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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-43) in the reply filed on 7/29/26 is acknowledged. Non-elected claims 44-45 were canceled.
Specification
The disclosure is objected to because of the following informalities:
In page 44, [00195], line 6, “iswell-studiedd” should read “is well studied”.
Appropriate correction is required.
Claim Objections
Claim 37 is objected because “ethyl cellulose about…;lutein about….; and corn starch between about…” should read “the ethyl cellulose is about…; the lutein is about….; and the corn starch is between about…”
Claim 38 is objected to because of the following informalities:
In claim 38, line 1, “The method of Claims 32” should read “The method of Claim 32”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 18-19, 21-22, 23-24, 27-28, 30-43 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 18 recites the limitation "the step of freeze-drying" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 18 recites the limitation "the step of lyophilizing " in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 19 is indefinite because it recites “The method of Claim 19 further comprises” and it is unclear if the claim is intended to further limit claim 1 or claim 18.
Claim 21 recites “the biopolymer is high amylose corn starch having a concentration between about 10% w/w and about 15%w/w”. It is unclear as to what has a concentration of between about 10% w/w and about 15%w/w in the biopolymer.
Claim 22 recites the limitation "the concentration of high amylose corn starch is about 15%w/w" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 23 recites the limitation "the step of heating" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 30 recites the limitation "the hydrogel encapsulated with the bioactive compound" in lines 6-7. There is insufficient antecedent basis for this limitation in the claim.
Claim 32 recites the limitation "the core solution" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 32 recites the limitation "the polymeric material solvent solution" in lines 5-6. There is insufficient antecedent basis for this limitation in the claim.
Claim 32 recites the limitation "the bioactive compound-polymeric material solvent solution" in line 7. There is insufficient antecedent basis for this limitation in the claim.
Claim 35 recites “the amount of the bioactive compound is about 20 mg/1 g of the bioactive compound”. It is unclear how the bioactive compound mg/g is based on the mg/g of itself.
Claims 38 and 40 recite, “the extruding step further comprises the step of: coaxially extruding”. The claim is indefinite because it is unclear if this “coaxially extruding” is an additional coaxial extrusion, or if it is intending to further limit the extrusion of claim 30.
Claims 24, 28, 31, and 33-43 are rejected by virtue of their dependence on rejected claims.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-4, 8-16, 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Agarwal et al. [Extrusion 3D printing with Pectin-based ink formulations: Recent trends in tissue engineering and food manufacturing, 2021], hereinafter Agarwal, evidenced by Hamilton [Needle gauge chart].
Regarding claim 1, Agarwal teaches a method for fabricating a porous hydrogel [Agarwal, p.2, left column, last paragraph; p.8, Fig.3, A(i-ii) and B(i)], the method comprising the steps of:
preparing a bio-ink composition (pectin bioink) [Agarwal, p.2, left column, par.1, 2. Pectin-based printing inks: composition and crosslinking optimization; p.6, left column, par.2], comprising a predetermined concentration of a food-grade biopolymer (pectin or pectin-based blends, and its semi-synthetic forms, which are suitable for printing at concentrations as low as 1.5% w/v) [Agarwal, p.3, left column, par.2; p.6, left column, par.2]; and
extruding the bio-ink composition from a three-dimensional food printing system to form the porous hydrogel [Agarwal, p.4-5, Table 2, Printing method & system column].
Regarding claim 2, Agarwal teaches the method of claim 1 wherein the food-grade biopolymer comprises pectin [Agarwal, p.1, Title, Abstract].
Regarding claim 3, Agarwal teaches the method of claim 2 wherein the extruding step further comprises extruding the bio-ink composition from the three-dimensional food printing system at a printing temperature of between about 23 °C to about 95 °C (23°C, 25°C and 37°C) to form the porous hydrogel [Agarwal, p.4-5, Table 2, Printing parameters column, p.5, 4th line Ref. [51] for 23°C, 5th line Ref. [53] for 25°C, p.4, 9th line Ref. [30] for 25°C, 6th line Ref. [32] for 37°C, 7th line Ref. [33] for 37°C, and 8th line Ref. [52] for 37°C], which are printing temperatures that fall within the claimed printing temperature range of between about 23 °C to about 95 °C.
Regarding claim 4, Agarwal teaches the method of claim 3 wherein the printing temperature is between about 23 °C to about 25 °C (23°C, and 25°C) [Agarwal, p.4-5, Table 2, Printing parameters column, p.5, 4th line Ref. [51] for 23°C, 5th line Ref. [53] for 25°C, and p.4, 9th line Ref. [30] for 25°C], which are printing temperatures that fall within the claimed printing temperature range of between about 23 °C to about 25 °C].
Regarding claims 8-9, Agarwal teaches the method of claim 1 wherein the extruding step further comprises extruding the bio-ink composition from the three-dimensional food printing system at a printing speed of between about 4 mm/s to about 6 mm/s to form the porous hydrogel [Agarwal, p.4, Table 2, Printing parameters column, 2nd line Ref. [40] for 4 mm/s, 6th line Ref. [32] for 5 mm/s, and 9th line Ref. [30] for 6 mm/s].
Regarding claims 10-11, Agarwal teaches the method of claim 1 wherein the extruding step further comprises extruding the bio-ink composition from the three-dimensional food printing system at a pneumatic pressure of between about 1 psi and about 120 psi (10.7-50 psi; 3 bars or 43.5 psi) [Agarwal, p.4, Table 2, Printing parameters column], and (50-80 kPa or 7-12 psi) [Agarwal, p.5, Table 2, Printing parameters column], to form the porous hydrogel.
Regarding claim 12, Agarwal teaches the method of claim 1 wherein the extruding step further comprises extruding the bio-ink composition from the three-dimensional food printing system from a nozzle having a predetermined diameter [Agarwal, p.1, right col., par.1; p.3, left col., par.1; p.4-5, Table 2, Printing parameters column], to form the porous hydrogel.
Regarding claims 13-15, Agarwal teaches the method of claim 12 wherein the nozzle diameter is between about 0.08 mm to about 1.2 mm, the method of claim 13 wherein the diameter is between about 0.08 mm and about 0.33 mm, and between about 0.108 mm and about 0.210 mm (0.200-0.2540 mm) [Agarwal, p.4-5, Table 2, Printing parameters column], (and 27 Gauge or 0.210 mm, see attached Hamilton needle gauge chart, p.1, which discloses that 27 Gauge is equivalent to 0.210mm).
Regarding claim 16, Agarwal teaches the method of claim 13 wherein the nozzle diameter is between about 0.7 mm and about 1.2 mm (0.838 mm) [Agarwal, p.5, Table 2, Printing parameters column].
Regarding claim 20, Agarwal teaches the method of claim 1 wherein the step of preparing the bio-ink composition further comprises the step of preparing an aqueous biopolymer suspension or solution [Agarwal, p.2, Table 1, lines 2-3; p.5, Table 2, Cells column, line 4; p.2, left column, par.1, 2. Pectin-based printing inks: composition and crosslinking optimization] having the predetermined concentration of the biopolymer [Agarwal, p.3, left column, par.2; p.6, left column, par.2], where Agarwal teaches that mixtures of biopolymers (i.e., pectin-alginate [Agarwal, p.6, left column, par.2; p.7, bottom par.; p.4, Table 2, Printing ink formulation column, line 2, Ref. [40] for low methoxyl pectin (LMP) and alginate composition]) in solution ink compositions are suitable for extrusion base printing [Agarwal, p.2, left column, par.1] compared with single component (i.e., pectin only) ink compositions [Agarwal, p.2, left column, par.2].
