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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on 09/29/2025 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a CIP of 16/862,342 (filed 04/29/2020, now abandoned), which is a CIP of PCT/US2018/058214 (filed 10/30/2018), which has a PRO 62/579,067 (filed 10/30/2017).
Claim Objections
The previous claim objections are withdrawn in light of the amendments.
Claim Rejections - 35 USC § 112
The previous claim rejections under 35 U.S.C. 112(a) and 35 U.S.C. 112(b) are withdrawn in light of the amendments.
Claim Rejections - 35 USC § 102
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 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.
Claims 20-22, 51, 53-54, 63-64, and 66 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jongpaiboonkit (“An adaptable hydrogel array format for 3-dimensional cell culture and analysis”) (newly cited).
Regarding claim 20, Jongpaiboonkit discloses a bioreactor (abstract “a hydrogel array format can be used to identify environments that promote viability of HL-1 cardiomyocytes”), comprising,
a plurality of three-dimensional structures (Fig. 1 and caption), wherein each three-
dimensional structure comprises a scaffold (Fig. 1 and caption; pg. 3347, under “2.1. Preparation of synthetic PEG hydrogel arrays”, “PEG hydrogel networks”) having a plurality of units arranged in a lattice (Fig. 1 and caption; pg. 3347, under “2.1. Preparation of synthetic PEG hydrogel arrays”, “the resulting PEG hydrogel networks contained an array of 16 spots”), the units being defined by walls of the scaffold (Fig. 1 and caption); and
polymer-immobilized whole cells (pg. 3348, under “2.4.2. Cell seeding within PEG hydrogel arrays”, “The cell/polymer solution (1 μl) was pipetted in the wells of the hydrogel array”) present in at least some of the units (Fig. 1 and caption; pg. 3347, under “2.1. Preparation of synthetic PEG hydrogel arrays”, “the resulting PEG hydrogel networks contained an array of 16 spots”).
Regarding the limitation “printed three-dimensional structures”, is a product-by-process limitation. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
Regarding claim 21, Jongpaiboonkit discloses wherein the scaffold (Fig. 1 and caption; pg. 3347, under “2.1. Preparation of synthetic PEG hydrogel arrays”, “PEG hydrogel networks”) comprises at least one sidewall (Fig. 1 and caption, sidewall created from Teflon mold) having a thickness defined by a length of one unit (Fig. 1 and caption, sidewall created from Teflon mold has a thickness of the sidewall of the well of the hydrogel array).
Regarding claim 22, Jongpaiboonkit discloses wherein each unit has a dimension measured between the opposite walls of the unit, wherein the dimension has a length of at least 250 microns (pg. 3347, under “2.1. Preparation of synthetic PEG hydrogel arrays”, “a Teflon mold containing 16 cylindrical posts (1 mm diameter, 1.25 mm depth)”, it is inherent that 1 mm is 1000 μm or microns).
Regarding claim 51, Jongpaiboonkit discloses wherein the plurality of units have at least one substantially uniform dimension (pg. 3347, under “2.1. Preparation of synthetic PEG hydrogel arrays”, “a Teflon mold containing 16 cylindrical posts (1 mm diameter, 1.25 mm depth)”, the uniform dimensions being the same 1 mm diameter and 1.25 mm depth).
Regarding claim 53, Jongpaiboonkit discloses wherein the bioreactor is configured to operate at a temperature that correlates to a viable temperature of the polymer-immobilized whole cells (pg. 3347, under “2.2. Preparation of natural hydrogel arrays”, Fig. 1 and caption, and Fig. 3 caption; “37 °C”).
Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of Jongpaiboonkit would be fully capable of operating in this manner given the structure of the hydrogel arrays.
Regarding claim 54, Jongpaiboonkit discloses wherein the bioreactor is configured to operate at a temperature in a range of greater than 20 degrees Celsius to less than about 45 degrees Celsius (pg. 3347, under “2.2. Preparation of natural hydrogel arrays”, Fig. 1 and caption, and Fig. 3 caption; “37 °C”).
Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of Jongpaiboonkit would be fully capable of operating in this manner given the structure of the hydrogel arrays.
Regarding claim 63, Jongpaiboonkit discloses a bioreactor (abstract “a hydrogel array format can be used to identify environments that promote viability of HL-1 cardiomyocytes”) comprising,
a plurality of three-dimensional structures (Fig. 1 and caption), wherein each three-dimensional structure comprises a scaffold (Fig. 1 and caption; pg. 3347, under “2.1. Preparation of synthetic PEG hydrogel arrays”, “PEG hydrogel networks”) having a plurality of units arranged in a lattice (Fig. 1 and caption; pg. 3347, under “2.1. Preparation of synthetic PEG hydrogel arrays”, “the resulting PEG hydrogel networks contained an array of 16 spots”), with each unit being defined by walls of the scaffold (Fig. 1 and caption), and
wherein each unit defines a void volume (Fig. 1 “3D hydrogel array “background” formed” and caption) that for at least some of the units is infilled with a hydrogel (Fig. 1 “Filled each well with 1 μl of a hydrogel precursor solution + cells using Liquid Handing” and caption) having polymer-immobilized whole cells therein (Fig. 1 “Filled each well with 1 μl of a hydrogel precursor solution + cells using Liquid Handing” and caption).
Regarding the limitation “printed three-dimensional structures”, is a product-by-process limitation. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
Regarding claim 64, Jongpaiboonkit discloses wherein the scaffolds comprise a cured ink (Fig. 1 “UV for 3 min. (2nd crosslinking)” and caption) having the polymer-immobilized whole cells therein (pg. 3348 “The background arrays were then exposed to UV light for 5 min to crosslink the interpenetrated polymer, placed in PBS, and stored in a cell culture incubator” and “Cells were photoencapsulated in a 10 wt% polymer solution”).
Regarding claim 66, Jongpaiboonkit discloses wherein the scaffolds comprise a cured ink (Fig. 1 “UV for 3 min. (2nd crosslinking)” and caption) having the polymer-immobilized whole cells therein (pg. 3348 “The background arrays were then exposed to UV light for 5 min to crosslink the interpenetrated polymer, placed in PBS, and stored in a cell culture incubator” and “Cells were photoencapsulated in a 10 wt% polymer solution”).
Claim Rejections - 35 USC § 102 | 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 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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 50 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jongpaiboonkit (“An adaptable hydrogel array format for 3-dimensional cell culture and analysis”) (newly cited); or in the alternative, under 35 U.S.C. 103 as obvious over Jongpaiboonkit (“An adaptable hydrogel array format for 3-dimensional cell culture and analysis”) (newly cited) as applied to claim 20, in view of Mellot (US 20190241849) (previously cited).
Regarding claim 50, Jongpaiboonkit discloses wherein a geometry of at least some of the plurality of three-dimensional structures is selected from the group consisting of: a cylinder (Fig. 1 and caption; pg. 3347, left col., “a hydrogel “background” containing cylindrical spots”).
Assuming arguendo that Jongpaiboonkit does not read on the claim, Mellot discloses wherein a geometry of each printed three-dimensional structure is a cylinder (paragraph [0036]), a sheet (paragraph [0011] “a plurality of layers”), and a cubic structure (paragraph [0036]).
In the analogous art of cell culture substrates, it would have been obvious to one skilled in the art before the effective filing date to modify the three-dimensional structures of Jongpaiboonkit with the differing shapes of Mellot in order to configure the structure to have various shapes, sizes, and dimensions for additional cell culture area as needed, and to fit within various bioreactors and cell culture vessels (Mellot, paragraph [0036]).
Regarding the limitation “the plurality of printed three-dimensional structures”, is a product-by-process limitation. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 45, 47-49, and 55-58 are rejected under 35 U.S.C. 103 as being unpatentable over Jongpaiboonkit (“An adaptable hydrogel array format for 3-dimensional cell culture and analysis”) (newly cited) as applied to claim 20, in view of Silverman (US 20150232888) (previously cited).
