effective amounts, confer a beneficial physiological effect on the host [para 106]. Thus teaching claims 19-20. The delivery system of the present invention are well-suited for use, without limitation, in the following products such as oral care products like tooth paste care, health care devices such as condoms, and feminine hygiene products such as tampons [para 132, sections (d-f)]. Thus teaching oral and vaginal delivery for claims 22-25.
The delivery system can also include the following active materials, Probiotics, are namely live microorganisms which, when administered in effective amounts, confer a beneficial physiological effect on the host. Examples include L. bulgaricus, S. thermophiles, B. bifidum, L. lactis spp. Lactis, B. infantis, B. longum, L. paracasei, L. acidophilus, B. lactis, L. casei, B. adolescentis, B. breve, L. rhamnosus, and other Lactobacillus and Bifidobacterium genera [para 82 & 106]. Thus teaching claims 2-4 and 18. Popplewell et al., teach polymeric materials for 3D printing. Additional suitable polymers are gelatin [para 55]. Food grade printing materials are also contemplated. Thus teaching claims 1 and 15. Particular examples of suitable materials include sodium alginate, and proteins such as gelatin, and derivatives and mixtures thereof [para 60]. Bio-polymers that are derived from alginate, gelatin, hydrogel and starch can also be used as the encapsulating materials. Additionally, microcapsules can be made via the simple or complex coacervation of gelatin [para 79]. Thus teaching claims 7-8 and 16.
Popplewell et al., teach any 3D printer is suitable for preparing the delivery system of this invention. Examples are stereolithography systems, inkjet printing systems, selective laser sintering systems, fused deposition modeling systems, and laminate object manufacturing systems. Specialty 3D printers are designed for printing edibles from sugar, chocolate, candy, starch, and other food ingredients [para 47]. Thus teaching claim 10. As an illustration, the first outer layer, the second outer layer, the center layer, or the one or more additional layer contains a polymer that is breakable upon friction, contacting with water, changing of pH values, exposing to light (e.g., UV and visible)[para 20]. The printer heads may also include, for example, a UV light producing mechanism for curing polymers [para 38]. Thus teaching claim 13. In a stereolithography system, a thin layer of light-curable liquid resin is applied to a movable base. A light beam (e.g., UV) from a laser source is directed to a 2D cross section onto the base to polymerize the layer of resin. After solidification, to the solid layer is added another layer of liquid resin ready for curing by the UV beam [para 48]. Thus teaching claim 13. The delivery system has a multiple-layered cylindrical body including a cylindrical shell, a cylindrical core, and optionally one or more additional layers between the shell and core. The core can be hollow, which can further be filled with an active material. Still in other embodiments, the delivery system has a spherical body including a core and a spherical outer layer coating the core[ para 21-22]. Thus teaching the instant claim. However Popplewell et al., do not teach wherein between about 106 and109 cfu per mg polymer of the at least one probiotic is combined with the bioink or the bioink comprises about 2% w/v alginate and about 10% gelatin.
Chung et al., teach Bio-ink properties and printability for extrusion printing living cells. Chung et al., teach the approach to create complex three dimensional constructs containing biological cells is by a process referred to as ‘biofabrication’ or ‘bioprinting’, using an appropriately formulated bio-ink. Several biofabrication methods have been used to create 3D scaffolds as an extrusion based method that can continuously dispense materials (i.e., ‘ink’) and biological cells from a movable dispensing head or onto a moving stage to form patterns predesigned through computer-aided design (CAD) tools.4 This method has less geometrical limits than most of the conventional methods and can deposit material and cells within tens of minutes [Introduction].
Alginates (Alg) are naturally occurring polysaccharides and due to the structural similarity of alginate to ECM, these gels are used in cell delivery vehicles, and drug delivery beads [Introduction]. Alginate-gelatin (Alg-Gel) blends have been reported as potential drug delivery carriers, enzyme immobilisation beads, and sponges for tissue matrices. Here, we elaborate this approach with particular attention paid to the ink properties required for effective printing with respect to both the delivery and integrity of structure formed. Alginate was selected as the major component of the ink formulations used in this work due to its potential in biomedical applications, and its versatility in generating a range of possible inks by ionically crosslinking it or blending with another component. The techniques examined here provide the criteria and tools by which the printability of a hydrogel-based ink can be evaluated. In addition, the mechanical properties and cell compatibility of the optimum ink formation will be investigated [page 760, col. 1].
To prepare the ink solution, three different concentrations of sodium alginate solution (1, 2 and 4% w/v) were prepared in phosphate buffered saline (PBS, pH 7.4) and blended with 10% w/v gelatin solution. Ink solutions comprising alginate at 2% blended with 10% gelatin were labelled as 2% Alg-Gel [Ink preparation]. Thus teaching the instantly claims percentages of alginate and gelatin. A 2% Alg-Gel ink solution was prepared as described previously (Section 2.2) under sterile conditions [Cell Compatibility]. Printing of Alg-Gel ink solutions should be conducted at low temperatures to ensure the solutions exhibit gel-like behaviors. The 2% Alg-Gel (Fig. 2B) also showed a dominant G′ over G′′ across all frequencies [page 766]. The storage modulus of 2% Alg-Gel (Fig. 2B) was an order of magnitude higher than that of 4% Alg + Ca2+ (Fig. 1A), which could indicate a viscoelastic behaviour more suitable for extrusion printing [Printability].The compression modules showed 2% Alg and 10% Gel for a period of 15 days [page 770]. 2% Alg-Gel ink solutions showed better resolution with respect to pore diameter and filament width [Printability]. The percentage of mass loss was faster than Alg samples with 1% and 4% Alg-Gel showing a loss of around 57% and 36% respectively [Discussion].. Therefore Chung et al., teach utilizing the gelling characteristics of gelatin at low temperatures, the viscosity and storage modulus of alginate-based inks can be increased without addition of Ca2+, thereby making these gels more bio-friendly to cells. Frequency sweep measurements indicated that Alg-Gel ink solutions exhibit gel-like characteristics at low temperatures and can be consistently extruded from a nozzle. This suggested that gelation took place homogeneously and more uniformly, allowing more controllable ink deposition. A suitable ‘bio-ink’ has to fulfill various rheological, mechanical and biological requirements during and after printing. The printability, mechanical properties and cell viability characteristics of alginate-based hydrogel scaffolds were explored using various analytical techniques. By adding gelatin, the printability was enhanced considerably as shown by well-defined structures and pore diameter. The consistency of each formulation during the extrusion printing process was measured by monitoring the force fluctuations. It was shown that Alg-Gel had lesser variations than Alg + Ca2+ ink solutions [Conclusion].