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.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claims 1-3 above, and further in view of Schmidt et al. [US20210324336A1], hereinafter Schmidt.
Regarding claim 5, Agarwal teaches the method of claim 3 as discussed above, but is silent regarding the printing temperature being between about 55 °C to about 95 °C.
Schmidt also directed to a method for three-dimensional printing with bioink [Schmidt, Abstract] by extruding the bioink [Schmidt, 0007], teaches using a printing temperature in the range of from about 4-60 °C [Schmidt, 0093], which is a printing temperature range that overlaps with the claimed printing temperature range of between about 55 °C to about 95 °C.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use printing temperatures in the range of from about 4-60 °C as taught by Schmidt, in the method of Agarwal, because Schmidt teaches that by varying the printing temperature an ordinarily skilled artisan would achieve optimal print quality according to the particular bioink being used, since different bioinks would have different rheological properties (i.e., viscosity) at different temperatures [Schmidt, 0060, 0078, 0082, 0093].
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claim 1 above, and further in view of Shin et al. [KR20210128785A], hereinafter Shin.
Regarding claim 6, Agarwal teaches the method of claim 1 as discussed above, but is silent regarding the printing height in the extrusion step of the bio-ink being between about 0.4 mm to about 5 mm.
Shin also directed to a method for three-dimensional printing with bioink [Shin, Abstract] by extrusion of the bio-ink [Shin, 0012] teaches the printing height in the extrusion step of the bio-ink being between about 0.2 mm to about 0.8 mm [Shin, 0045], which are printing height values that overlaps with the claimed printing height of between about 0.4 mm to about 5 mm.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use printing heights in the extrusion step of the bio-ink between about 0.2 mm to about 0.8 mm as taught by Shin, in the method of Agarwal, because Shin teaches that printing parameters or conditions of the extrusion step including temperature, pressure, printing speed, and printing height may vary depending on the composition of the bioink, and that printing parameters can be adjusted to achieve the desired thickness of the printed product [Shin, 0094].
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal in view of Shin as applied to claim 6 above, and further in view of Zhou [CN108543116A].
Regarding claim 7, Agarwal in view of Shin teaches the method of claim 6 as discussed above, but are silent regarding the printing height being about 2.5 cm.
Zhou also directed to a method for three-dimensional printing [Zhou, Abstract] with bioink [Zhou, 0008] teaches the three-dimensional printing method, wherein the printing height is about 25 mm (2.5 cm) [Zhou, 0045].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use printing heights of about 2.5 cm as taught by Zhou, in the method of Agarwal, because Zhou teaches that printing heights in the range of from about 10-55 mm (1-5.5 cm) are suitable printing heights [Zhou, claim 10] for method for three-dimensional printing with bioinks [Zhou, Abstract, 0008] which would vary depending on various factors such as the printing needle diameter, the printing pressure, the printing speed [Zhou, 0020], the bioink being used (i.e., sodium alginate and gelatin composite hydrogel) [Zhou, 0021], the printing barrel temperature [Zhou, 0045], the flow rate, the printing speed, and would also depend on the particular application and final dimensions (i.e., thickness, volume) of the product being printed [Zhou, 0070, 0021].
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claims 1 and 16 above, and further in view of Beyer et al. [WO2021081672A1], hereinafter Beyer.
Regarding claim 17, Agarwal teaches the method of claim 16 comprising the nozzle with the claimed diameters discussed above, and further teaches that the extrusion-based 3D printing method may provide for the use of multi-material (different types of bio-inks printing solutions, pectin or pectin-based blends, its semi-synthetic forms, such as pectin methacrylate (PECMA), low methoxyl pectin (LMP), high methoxyl pectin (HMP), alginate and pectin norbornene may be suitable for printing with said biopolymer concentrations as low as 1.5% w/v) [Agarwal, p.2, left column, par.1; p.3, left column, par.2; p.6, left column, par.2; p.1, left column, abbreviations; p.4-5, Table 2] for printing the product using said multi-material pectin-based bio-ink composition to print a core-shell product [Agarwal, p.9, left column, par.2], as disclosed in [0018] of the instant Specification “extrusion-based 3D printing that combines two different hydrogel printing materials into distinct two-layer prints (i.e., core and shell)”, but does not explicitly teaches a shell matrix solution extruder having a diameter of about 1.2 mm; and a core solution extruder having a diameter of about 0.7 mm.
Beyer also directed to a method for three-dimensional printing [Beyer, Abstract] with bioink [Beyer, 0011] teaches the three-dimensional printing method provides for printing of core/shell products (implicitly teaching core/shell bioink solutions since the bioink is the material used for the printing) with various diameters [Beyer, 0012], wherein the shell channel (for one or more different shell printing fluid(s), i.e., bioink [Beyer, 0019, 0032-0033, 0037, 0039]), may have a diameter of between about 1.0-2.0 mm (which is a range that encompass the claimed diameter of about 1.2 mm, therefore, equivalent to a shell matrix solution extruder having a diameter of about 1.2 mm) [Beyer, 0093], and wherein the core channel (for one or more different core printing fluid(s), i.e., bioink [Beyer, 0032-0033, 0037, 0039, 0177]), may have a diameter of about 0.7 mm (equivalent to a core matrix solution extruder having a diameter of about 0.7 mm) [Beyer, 0093].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a shell matrix solution extruder having a diameter of between about 1.0-2.0 mm and a core matrix solution extruder having a diameter of about 0.7 mm as taught by Beyer, in the method of Agarwal, because Beyer teaches that this would provide 3D printed products with any suitable dimensions such as cross sectional shape, a circular, oval, square or rectangular cross sectional shape [Beyer, 0093], as well as 3D printed products with varying diameters [Beyer, 0012], as well as core-shell printed products comprised of different input materials (bio-inks) comprising different concentric shells [Beyer, 0037].
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claim 1 above, and further in view of Won et al. [KR20210112975A], hereinafter Won, evidenced by LABCONCO [Introduction to freeze-drying].
Regarding claim 18, Agarwal teaches the method of claim 1 further comprises the step of freeze-drying (“post printing, the structures were lyophilized”, equivalent to freeze-dried, see LABCONCO p.1, par.1, line 1, “freeze-drying, also known as lyophilization”) the porous hydrogel [Agarwal, p.6, left col., par.4; right col., par.2; p.7, Fig.C “post freeze-drying”; bottom par. Sample (D) (ii); p.4, Table 2, sample Extrusion (BioBot1 Allevi 3D printer), Remarks], but does not explicitly teaches freeze-drying at a temperature of about -80 °C.
Won, also directed to a method for three-dimensional printing with bioink [Won, Abstract] teaches the method further comprises the step of freeze-drying the 3D-printed product at a temperature of about -80 °C [Won, 0041].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to freeze-drying the 3D-printed product at a temperature of about -80 °C as taught by Won, in the method of Agarwal, since Agarwal already teaches freeze-drying the porous hydrogel but simply did not specify a freeze-drying temperature, and further because Won teaches that a step of freeze-drying the 3D-printed product at a temperature of about -80 °C would help control the moisture of the 3D-printed product [Won, 0040-0041].
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claim 1 above, and further in view of Cho et al. [KR102256858B1 same as US20210268150A1, provided for freeze-drying/lyophilization translations], hereinafter Cho, evidenced by LABCONCO [Introduction to freeze-drying].