Regarding claim 45, Jongpaiboonkit discloses polymer-immobilized whole cells (pg. 3348, under “2.4.1. Cell culture”, “hMSCs … HUVECs … HL-1 cells”).
Jongpaiboonkit does not disclose wherein the polymer-immobilized whole cells are selected from the group consisting of: yeasts, methanotrophic organisms, and methylotrophic organisms.
Silverman discloses wherein the polymer-immobilized whole cells (paragraph [0100] “calcium alginate gel bead”) are selected from the group consisting of: yeasts (paragraph [0053]), methanotrophic organisms (paragraph [0054]), and methylotrophic organisms (paragraph [0055]).
In the analogous art of genetically engineered microbes, it would have been obvious to one skilled in the art before the effective filing date to modify Jongpaiboonkit with the polymer-immobilized whole cells of Silverman in order to biologically oxidize hydrocarbons (Silverman, paragraph [0019]) so that there is a way to produce methanol and other alcohol products (Silverman, paragraph [0007]).
Regarding claim 47, Jongpaiboonkit does not disclose wherein the methanotrophic organisms include a strain that is genetically-engineered strain.
Silverman discloses wherein the methanotrophic organisms (paragraph [0054]) include a strain that is genetically-engineered strain ([0052]-[0054]).
In the analogous art of genetically engineered microbes, it would have been obvious to one skilled in the art before the effective filing date to modify modified Jongpaiboonkit with the genetically-engineered strain of methanotrophic organisms of Silverman in order to biologically oxidize hydrocarbons (Silverman, paragraph [0019]) so that there is a way to produce methanol and other alcohol products (Silverman, paragraph [0007]).
Regarding claim 48, Jongpaiboonkit does not disclose wherein the methanotrophic organisms include a strain that utilizes a gas as a substrate, wherein the substrate is configured to provide a carbon source and an energy source.
Silverman discloses wherein the methanotrophic organisms include a strain (paragraph [0054] for example strains) that utilizes a gas as a substrate, wherein the substrate is configured to provide a carbon source and an energy source (paragraphs [0008]-[0009], [0023], and [0054] “converting methane into methanol” and “methane as its primary carbon and energy source”).
In the analogous art of genetically engineered microbes, it would have been obvious to one skilled in the art before the effective filing date to modify Jongpaiboonkit with the strain of methanotrophic organism that utilizes a gas for a carbon and energy source of Silverman in order to biologically oxidize hydrocarbons (Silverman, paragraph [0019]) so that there is a way to produce methanol and other alcohol products (Silverman, paragraph [0007]).
Regarding claim 49, Jongpaiboonkit discloses wherein the polymer-immobilized whole cells are present in a concentration of 1×106 cells/ml of solution (pg. 3348, under “2.4.2. Cell seeding within PEG hydrogel arrays”, “seeding density of 1×106 cells/ml of solution”).
Jongpaiboonkit does not disclose wherein the polymer-immobilized whole cells are present in a concentration that provides an optical density in a range of approximately 1 to about 200.
Silverman discloses wherein the polymer-immobilized whole cells (paragraph [0132]) are present in a concentration that provides an optical density in a range of approximately 1 to about 200 (paragraph [0156] “OD 15”).
In the analogous art of genetically engineered microbes, it would have been obvious to one skilled in the art before the effective filing date to modify modified Jongpaiboonkit with the polymer-immobilized whole cells of Silverman at an optical density of 1 to 200, in order to biologically oxidize hydrocarbons (Silverman, paragraph [0019]) so that there is a way to produce methanol and other alcohol products (Silverman, paragraph [0007]).
Regarding claim 55, Jongpaiboonkit discloses wherein the bioreactor is configured to permit a flow of gas through the bioreactor such that the gas contacts the polymer-immobilized whole cells (pg. 3348, under “2.4.1. Cell culture”, “Cell cultures were maintained at 37 °C/5% CO2 and the media were replaced every 3–4 days”).
Jongpaiboonkit does not disclose that a product is formed as a result of an uptake of the gas by the polymer-immobilized whole cells.