Lehner et al., teach a straightforward approach for 3D bacterial printing. Lehner et al., teach 3-dimensional printing of bacterial cultures for materials production and patterning. This methodology combines the capability of bacteria to form new materials with the reproducibility and tailored approach of 3D printing systems. For this purpose, a commercial 3D printer was modified for bacterial systems, and new alginate-based bioink chemistry was developed. Printing temperature, printhead speed, and bioink extrusion rate were all adapted and customized to maximize bacterial health and spatial resolution of printed structures. Our combination of 3D printing technology with biological systems enables a sustainable approach for the production of numerous new materials [abstract]. A wide variety of 3D printing approaches have been developed for additive manufacturing of nonbiological materials, including stereolithography, selective laser sintering, electron beam melting (EBM), Laser Engineered Net Shaping, and PolyJet [Introduction]. In order to optimize the bioink composition, the alginate concentration were systematically varied (from 0.5% w/v to 6% w/v alginate; and tested in the printing system. Bacteria can thus remain viable within the alginate gel of our bioink for at least 2 days following gel formation, providing sufficient time for microbial-mediated materials production or patterning to occur [Survival and Metabolic Activity of Printed Bacteria]. Figure 5 shows CFU at 107 cells. Colony forming units (CFU) were determined. Therefore, Lehner et al., teach the about 106 and109 cfu per mg polymer of the at least one probiotic is combined with the bioink or the bioink comprises about 2% w/v alginate and gelatin.
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Chung et al., and Lehner et al., about 2% alginate and about 10% gelatin polymer/bioink ingredients and probiotic amounts to Popplewell et al., method for making and delivering a probiotic delivery system in order to provide viable bacteria in the printed gel resulting in an overall increase in viability of the probiotic bacteria. One of ordinary skill in the art would have a reasonable expectation of success by incorporating the teachings of Chung et al., Lehner et al and Popplewell et al., to produce high cell viability. Furthermore, Chung et al., and Lehner et al., taught the printability, mechanical properties and cell viability characteristics of alginate-gelatin based printable scaffolds known to include live bacterial cells.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of manufacturing when all the steps and components are well known and there is no change in the respective function of the bioink or probiotic; thus the combination would have yielded a reasonable expectation or success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
9. Applicant’s arguments, filed Feb. 6, 2026, with respect to the rejection(s) of claims 1-4, 7-8, 10-16 and 18-20 over Popplewell et al.., Lehner et al., Wang et al., and/or Naidu et al., are withdrawn in view of applicants amendments and arguments.
Applicants arguments and amendments have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new grounds of rejection is made in view of Chung et al., because Chung et al., teach the delivery system comprise about 2% w/v alginate and about 10% w/v gelatin.
While Popplewell taught the inclusion of alginate and gelatin at unspecified amounts, and Lehner et al., recited at range of alginate at 0.5% w/v to 6% w/v alginate;
neither specifically recited about 2% alginate and about 10% gelatin. Chung et al., clearly teach bioink delivery composition comprising live cells and about 2% alginate and about 10% gelatin. Moreover, Chung et al., clearly and specifically teach benefits and advantages for bioink compositions having about 2% alginate and about 10% gelatin with respect to their printability, mechanical properties and cell viability characteristics of alginate-based hydrogel scaffolds. Therefore, Chung et al., specifically and pointedly teach a delivery composition bioink to produce a live cell -seeded bioink wherein the bioink comprises about 2% w/v alginate and about 10% w/v gelatin and wherein the bioink prints a three-dimensional structure.
Claim Objections
10. Claims 22 and 24 are objected to because of the following informalities: Both claims 22 and 24 recite “…individually orally.” However, it is suggested the language recite administered to the individual orally. Appropriate correction is required.
Pertinent Art
11. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
US7051654B22 describe Ink-jet printing of viable cells.
US8137721B2 describe Ink jetting inks for food application.
EP1902107B1 describe Methods for applying ink-jettable flavored and colored fluids on edible substrates.
WO2020030628 describe edible microextruded products with compressive and tensile Young's moduli resembling the mechanical properties of meat, said edible products comprising several layers of microextruded elements made of a viscoelastic composition, said viscoelastic composition comprising in an appropriate edible solvent, high amounts of protein and an edible pseudoplastic polymer. The invention discloses also particular processes for obtaining such edible microextruded products, in particular a 3D printing method.
US 20140248246 edible webs comprising microorganisms, such as probiotics. In particular, the present invention relates to an edible web having microorganisms, such as bacteria, probiotic bacteria, bacteriophages or viruses printed thereon, e.g. by the use of inkjet printing. In addition the invention relates to methods of producing such edible webs, to various products comprising the edible webs as well as to use of the edible webs comprising microorganisms.
Conclusion
12. No claims allowed.
13. 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.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Dan Kolker, can be reached on 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/Primary Examiner, Art Unit 1645