Regarding claim 19, Agarwal teaches the method of claim 1 further comprises the step of freeze-drying (also equivalent to lyophilizing the porous hydrogel, see LABCONCO p.1, par.1, line 1, “freeze-drying, also known as lyophilization”) the porous hydrogel (and “post printing, the structures were lyophilized”) [Agarwal, p.6, left col., par.4; right col., par.2; p.7, Fig.C “post freeze-drying”; bottom par. Sample (D) (ii); p.4, Table 2, sample Extrusion (BioBot1 Allevi 3D printer), Remarks], but does not explicitly teaches lyophilizing at a condenser temperature of about -108 °C under a vacuum pressure of about 0.015 kPa.
Cho, also directed to a method for three-dimensional printing with bioink [Cho, p.7, par.9 of KR102256858B1; Cho, 0020 of US20210268150A1] teaches the method further comprises the step of lyophilizing (also known as freeze-drying, see LABCONCO p.1, par.1, line 1, “freeze-drying, also known as lyophilization”, and Cho, 0053, “secondary freeze-drying, secondary lyophilization”) the 3D-printed product at a temperature of less than -60 °C, and a pressure of less than 15 Pa (0.015 kPa) [Cho, p.5, par.3 of KR102256858B1; Cho, 0053 of US20210268150A1]. Therefore, because Cho teaches lyophilizing the 3D-printed product at a temperature of less than -60 °C (without limitation), and a pressure of less than 0.015 kPa, and the claimed pressure is about 0.015 kPa (which include pressures of ± 10% of the base value of 0.015 kPa as disclosed in [00241] of the instant specification), and 0.015 kPa ± 10% comprise pressure values of from 0.0135-0.0165 kPa, and 0.0135 is a pressure of less than 0.015 kPa, one of ordinary skill in the art would recognize that pressures of from 0.0135-0.014 as taught by Cho (which is a pressure range that is about 0.015 kPa or 0.015 kPa ± 10%) are suitable pressures for three-dimensional printing methods with bioink.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to lyophilize the 3D-printed product at a temperature of about -108 °C or less than -60 °C, under a vacuum pressure of about 0.015 kPa as taught by Cho, in the method of Agarwal, since Agarwal already teaches lyophilizing the porous hydrogel but simply did not specify a temperature or pressure, and further because Cho teaches that a step of lyophilizing the 3D-printed product at a temperature of less than -60 °C, under a vacuum pressure of about or less than 0.015 kPa would help reduce the moisture of the 3D-printed product [Cho, p.5, par.3 of KR102256858B1; Cho, 0053 of US20210268150A1].
Claim(s) 21-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claim 20 above, and further in view of Luo et al. [Preparation and Characterization of High Amylose Corn Starch-Microcrystalline Cellulose Aerogel with High Absorption, 2019], hereinafter Luo.
Regarding claims 21-22, Agarwal teaches the method of claim 1 wherein the step of preparing the bio-ink composition further comprises the step of preparing an aqueous biopolymer suspension or solution having the predetermined concentration of the biopolymer as discussed in claim 20 above, but does not teaches the biopolymer is high amylose corn starch having a concentration between about 10% w/w and about 15%w/w, and wherein the concentration of high amylose corn starch is about 15%w/w.
Luo, directed to methods for making hydrogels with compositions comprising aqueous biopolymer suspension or solution, wherein the biopolymer is high amylose corn starch having a concentration between about 10% w/w and about 15%w/w, and wherein the concentration of high amylose corn starch is about 15%w/w [Luo, p.2-3, section 2. Materials and Methods, sub-section 2.2 Preparation of High Amylose Corn Starch-Microcrystalline Cellulose Hydrogel].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include the aqueous biopolymer suspension or solution of high amylose corn starch having a concentration between about 10% w/w and about 15%w/w, and wherein the concentration of high amylose corn starch is about 15%w/w as taught by Luo, in the method of Agarwal, since Agarwal already teaches a step of preparing a bio-ink composition comprising the step of preparing an aqueous biopolymer suspension or solution having the predetermined concentration of the biopolymer, and does not teaches away from using high amylose corn starch. Further, would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include the aqueous biopolymer suspension or solution of high amylose corn starch having a concentration between about 10% w/w and about 15%w/w, and wherein the concentration of high amylose corn starch is about 15%w/w as taught by Luo, in the method of Agarwal, because Luo teaches that using high amylose corn starch for preparation of hydrogels would provide biopolymer products having a porous three-dimensional structure with great absorption and viscoelastic properties, low density, abundant pores, which provided the gel products not only with the highest absorption of oils, but also with better dynamic viscoelastic properties [Luo, p.1, Abstract].
Claim(s) 23-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claim 20 above, and further in view of Wroblesky et al. [US20160046832A1], hereinafter Wroblesky, Wszola et al. [EP3769796A1], hereinafter Wszola and Osidak et al. [US20200282107A1], hereinafter Osidak.
Regarding claims 23-24, Agarwal teaches the method of claim 1 wherein the step of preparing the bio-ink composition further comprises the step of preparing an aqueous biopolymer suspension or solution having the predetermined concentration of the biopolymer as discussed in claim 20 above, but does not teaches that the method of claim 20 further comprises the step of heating the biopolymer suspension, wherein the heating step further comprises heating the biopolymer suspension to about 95°C.
Wroblesky, also directed to a method for three-dimensional printing [Wroblesky, 0011; 0047] with bio-ink (bio-printing with biocompatible and/or bioresorbable polymer (biopolymer) composition) [Wroblesky, 0049; 0108] teaches the step of preparing the bio-ink composition further comprises the step of heating the biopolymer suspension to temperatures of between about 75 °C to about 100 °C (which is a range that encompass the claimed temperature of 95 °C) [Wroblesky, 0099].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to heat the biopolymer suspension to temperatures of between about 75 °C to about 100 °C as taught by Wroblesky, in the method of Agarwal, because Wroblesky teaches that a wide range of temperatures (i.e., 25-150 °C) may be used for preparing an aqueous biopolymer suspension or solution [Wroblesky, 0099], since different biopolymers would have different dissolution temperatures and one of ordinary skill in the art would select the appropriate temperature based on the biopolymer being used during the course of normal experimentation and optimization in the method of Agarwal in view of Wroblesky, as not only Wroblesky teaches the wide range of temperatures discussed above, but also teaches that any polymer may be used or substituted depending upon the needs of the artisan [Wroblesky, 0084].
Agarwal in view of Wroblesky teaches the step of heating the biopolymer suspension, wherein the heating step further comprises heating the biopolymer suspension to about 75-100 °C as discussed above, but are silent regarding the heating being performed for about 20 minutes.
Wszola, also directed to a method for three-dimensional printing with bio-ink [Wszola, Title; 0001] teaches wherein the step of preparing the bio-ink composition further comprises the step of preparing an aqueous biopolymer (i.e., gelatin, carboxymethyl cellulose (CMC), etc.) suspension or solution comprise heating the biopolymer suspension [Wszola, 0038, l.26-36] for a time period in the range of from 15-30 minutes (which is a heating time range that encompass the claimed heating time of 20 minutes) [Wszola, 0038, l.37].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to heat the biopolymer suspension for a time period in the range of from 15-30 minutes as taught by Wszola, in the method of Agarwal, because Wszola teaches that this particular time period in the range of from 15-30 minutes while heating is suitable for dissolving biopolymers into solution for preparation of bio-inks [Wszola, 0038, l.26-37].