Silverman discloses: wherein the bioreactor is configured to permit a flow of gas through the bioreactor (paragraphs [0050] and [0098]) such that the gas contacts the polymer-immobilized whole cells (paragraph [0132] “gas phase bioreactor is a fluidized bed reactor … a solid matrix is a … calcium alginate gel bead”) and a product is formed as a result of an uptake of the gas by the polymer-immobilized whole cells (paragraph [0126] “one light alkane or alkene from a gas source into the bioreactor … such that the microorganism or cell-free fractions oxidize the light alkane into a corresponding alcohol product or the alkene into a corresponding epoxide product”).
In the analogous art of genetically engineered microbes, it would have been obvious to one skilled in the art before the effective filing date to modify Jongpaiboonkit with the polymer-immobilized whole cells of Silverman in order to biologically oxidize hydrocarbons (Silverman, paragraph [0019]) so that there is a safe, efficient, specific, environmentally clean, and cost-effective way to produce methanol and other alcohol products of higher value for fuels and chemicals (Silverman, paragraph [0007]).
Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Jongpaiboonkit would be fully capable of operating in this manner given the structure of the hydrogel arrays.
Regarding claim 56, Jongpaiboonkit discloses a cell density (pgs. 3351, under Fig. 5 and caption, “cell density”).
Jongpaiboonkit does not disclose wherein a rate of the gas uptake is controlled based at least in part on an optical density of the polymer-immobilized whole cells and an extent of immobilization of the polymer-immobilized whole cells in a geometry of each of the printed three-dimensional structures.
Regarding the phrase “wherein a rate of the gas uptake is controlled based at least in part on an optical density of the polymer-immobilized whole cells and an extent of immobilization of the polymer-immobilized whole cells in a geometry of each of the printed three-dimensional structures”, this is an inherent property of a perfusion fluid carrying a gas diffusing to cells. The cells act as a gas “sink” that uptake the gas, while the fluid acts as a gas “source” to give to the cells. It would naturally flow from this idea that a differing number of gas sinks (the cells) would influence the rate of uptake. Similarly, the location of these gas sinks within a geometry of each printed three-dimensional structure (close or far away from the gas source) would influence at least the transient rate of uptake.
Regarding the limitation “printed three-dimensional structures”, is a product-by-process limitation. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
Additionally, regarding the phrase “wherein a rate of the gas uptake is controlled based at least in part on an optical density of the polymer-immobilized whole cells and an extent of immobilization of the whole cells in a geometry of each of the printed three-dimensional structures” the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Jongpaiboonkit would be fully capable of operating in this manner given the polymer-immobilized whole cells and the three-dimensional structures.
Regarding claim 57, Jongpaiboonkit does not disclose wherein the product is selected from the group consisting of: a chemical intermediate, a fuel, and carbon dioxide.
Silverman discloses wherein the product is selected from the group consisting of: a chemical intermediate (paragraph [0019] “wherein the alkane(s) is subsequently converted to its corresponding alcohol(s) and/or the alkene(s) is subsequently converted to its corresponding epoxide(s)”) and a fuel (paragraph [0008], “methanol”).
In the analogous art of genetically engineered microbes, it would have been obvious to one skilled in the art before the effective filing date to modify Jongpaiboonkit with the microbes of Silverman to obtain the products as in Silverman for the production of higher value fuels and chemicals in a manner that is environmentally clean and cost-effective (Silverman, paragraph [0007]).
Regarding the limitations “a chemical intermediate, a fuel, and carbon dioxide”, the other limitations need not be rejected at this time, as they are claimed in the alternative.
Regarding claim 58, Jongpaiboonkit does not disclose wherein the gas is a mixture comprising at least two gases selected from the group consisting of: methane, air, and carbon dioxide (pg. 3348, under “2.4.1. Cell culture”, “Cell cultures were maintained at 37 °C/5% CO2 and the media were replaced every 3–4 days”; air and carbon dioxide).
Silverman discloses wherein the gas is a mixture comprising at least two gases selected from the group consisting of: methane and air (paragraph [0097]).
In the analogous art of genetically engineered microbes, it would have been obvious to one skilled in the art before the effective filing date to modify Jongpaiboonkit with the polymer-immobilized whole cells of Silverman in order to biologically oxidize hydrocarbons (Silverman, paragraph [0019]) so that there is a safe, efficient, specific, environmentally clean, and cost-effective way to produce methanol and other alcohol products of higher value for fuels and chemicals (Silverman, paragraph [0007]).
Claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Jongpaiboonkit (“An adaptable hydrogel array format for 3-dimensional cell culture and analysis”) (newly cited) in view of Silverman (US 20150232888) (previously cited) as applied to claim 45, as evidenced by Nguyen (“Metabolic role of pyrophosphate-linked phosphofructokinase pfk for C1 assimilation in Methylotuvimicrobium alcaliphilum 20Z”) (previously cited).
Regarding claim 46, Jongpaiboonkit does not disclose wherein the methanotrophic organisms include strains selected from the group of genera consisting of: Methylococcus, Methylosinus, and Methylotuvimicrobium.
Silverman discloses wherein the methanotrophic organisms include strains selected from the group of genera consisting of: Methylococcus (paragraph [0054]), Methylosinus (paragraph [0054]), and Methylotuvimicrobium (paragraph [0054] “Methylomicrobium alcaliphilum 20Z”)
In the analogous art of genetically engineered microbes, it would have been obvious to one skilled in the art before the effective filing date to modify modified Jongpaiboonkit with the polymer-immobilized whole cells of Silverman in order to biologically oxidize hydrocarbons (Silverman, paragraph [0019]) so that there is a way to produce methanol and other alcohol products (Silverman, paragraph [0007]).
Regarding the term “Methylotuvimicrobium alcaliphilum 20Z”, the term is found to be the same as Methylomicrobium alcaliphilum 20Z, as it is only a different name for the same species (evidentiary reference Nguyen, pg. 2 of 14, col 1., middle column).
Claims 52 and 65 are rejected under 35 U.S.C. 103 as being unpatentable over Jongpaiboonkit (“An adaptable hydrogel array format for 3-dimensional cell culture and analysis”) (newly cited) as applied to claim 20, in view of McKim (US 20150267158) (newly cited).
Regarding claim 52, Jongpaiboonkit discloses the bioreactor (abstract “a hydrogel array format can be used to identify environments that promote viability of HL-1 cardiomyocytes”).
Jongpaiboonkit does not disclose wherein the bioreactor includes a flow channel.
McKim discloses a flow channel (paragraphs [0023] and [0028] “channels” or “pipes”).
In the analogous art of dynamic multi organ plates, it would have been obvious to one skilled in the art before the effective filing date to modify Jongpaiboonkit with the flow channel of McKim in order to pump water, saline, blood or a simulated blood, into the system through an inlet pipe and circulate the fluid within the system (McKim, paragraph [0028]).
Regarding claim 65, Jongpaiboonkit discloses an arrangement of at least some of the plurality of units (pg. 3347, under “2.1. Preparation of synthetic PEG hydrogel arrays”, “an array of 16 spots”; Fig. 1 and caption).
Jongpaiboonkit does not disclose wherein an arrangement of at least some of the plurality of units defines a flow channel.
McKim discloses a flow channel (paragraphs [0023] and [0028] “channels” or “pipes”).
In the analogous art of dynamic multi organ plates, it would have been obvious to one skilled in the art before the effective filing date to modify Jongpaiboonkit with the flow channel of McKim in order to pump water, saline, blood or a simulated blood, into the system through an inlet pipe and circulate the fluid within the system (McKim, paragraph [0028]).
Claims 59-62 are rejected under 35 U.S.C. 103 as being unpatentable over Jongpaiboonkit (“An adaptable hydrogel array format for 3-dimensional cell culture and analysis”) (newly cited) in view of Silverman (US 20150232888) (previously cited) as applied to claim 55, further in view of Ozbolat (US 20160288414) (previously cited).
Regarding claim 59, modified Jongpaiboonkit teaches the bioreactor according to claim 55 (see rejection to claim 55).