Agarwal in view of Wroblesky and Wszola teaches the step of heating the biopolymer suspension to about 75-100 °C for about 15-30 minutes as discussed above, but are silent regarding performing high shear at about 4,260 rpm during said heating step.
Osidak, also directed to a method for three-dimensional printing with bio-ink [Osidak, Abstract; 0060] teaches wherein the step of preparing the bio-ink composition further comprises the step of preparing an aqueous biopolymer (i.e., collagen in solution) suspension or solution comprise shearing the biopolymer suspension (while heating, which is already taught by Wroblesky [Wroblesky, 0099]) at a rate of up to 10,000 rpm [Osidak, 0031] (equivalent to performing high shear at about 4260 rpm during the heating step, since shearing the biopolymer suspension to speeds of up to 10,000 rpm include the claimed shearing conditions of about 4,260 rpm).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to subject the biopolymer suspension to high shear conditions of up to 10,000 rpm as taught by Osidak, in the method of Agarwal, since Agarwal already teaches mixing one or more biopolymers into solution for making the printing bio-ink [Agarwal, p.2, left col., par.1, section 2. Pectin-based printing inks: composition and crosslinking optimization], and Agarwal in view of Wroblesky further teaches that high shear mixing is suitable for dispersing high ratios of polypeptides (which are biopolymers) [Wroblesky, 0100]. Further, would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to subject the biopolymer suspension to high shear conditions of up to 10,000 rpm as taught by Osidak, because Osidak teaches that shearing biopolymer suspensions at a rate of up to 10,000 rpm with an incremental increase shearing rate of 500-1,000 is suitable for dissolving biopolymers into solution while increasing temperature (i.e., heating taught by Wroblesky) [Osidak, 0031].
Claim(s) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claim 20 above, and further in view of Paeschke et al. [US20080085354A1], hereinafter Paeschke and Xie [US20230390456A1].
Regarding claim 25, Agarwal teaches the method of claim 1 wherein the step of preparing the bio-ink composition further comprises preparing an aqueous alginate-pectin solution [Agarwal, p.4, Table 2, Printing ink formulation column (low methoxyl pectin (LMP)/alginate); p.6, left col., par.3; p.7, bottom paragraph], but does not explicitly teaches the alginate-pectin solution having an alginate-pectin ratio of about 80:20.
Paeschke, also directed to a method for extrusion of hydrocolloid compositions [Paeschke, Abstract], wherein the hydrocolloids include alginate and pectin [Paeschke, 0006], particularly blends of alginate and pectin, where the ratio of alginate to pectin may be in the range of 8:1 to 1:8 [Paeschke, 0007], which is an alginate to pectin ratio range that encompass the claimed alginate to pectin ratio of 80:20.
Further, Xie, also directed to a method for three-dimensional printing [Xie, 0007] with fiber compositions comprising alginate and pectin, teaches fibers comprising alginate and pectin in various ratios (without limitation) depending on the desired properties of the fibers [Xie, 0032].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a ratio of alginate to pectin in the range of 8:1 to 1:8 as taught by Paeschke, in the alginate-pectin solution of Agarwal method, because Paeschke teaches that a ratio of alginate to pectin in the range of 8:1 to 1:8 [Paeschke, 0007] is suitable for making extrudable compositions comprising a hydrocolloid (i.e., alginate) with a second hydrocolloid (i.e., pectin) [Paeschke, 0013]. Further, it would have been obvious to one of ordinary skill in the art to use various alginate to pectin ratios as taught by Xie, in the alginate-pectin solution of Agarwal method, because Xie teaches that various ratios of alginate to pectin may be selected based on the desired properties of the fibers [Xie, 0032]. Moreover, regarding the alginate-pectin ratios or concentrations, MPEP 2144.05 II. A. states: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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."
Claim(s) 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal in view of Paeschke [US20080085354A1], and Xie [US20230390456A1], as applied to claim 25 above, and further in view of Scionti [US20210345643A1].
Regarding claim 26, Agarwal in view of Paeschke and Xie teaches the method of claim 25, but does not explicitly teaches the alginate-pectin solution comprises a total gum concentration of between about 1.8 wt.% and about 2.2 wt.%.
Scionti, also directed to an extrusion-based three-dimensional printing method [Scionti, Abstract] with bio-ink (microextrudable formulations) [Scionti, 0256] teaches a bio-ink composition comprised of biopolymers (in solution, edible solvent [Scionti, 0034; 0122]) including gums, wherein the total gum concentration is in the range of 0.2-40 wt% [Scionti, 0034], with one example having a total gum concentration of 2 wt% [Scionti, 0063, Fig.16].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a total gum concentration in the range of 0.2-40 wt% or 2 wt% as taught by Scionti, because Scionti teaches that the use of gums in the bio-ink composition comprised of biopolymers can be used advantageously to form hydrogels with strong pseudoplastic behavior [Scionti, 0242], particularly because Scionti also teaches the bio-ink composition comprised of biopolymers include the same biopolymers as Agarwal of alginate and pectin [Scionti, 0110-0111].
Claim(s) 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal in view of Paeschke [US20080085354A1], and Xie [US20230390456A1], as applied to claim 25 above, and further in view of Gao et al. [Coaxial nozzle-assisted 3D bioprinting with built-in microchannels for nutrient delivery, 2015], hereinafter Gao.
Regarding claim 27, Agarwal teaches the method of claim 1, comprising extruding the bio-ink composition from a three-dimensional food printing system to form the porous hydrogel as discussed above, but is silent regarding the extruding step further comprising extruding the bio-ink composition into a calcium chloride solution.
Gao, also directed to an extrusion-based three-dimensional printing method [Gao, Abstract] teaches the extruding step further comprising extruding the bio-ink composition into a calcium chloride (CaCl2) solution [Gao, p.203, Abstract; p.205, sections 2.2-2.3, Fig.1(a); p.207, Fig.3(a), section 3.1, left column, par.1], wherein the calcium chloride solution has a concentration of 2-5% w/v [Gao, p.204, right col., section 2.1, par.1].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to extrude the bio-ink composition into a calcium chloride solution as taught by Gao, in the extrusion step of Agarwal’s method, because Gao teaches that extruding the bio-ink 3Dprinting composition into a calcium chloride solution provides the formation of high-strength product structures such as 3D printed hydrogels [Gao, p.214, left col., last paragraph; Abstract], and by adjusting the concentration and flow rate of the biopolymer/bio-ink (i.e., alginate) and calcium chloride solution the crosslinking process is facilitated [Gao, Abstract, p.205, section 2.3, right col., par.1].
Claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal in view of Paeschke [US20080085354A1], Xie [US20230390456A1], and Gao as applied to claim 27 above, and further in view of Scionti [US20210345643A1].
Regarding claim 28, Agarwal in view of Gao teaches the method of claim 27 wherein the extruding step further comprising extruding the bio-ink composition into a calcium chloride solution for crosslinking [Gao, Abstract, p.205, section 2.3, right col., par.1], but does not teaches the calcium chloride solution has a concentration of about 0.1 M.
Scionti, also directed to an extrusion-based three-dimensional printing method [Scionti, Abstract] with bio-ink (microextrudable formulations) [Scionti, 0256] teaches a bio-ink composition comprised of biopolymers in solution [Scionti, 0034; 0122], wherein the extruded product is crosslinked in a 100 mM (0.1 M) CaCl2 solution [Scionti, 0260].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a 0.1 M CaCl2 solution as taught by Scionti, in the method of modified Agarwal in view of Gao, because Scionti teaches that this would aid with the crosslinking process of the extruded product [Scionti, 0260; 0142; 0150], which is an effect that already Gao express interest in [Gao, Abstract, p.205, section 2.3, right col., par.1].