Jongpaiboonkit does not disclose wherein the bioreactor is configured to permit addition of humidity to the flow of the gas.
Ozbolat discloses wherein the bioreactor is configured to permit addition of humidity (paragraphs [0428]-[0430]) to the flow of the gas (paragraphs [0028] and [0322]).
In the analogous art of bioprinting, it would have been obvious to one skilled in the art before the effective filing date to modify modified Jongpaiboonkit with the humidity of Ozbolat in order to retain moisture in the scaffold so that cells can continue to grow without drying the culture media from evaporation.
Regarding the phrase “wherein the bioreactor is configured to permit addition of humidity to the flow of the gas”, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Jongpaiboonkit would be fully capable of operating in this manner given the structure of the modified bioreactor.
Regarding claim 60, Jongpaiboonkit does not disclose wherein a duration of the flow of the gas is in a range of about 8 hours to about 72 hours.
Ozbolat discloses wherein a duration of the flow of the gas is in a range of about 8 hours to about 72 hours (paragraphs [0052], [0309], [0321]-[0322] “12 hours of media perfusion”).
In the analogous art of bioprinting, it would have been obvious to one skilled in the art before the effective filing date to modify modified Jongpaiboonkit with the duration of the flow of the gas of Ozbolat in order to continue to perfuse the cells with gaseous reagents for continued cell viability and manufacture of products.
Regarding the phrase “wherein a duration of the flow of the gas is in a range of about 8 hours to about 72 hours”, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Jongpaiboonkit would be fully capable of operating in this manner given the modified bioreactor.
Regarding claim 61, Jongpaiboonkit does not disclose wherein the bioreactor is configured to permit a flow of liquid through the bioreactor concurrently with the flow of the gas in order to collect the product.
Ozbolat discloses wherein the bioreactor is configured to permit a flow of liquid through the bioreactor concurrently with the flow of gas (Fig. 38a-e and paragraph [0322] “The bubble was moving along the media flow.”)
In the analogous art of bioprinting, it would have been obvious to one skilled in the art before the effective filing date to modify modified Jongpaiboonkit’s bioreactor with a flow of liquid such as that of Ozbolat in order to supply liquid and gaseous nutrients to cells simultaneously so that the cells can grow continuously.
Regarding the phrase “in order to collect the product”, this is a form of intended use. Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Ozbolat would be fully capable of operating in this manner given the components of the bioreactor. Specifically, the product concentration (in this case, insulin) was sampled with supernatant collection and tested with a Roche Cobas insulin kit (see Ozbolat, Figs. 41A-43F and paragraphs [0327]-[0329]).
Regarding the phrase “wherein the bioreactor is configured to permit a flow of liquid through the bioreactor concurrently with the flow of the gas in order to collect the product”, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Jongpaiboonkit would be fully capable of operating in this manner given the structure of the modified bioreactor.
Regarding claim 62, Jongpaiboonkit discloses wherein the liquid includes a buffer solution having nutrients for the polymer-immobilized whole cells (pg. 3348, under “2.4.1. Cell culture”, “Mesenchymal Stem Cell Growth Medium”, “endothelial cell growth medium”, “DMEM”, “Complete Claycomb Medium”).
Additional Prior Art References
The prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure.
Berry (US 20130034898) (newly cited) – This invention is a matrix scaffold for cell culture.
He (CN 104232484) (machine translation) (newly cited) – This invention is a cell co-culture model and preparation method.
Rutz (US 20150084232) (newly cited) – This invention is the poly(ethylene glycol) cross-linking of soft materials to tailor viscoelastic properties for bioprinting.
Golway (US 20170009194) (newly cited) – This invention is about vascularized in vitro perfusion devices, methods of fabricating, and applications thereof.
Response to Arguments
Applicant’s arguments with respect to the claims have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
The previous primary reference Lee has been replaced with new primary reference Jongpaiboonkit.
Regarding the dependent claims, these claims are rejected as the independent claim is still rejected and no further arguments were made regarding the dependent claims.
Conclusion
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/N.G.E./Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799