Claim(s) 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claim 1 above, and further in view of Hauser et al. [US20160375177A1], hereinafter Hauser.
Regarding claim 29, Agarwal teaches the method of claim 1, wherein the method for making bioprinted structures allows for the encapsulation of compounds/substances (i.e., fibroblasts) [Agarwal, p.6, left col., par.2], but does not explicitly teaches the method further comprises the step of encapsulating a bioactive compound, a nutraceutical, a micronutrient, a probiotic, or a combination or mixture thereof in the porous hydrogel.
Hauser, also directed to an extrusion-based three-dimensional printing method [Hauser, 0398; 0421] and hydrogels [Hauser, Abstract; 0422] teaches the method further comprises the step of encapsulating a bioactive compound (bioactive molecules) [Hauser, 0103-0105], a nutraceutical, a micronutrient (vitamins), or a combination or mixture thereof in the porous hydrogel [Hauser, 0106].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further include a step of encapsulating a bioactive compound (bioactive molecules), a nutraceutical, a micronutrient (vitamins), or a combination or mixture thereof as taught by Hauser, in the method of making the porous hydrogel of Agarwal, because Hauser teaches that this would provide hydrogels comprising a wide variety of encapsulated beneficial bioactive substances [Hauser, 0103-0112], where the hydrogels are biocompatible with said substances [Hauser, 0432], and wherein the release of encapsulated biomolecules can also be modulated by porosity [Hauser, 0439] due to the hydrogel acting as a reservoir for the sustained and controlled release of the bioactive compounds/moieties [Hauser, 0511].
Claim(s) 30-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal as applied to claim 1 above, and further in view of Beyer et al. [WO2021081672A1], hereinafter Beyer, and Hauser et al. [US20160375177A1], hereinafter Hauser.
Regarding claim 30, see claims 1, 12-17, and 29 rejections above where Agarwal teaches the method of Claim 1, and Agarwal in view of Beyer and Hauser teaches wherein the method comprises the steps of:
preparing a bio-ink solution [Agarwal, p.2, left column, par.1, 2. Pectin-based printing inks: composition and crosslinking optimization; p.6, left column, par.2]; wherein the bio-ink solution may be a core bio-ink solution (core bioink solutions implicitly taught by Beyer, since the core bioink is the material used for the printing the core-comprising three-dimensional printed products) [Beyer, Abstract; 0011-0013]; said core bio-ink solution comprising at least a bioactive compound [Hauser, 0103-0105];
preparing a bio-ink solution [Agarwal, p.2, left column, par.1, 2. Pectin-based printing inks: composition and crosslinking optimization; p.6, left column, par.2]; wherein the bio-ink solution may be a shell matrix bio-ink solution (shell matrix bioink solutions implicitly taught by Beyer, since the shell matrix bioink is the material used for the printing the shell-comprising three-dimensional printed products) [Beyer, Abstract; 0011-0012]; said shell matrix bio-ink solution comprising a food-grade biopolymer [Agarwal, p.3, left column, par.2; p.6, left column, par.2] and shell material comprise alginate (biopolymer) [Beyer, 00181]; and
and extruding [Agarwal, p.4-5, Table 2, Printing method & system column] the core bio-ink solution and the shell matrix bio-ink solution [Beyer, Abstract; 0011-0013] from a coaxial extrusion [Agarwal, p.5, Table 2, 3rd line example, Remarks column; and Beyer, 00165] nozzle of the three-dimensional food printing system [Agarwal, p.1, right col., par.1; p.3, left col., par.1; p.4-5, Table 2, Printing parameters column] to form the hydrogel [Agarwal, p.2, left col., par.5] encapsulated with the bioactive compound [Hauser, Abstract; 0422; 0103-0106].
Note: in regard to claim 30, the combination of Agarwal in view of Beyer and Hauser teaches all the limitations being claimed. See claims 1, 12-17, and 29 discussions above for the respective limitations and motivation of an ordinarily skilled artisan to modify the method of Agarwal with the teachings of Beyer and Hauser.
Regarding claim 31, see claims 29-30 rejections above.
Claim(s) 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal, Beyer [WO2021081672A1], and Hauser [US20160375177A1] as applied to claim 30 above, and further in view of Utama et al. [US20210299330A1], hereinafter Utama, and Cha et al. [KR102100506B1], hereinafter Cha.
Regarding claim 32, Agarwal in view of Beyer and Hauser teaches the method of claim 30, wherein the step of preparing the core solution further comprises the steps of:
preparing a solvent solution comprising a predetermined concentration of a core polymeric material (core liquid/solution composed of 3% polyvinyl alcohol) [Beyer, 00190];
adding an amount of a bioactive compound to the polymeric material solvent solution (i.e., adding bioactive molecules and polymer(s) [Hauser, 0117-0119; 0103-0105] to form the bioactive compound-polymeric material solvent solution (referred to by Hauser as the peptide and/or peptidomimetic and/or peptoid composition dissolved in solution [Hauser, 0094; 0099; 0167]); and
stirring the bioactive compound-polymeric material solvent solution [Hauser, 0378], (equivalent to stirring the peptide and/or peptidomimetic and/or peptoid solution as referred to by Hauser and explained above, and since the peptidomimetic and/or peptoid are used interchangeably [Hauser, 0021]), for about 15 minutes [Hauser, 0378], to form the core [Beyer, 00190] bio-ink (referred to by Hauser as biomaterial building blocks) [Hauser, 0007; 0024; 0028], (which is the bio-ink material used to make the printed hydrogel [Hauser, 0068; 0088; 0094; 0103-0105; 0115]) solution.
Modified Agarwal teaches the method and concepts discussed above to form the core bio-ink solution, where an amount of a bioactive compound is added to the polymeric material solvent solution (i.e., adding bioactive molecules and polymer(s) [Hauser, 0117-0119; 0103-0105], (therefore, because Hauser teaches adding bioactive molecules, any amount is a predetermined amount under the broadest reasonable interpretation).
However, if it could be construed that modified Agarwal in view of Hauser does not explicitly teaches the amount of the bioactive compound is specifically a predetermined amount.
Utama, directed to methods of making bio-inks for 3D printing hydrogels from a cross-linked polymer [Utama, Title; Abstract; 0002] teaches the polymer bio-ink solution may be added a predetermined amount (0.1 mM to 10 mM) of bioactive compound (bioactive molecules) [Utama, 0091].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add a predetermined amount of bioactive compound as taught by Utama, in the method of making the core bio-ink solution of modified Agarwal in view of Beyer and Hauser, because Hauser already teaches adding an amount of bioactive compound [Hauser, 0117-0119; 0103-0105] to the polymeric material solvent solution of Beyer [Beyer, 00190] as explained above, but simply did not explicitly mention specifically the amount was a predetermined amount. Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add a predetermined amount of bioactive compound as taught by Utama, because Utama teaches that addition of predetermined amounts (0.1 mM to 10 mM) of bioactive compounds (bioactive molecules) [Utama, 0091; 0102] may provide the advantage of modifying the 3D printed hydrogel to introduce certain biological characteristics [Utama, 0127].
Modified Agarwal teaches the method and concepts discussed above to form the core bio-ink solution, but does not explicitly teaches the resting for about 30 minutes at about 4 °C.
Cha, also directed to methods of making bio-inks for 3D printing hydrogels from a cross-linked polymer (i.e., chitosan, a biopolymer) [Cha, Abstract] teaches the polymeric material solution (i.e., chitosan, gelatin solution) after being stirred (the stirring already taught by Hauser as discussed above, [Hauser, 0378]) may be stored (resting equivalent) for 30 minutes at 4 °C [Cha, 0048].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a step of resting the polymeric material solution for about 30 minutes at about 4 °C as taught by Cha, in the method of making the core bio-ink solution of modified Agarwal in view of Beyer, Hauser and Utama, because modified Agarwal already teaches forming and stirring the bioactive compound-polymeric material solvent solution [Hauser, 0378] as discussed above. Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a step of resting the polymeric material solution for about 30 minutes at about 4 °C as taught by Cha, because Cha teaches that this step performed before the further processing steps helps to confirm/ensure that a gel is formed [Cha, 0048].
Claim(s) 33-34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal, Beyer [WO2021081672A1], Hauser [US20160375177A1], Utama [US20210299330A1], and Cha [KR102100506B1] as applied to claim 32 above, and further in view of Kang et al. [US20190216988A1], hereinafter Kang, and Won et al. [KR20210112975A], hereinafter Won.
Regarding claims 33-34, modified Agarwal teaches the core bio-ink solution of claim 32, but does not explicitly teaches the concentration of the polymeric material is between about 6% to about 10% w/v required by claim 33, or the concentration of the polymeric material is about 10% w/v required by claim 34.
Kang, also directed to a method for three-dimensional printing [Kang, Title] with bio-ink [Kang, Abstract] teaches a core polymeric material solution [Kang, 0012; 0095; 0103] may have a polymeric material concentration of between about 6% to about 10%, and about 10% [Kang, 0233; 0212; 0229; 0240-0243; 0255-0261], wherein said concentration may be expressed in (w/v) [Kang, p.81, Table 5].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a polymeric material concentration of between about 6% to about 10%, and about 10% as taught by Kang, in the method of making the core bio-ink solution of modified Agarwal, because Kang teaches that a wide selection of different polymer types may be used (i.e., collagen, fibrin, chitosan, alginate, oxidized alginate, starch, hyaluronic acid, laminin, agarose, gelatin, glucan, and combinations thereof [Kang, 0018]) as core polymeric material in the polymeric core solution, and one of ordinary skill in the art would recognize that different polymeric materials would have different effects and properties when using the same and/or different concentrations, which would require the use of different concentration ranges for each individual polymer type as taught by Kang [Kang, 0233; 0212; 0229; 0240-0243; 0255-0261].
If it can be construed that Kang was not clear regarding the polymeric material concentration being expressed in (w/v) in the paragraphs of Kang’s disclosure cited above ([Kang, 0233; 0212; 0229; 0240-0243; 0255-0261]);
Won, also directed to a method for three-dimensional printing with bioink [Won, Abstract] teaches a polymeric material solution may have a polymeric material concentration of between about 1-50% w/v [Won, claim 8; 0078; 0114; 0121], between about 1-10% w/v [Won, 0065; 0122], or between about 1-12% w/v [Won, 0082; 0120], (which are ranges that encompass the claimed polymeric material concentration of between about 6% to about 10%, and about 10%).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a polymeric material concentration of between about 1-50% w/v, between about 1-10% w/v, or between about 1-12% w/v as taught by Won, in the method of making the core bio-ink solution of modified Agarwal, because Won teaches that a wide selection of different polymer types may be used alone or combined (i.e., one or more biocompatible polymers and micronized polymers [Won, 0001]) including synthetic and biopolymers [Won, 0008-0009] as polymeric material in the polymeric solution, and wherein said polymers (micronized polymers) can be used to improve biocompatibility, cell adhesion, and the physical properties of bioinks [Won, 0029], where the desired physical properties can be satisfied when the above ranges taught by Won (between about 1-50% w/v [Won, claim 8; 0078; 0114; 0121], between about 1-10% w/v [Won, 0065; 0122], or between about 1-12% w/v [Won, 0082; 0120]) are used [Won, 0078; 0082].
Claim(s) 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal, Beyer [WO2021081672A1], Hauser [US20160375177A1], Utama [US20210299330A1], and Cha [KR102100506B1] as applied to claim 32 above, and further in view of Laronda et al. [US20170369851A1], hereinafter Laronda.
Regarding claim 35, modified Agarwal teaches adding a predetermined amount of the bioactive compound to the polymeric material solvent solution to form the core bio-ink solution as discussed above in claim 32, but does not explicitly teaches the amount of the bioactive compound is about 20 mg/1 g of the bioactive compound.
Laronda, also directed to a method for three-dimensional printing with bioink compositions [Laronda, 0043; 0045] for making three-dimensional porous hydrogels (scaffolds) [Laronda, 0060] by extrusion of the bioink through a nozzle [Laronda, 0006-0007], teaches the ink compositions used to print the three-dimensional porous product may comprise bioactive compounds (bioactive additives), wherein the amount of the bioactive compound is no greater than about 5% wt (or up to 50 mg/1 g) [Laronda, 0053], which is a range that encompass the claimed range of about 20 mg/1 g (2% wt) of the bioactive compound.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used bioactive compound in amounts of up to about 5% wt as taught by Laronda, in the bioactive compound-polymeric material solvent solution of Agarwal’s method, because modified Agarwal already teaches adding a predetermined amount of the bioactive compound to the polymeric material solvent solution to form the core bio-ink solution but simply did not mention a specific amount or concentration limit. Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used bioactive compound in amounts of up to about 5% wt as taught by Laronda, because Laronda teaches that a variety of different bioactive compounds may be used [Laronda, 0061], and one of ordinary skill in the art would recognize that different bioactive compounds would require to be present in the polymeric material solvent solution at different concentrations due to various factors such as the type of bioactive compound, the purity, and/or the chemical/physical properties of each particular bioactive compound, the desired effect to provide in the final printed three-dimensional porous product and/or the biocompatibility of said bioactive compound with the polymers and other additional raw materials used in the final bioink composition [Laronda, 0053; 0061].
Claim(s) 36-37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal, Beyer [WO2021081672A1], Hauser [US20160375177A1], Utama [US20210299330A1], Cha [KR102100506B1], and Laronda et al. [US20170369851A1] as applied to claim 35 above, and further in view of Meng et al. [CN113383947A], hereinafter Meng, Kang et al. [US20190216988A1], hereinafter Kang, Zeira [WO2021234448A1], and Ahn [KR20210051351A].
Regarding claim 36, modified Agarwal teaches the bioactive compound in the polymeric material solvent solution used to form the core bio-ink composition may be in amounts of up to about 5% wt or 50 mg/1 g of the bioactive compound as discussed above in claim 35, but does not explicitly teaches the bio-ink composition further comprises: ethyl cellulose between about 6% to about 10% w/v.
Meng, also directed to a method for three-dimensional printing, encapsulation or embedding of bioactive compounds [Meng, 0029] and hydrogel compositions made from polymeric substances (i.e., gelatin) [Meng, 0055; 0003], teaches a method of making a polymeric material solution/composition (emulsion-gel type composition) [Meng, 0008-0013], (equivalent to a bio-ink composition, since the polymer solution is used for 3D printing [Meng, 0031]), wherein said bio-ink composition may comprise ethyl cellulose [Meng, 0014] in an amount of about 10% [Meng, 0051]. While Meng does not specifically mentions that the 10% amount is based on (w/v), one of ordinary skill in the art would recognize the use of the percentage amount of ethyl cellulose as w/w based on the total weight of the solution or w/v based on the total volume of the solution.
Moreover, Kang, also directed to a method for three-dimensional printing [Kang, Title] with bio-ink [Kang, Abstract] teaches a core polymeric material solution [Kang, 0012; 0095; 0103] may have a polymeric material concentration of between about 6% to about 10%, and about 10% [Kang, 0233; 0212; 0229; 0240-0243; 0255-0261], wherein said concentration may be expressed in (w/v) [Kang, p.81, Table 5].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used an amount of about 10% of ethyl cellulose as taught by Meng, wherein the 10% is based on w/v as taught by Kang, in the method of modified Agarwal, because Meng teaches that by using different amount concentrations of particular raw materials such as ethyl cellulose, the physical properties of the 3D printed hydrogel such as the hardness may be modified or adjusted [Meng, 0074].
Modified Agarwal teaches the bio-ink composition further comprises ethyl cellulose at an amount of about 10% w/v, but does not explicitly teaches the bio-ink composition further comprises: lutein at about 20 mg/1 g of ethyl-cellulose.
Zeira, also directed to methods of making edible inks (bio-inks) for printing [Zeira, Abstract], teaches the bio-ink may further comprise lutein (as natural colorant) [Zeira, p.12, l.8-12] at an amount of at least 1000 mg/100g (or at least 10mg/1g) [Zeira, p.42, l.19-26], which include amounts of 10mg/1g and above of lutein (i.e., 20 mg/1 g of lutein) since Zeira does not teach an upper limit. While Zeira does not explicitly teaches the amount of lutein is 20 mg/1 g specifically based on the amount of ethyl-cellulose, because Zeira does not teaches an upper limit and the lowest limit taught by Zeira is at least 20 mg/100g (or at least 0.2mg/1g) of lutein, one of ordinary skill in the art would recognize the addition of lutein in amounts of from 0.2mg/1g and above based on the desired color strength of the final product and the particular application is being used (i.e., foods and beverages which vary in color intensity).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include lutein in amounts of from 0.2mg/1g and above or in amounts of at least 10mg/1g (or above) as taught by Zeira, in the method of modified Agarwal, because Zeira does not teaches an upper limit and the amount of lutein used as natural colorant as taught by Zeira would have been used during the course of normal experimentation and optimization in the method of modified Agarwal, based on factors such as the desired color strength of the final product, the particular application is being used, and/or the various ratios an amounts of the other ingredients.
Modified Agarwal teaches the bio-ink composition further comprises ethyl cellulose at an amount of about 10% w/v, and lutein at about 20 mg/1 g of ethyl-cellulose, but does not explicitly teaches the bio-ink composition further comprises: corn starch between about 9% and about 12% w/w.
Ahn, also directed to methods of making edible inks (bio-inks made from polymeric materials (polysaccharides such as sodium alginate, agar, konjac, tapioca, starch, corn starch, iota carrageenan, and pectin [Ahn, claim 2; 0011]), salt, fish meat surimi and pigments) and 3D printing [Ahn, Abstract], teaches the amount of corn starch in the bio-ink composition of the invention may be 10% w/w [Ahn, 0058].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include corn starch at an amount of 10% w/w as taught by Ahn, in the method of modified Agarwal, because Ahn teaches that the use of corn starch in 3D printed edible products provides an increase of hardness, gumminess, chewiness, and resilience [Ahn, 0078] and a fish paste product with appropriate hardness and resilience can be produced by the addition of corn starch [Ahn, 0093].
Regarding claim 37, for ethyl cellulose, see modified Agarwal in view of Meng and Kang in claim 36 above, teaching the bio-ink composition comprising ethyl cellulose [Meng, 0014] in an amount of about 10% [Meng, 0051], wherein said concentration may be expressed in (w/v) [Kang, p.81, Table 5].
For lutein, see modified Agarwal in view of Zeira in claim 36 above, teaching the bio-ink composition comprising lutein [Zeira, p.12, l.8-12] at an amount of at least 10mg/1g (or 10mg/1g and above) [Zeira, p.42, l.19-26].
For corn starch, see modified Agarwal in view of Ahn in claim 36 above, teaching the bio-ink composition comprising corn starch at an amount of 10% w/w [Ahn, 0058].
Claim(s) 38-39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal, Beyer [WO2021081672A1], and Hauser [US20160375177A1] as applied to claim 32 above, and further in view of Schmidt et al. [US20210324336A1], hereinafter Schmidt.
Regarding claim 38, for the extruding step further comprising the step of: coaxially extruding the core bio-ink solution, see claim 32 rejection above over Agarwal in view of Beyer, where Agarwal teaches extruding the bio-ink solution [Agarwal, p.4-5, Table 2, Printing method & system column] from a coaxial extrusion nozzle of the three-dimensional food printing system [Agarwal, p.1, right col., par.1; p.3, left col., par.1; p.4-5, Table 2, Printing parameters column], and Beyer teaches extruding the core bio-ink solution and the shell matrix bio-ink solution [Beyer, Abstract; 0011-0013].
For the extrusion temperature of about 25°C, see claim 4 above where Agarwal teaches the printing temperature (equivalent to the printing temperature) is between about 23 °C to about 25 °C (23-37°C) [Agarwal, p.5, Table 2, Printing parameters column].
For the extrusion temperature of about 55°C to about 75°C, see claim 5 above where Agarwal in view of Schmidt teaches using a printing temperature in the range of from about 4-60 °C [Schmidt, 0093], which is a printing temperature range that overlaps with the claimed printing temperature range of between about 55 °C to about 75 °C.
For the extrusion temperature of about 25°C specifically used for the extrusion of the core bio-ink solution, and the extrusion temperature of about 55°C to about 75°C specifically used for the extrusion of the shell bio-ink solution, see claim 30 above where Beyer teaches extruding the core bio-ink solution and the shell matrix bio-ink solution [Beyer, Abstract; 0011-0013], wherein the method comprise a temperature modulation component that is configured to modulate the temperature of a print head, an input fluid material, and/or a fluid (i.e., the bio-ink solution, therefore equivalent to the printing/extrusion temperature) [Beyer, 0037; 000116], and wherein the temperature modulation component is configured to adjust a temperature to a set point that ranges from about 0 to about 90° C [Beyer, 000118].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use extruding temperatures for the core and shell bio-ink solutions in the range of from about 0 to about 90° C as taught by Beyer, in the method of modified Agarwal, because Beyer teaches the method uses core and shell distinct fluids [Beyer, Abstract] and one of ordinary skill in the art would recognize that different polymer based printing fluids would require different temperatures due to their different thermal properties to achieve the appropriate viscosity and/or flow for printing.
Regarding claim 39, see claim 38 above, where Beyer teaches the method comprises extruding the core bio-ink solution and the shell matrix bio-ink solution [Beyer, Abstract; 0011-0013], and a temperature modulation component that is configured to modulate the temperature of a print head, an input fluid material, and/or a fluid (i.e., the bio-ink solution) [Beyer, 0037; 000116], said temperature modulation component being configured to adjust a temperature to a set point that ranges from about 0 to about 90° C [Beyer, 000118], which encompass the claimed extrusion temperature of between about 55 °C to about 65 °C.
Claim(s) 40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal, Beyer [WO2021081672A1], and Hauser [US20160375177A1] as applied to claim 32 above, and further in view of Ahn et al. [US20190142995A1], hereinafter Ahn.
Regarding claim 40, for the extruding step comprising the step of coaxially extruding the bio-ink solution at a pressure from the coaxial nozzle of the three-dimensional food printing system, Agarwal teaches the extruding step further comprises extruding the bio-ink composition from the three-dimensional food printing system at pressures of 50 psi, and 3 bars (43.5 psi) [Agarwal, p.4, Table 2, Printing parameters column, Examples in lines 2-3], from a coaxial extrusion [Agarwal, p.5, Table 2, 3rd line example, Remarks column; and Beyer, 00165] nozzle of the three-dimensional food printing system [Agarwal, p.1, right col., par.1; p.3, left col., par.1; p.4-5, Table 2, Printing parameters column], and Agarwal in view of Beyer teaches the extruding step comprising the step of coaxially extruding the core bio-ink solution and the shell matrix bio-ink solution [Beyer, Abstract; 0011-0013; 00142] using pressure for moving the one or more (core and shell distinct solutions/bioinks) fluids through the printing system by force [Beyer, Abstract; 00137; 00142] (equivalent to extrusion of core and shell solutions), but do not teach using a pressure between about 1 and about 3 psi specifically for the extrusion of the core bio-ink solution, and using a pressure between about 40 and 50 psi specifically for the extrusion of the shell matrix bio-ink solution.
Ahn, also directed to methods of making three-dimensional printed products [Ahn, Abstract] with two or multiple bio-inks [Ahn, Abstract, 0053-0054] teaches that suitable pressures for extruding different bio-inks are in the range of from about 0.1-700 kPa (0.01-101 psi) [Ahn, 0034; 0085], which is a pressure range that encompass the claimed pressure ranges of between about 1 and about 3 psi and between about 40 and 50 psi.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a pressure between about 1 and about 3 psi for the extrusion of the core bio-ink solution (of Agarwal in view of Beyer), and using a pressure between about 40 and 50 psi for the extrusion of the shell matrix bio-ink solution (of Agarwal in view of Beyer) taught by Ahn, in the method of modified Agarwal, because Agarwal in view of Beyer already teach using distinct fluids as core and shell bio-ink printing material [Beyer, Abstract; 00137; 00142], and Ahn also teaches that the method is suitable for using two (i.e., core and shell bioink of Beyer) or multiple bio-inks [Ahn, Abstract, 0053-0054] where a wide range of pressures may be used (0.01-101 psi) [Ahn, 0034; 0085] wherein the extruding pressure may be selected appropriately depending on the concentration of the bio-ink and the size of the extruding nozzle [Ahn, 0034].
Claim(s) 41-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal in view of Beyer [WO2021081672A1], and Hauser [US20160375177A1], as applied to claim 32 above, and further in view of Won et al. [KR20210112975A], hereinafter Won, evidenced by LABCONCO [Introduction to freeze-drying].
Regarding claims 41-42, Agarwal teaches the method of claim 32 further comprises the step of freeze-drying (“post printing, the structures were lyophilized”, equivalent to freeze-dried, see LABCONCO p.1, par.1, line 1, “freeze-drying, also known as lyophilization”) the porous hydrogel [Agarwal, p.6, left col., par.4; right col., par.2; p.7, Fig.C “post freeze-drying”; bottom par. Sample (D) (ii); p.4, Table 2, sample Extrusion (BioBot1 Allevi 3D printer), Remarks], therefore forming a cryogel since the hydrogel is freeze-dried. Further, Agarwal in view of Beyer and Hauser teaches all the limitations in claim 30 (see claim 30 discussion above, for the preparing and extruding of the core and shell bio-ink solution taught by Beyer, to form the hydrogel encapsulated with the bioactive compound taught by Hauser). Moreover, Agarwal teaches forming 3D structures in a layer-by-layer format (i.e., multiple layers) [Agarwal, p.1, left col. Introduction, par.2], forming 15-layered 3D structures [Agarwal, p.6, left col., par.2], and multilayer bioprinted constructs [Agarwal, p.7, bottom par. Introduction, par.2 and Fig.A(ii)], and Beyer teaches forming dual-layered three-dimensional (3D) structures (three-dimensional (3D) structure comprising two or more layers) [Beyer, 00162], therefore, equivalent to forming a dual-layered cryogel encapsulated with the bioactive compound. However, Agarwal does not explicitly teach freeze-drying at a temperature of about -80 °C.
Won, also directed to a method for three-dimensional printing with bioink [Won, Abstract] teaches the method further comprises the step of freeze-drying the 3D-printed product at a temperature of about -80 °C [Won, 0041].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to freeze-drying the 3D-printed product at a temperature of about -80 °C as taught by Won, in the method of Agarwal, since Agarwal already teaches freeze-drying the porous hydrogel but simply did not specify a freeze-drying temperature, and further because Won teaches that a step of freeze-drying the 3D-printed product at a temperature of about -80 °C would help control the moisture of the 3D-printed product [Won, 0040-0041].
Claim(s) 43 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal in view of Beyer [WO2021081672A1], Hauser [US20160375177A1] and Won et al. [KR20210112975A], evidenced by LABCONCO [Introduction to freeze-drying] as applied to claim 41 above, and further in view of Cho et al. [KR102256858B1 same as US20210268150A1, provided for freeze-drying/lyophilization translations], hereinafter Cho.
Regarding claim 43, modified Agarwal teaches the method of claim 41 further comprises the step of lyophilizing the hydrogel encapsulated with the bioactive compound as discussed in claim 41 above, but does not explicitly teaches lyophilizing at a condenser temperature of about -108 °C under a vacuum pressure of about 0.015 kPa.
Cho, also directed to a method for three-dimensional printing with bioink [Cho, p.7, par.9 of KR102256858B1; Cho, 0020 of US20210268150A1] teaches the method further comprises the step of lyophilizing (also known as freeze-drying, see LABCONCO p.1, par.1, line 1, “freeze-drying, also known as lyophilization”, and Cho, 0053, “secondary freeze-drying, secondary lyophilization”) the 3D-printed product at a temperature of less than -60 °C, and a pressure of less than 15 Pa (0.015 kPa) [Cho, p.5, par.3 of KR102256858B1; Cho, 0053 of US20210268150A1], which is equivalent to lyophilizing at a condenser temperature of about -108 °C since a temperature of less than -60 °C includes temperatures further below -60 including of about -108 °C, and equivalent to a vacuum pressure of about 0.015 kPa since a pressure of about 0.015 kPa as claimed include pressures of ± 10% of the base value of 0.015 kPa (as disclosed in [00241] of the instant specification), which include values of vacuum pressures in the range of from 0.0135-0.0165 kPa which is a range that overlaps with the vacuum pressure range of less than 0.015 kPa as taught by Cho.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to lyophilize the 3D-printed product at a condenser temperature of about -108 °C or less than -60 °C, under a vacuum pressure of about or less than 0.015 kPa as taught by Cho, in the method of modified Agarwal, since Agarwal already teaches lyophilizing the porous hydrogel but simply did not specify a temperature or pressure, and further because Cho teaches that a step of lyophilizing the 3D-printed product at a temperature of less than -60 °C, under a vacuum pressure of about or less than 0.015 kPa would help reduce the moisture of the 3D-printed product [Cho, p.5, par.3 of KR102256858B1; Cho, 0053 of US20210268150A1].
Conclusion
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/LUIS EUGENIO DIOU BERDECIA/Examiner, Art Unit 1792
/VIREN A THAKUR/Primary Examiner, Art Unit 1792
