DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment field May 6, 2026, has been received and entered.
Claims 11-20 are canceled.
Claims 1-10 and 21-30 are pending and examined on the merits.
Notice Re: Prior Art Available Under Both Pre-AIA and AIA
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.
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.
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 1-9 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Kajiwara (US 4,978,619. Listed on IDS filed 4/5/24) in view of Yu (Annals of the New York Academy of Sciences. 1998. 864(1): 609-615. Previously cited), as evidenced by Goodman (US 2002/0006648. Previously cited), Shum (US 2013/0274353. Previously cited), Killion (Journal of the Mechanical Behavior of Biomedical Materials. 2011. 4: 1219-1227. Previously cited), and Menner (Polymer. 2006. 47: 7628-7635. Previously cited).
Kajiwara discloses an entrapping method for the immobilization of an enzyme, wherein the enzyme immobilized can be in the form of live microorganic cells or dried microorganic cells (column 2, lines 52-59; column 3, lines 50-53; column 6, line 66 through column 7, line 2). The enzyme can be in a solution having a polymerizable monomer or a prepolymer (column 2, lines 63-66).
Examples 7 and 8 of Kajiwara meet limitations of the claimed invention. In both examples, cells of Pichia xylosa (IFO 0950) are in a mixture comprising a polyethylene glycol diacrylate (PEGDA #400, see column 10, lines 47-49) to which benzoyl peroxide is added to induce polymerization (column 12, lines 50-66; column 13, lines 35-46).
Benzoyl peroxide is a polymerization initiator (column 10, line 53). More specifically, as evidenced by Goodman, benzoyl peroxide is a photoinitiator (paragraph [0064]).
In discussing their invention, Kajiwara discloses that the immobilization of an enzyme according to their invention is initiated by mixing an enzyme or powder containing an enzyme (i.e., enzyme powder) with a solution obtained by dissolving a polymerizable monomer or prepolymer in an organic solvent thereby preparing an emulsion having the enzyme powder dispensed in the organic solvent solution of the polymerizable monomer or prepolymer (column 4, lines 17-25). Then, when discussing the emulsion, Kajiwara discloses that examples of the polymerizable monomer or prepolymer include acrylic esters and methacrylic esters (column 4, lines 62-66), and examples of the organic solvent include benzene (column 5, lines 21-24). Because of these teachings for the invention of Kajiwara, then the deaerated mixture of Examples 7 and 8 of Kajiwara comprising cells (the cells of Pichia xylosa (IFO 0950) are the “enzyme”), benzene (the organic solvent), and PEGDA (the polymerizable monomer or prepolymer that is an acrylic ester; see claim 6 of Kajiwara) (column 12, lines 57-63; column 13, lines 39-44) is directed to an emulsion; the deaerated mixture comprises all the components that are disclosed in Kajiwara for an emulsion. Therefore, the PEGDA of Kajiwara is directed to the claimed ‘at least one polymer precursor configured to form a first emulsion with the whole cells,’ since it can form an emulsion with the “enzyme” (cells of Pichia xylosa (IFO 0950)).
It is noted that the recitation in instant claim 1 of ‘at least one polymer precursor configured to form a first emulsion with the whole cells, and configured to form a second emulsion with an aqueous carrier fluid in response to immersion of droplets of the first emulsion in the aqueous carrier fluid’ does not require that the mixture comprises a first emulsion and/or a second emulsion. Instead, the limitation sets forth the intended use and functional property of the at least one polymer precursor to form a first emulsion with the whole cells, and also sets forth the intended use of the at least one polymer precursor, the intended use being forming a second emulsion with an aqueous carrier fluid by immersing droplets of the first emulsion in the aqueous carrier fluid. Emulsions of PEGDA with water are known in the art – this is evidenced by Shum (paragraph [0043]). Therefore, PEGDA of Kajiwara is suitable for the claimed intended use of forming a second emulsion with an aqueous carrier fluid in response to immersion of droplets of a first emulsion (emulsion of PEGDA with whole cells) in the aqueous carrier fluid. Additionally, PEGDA is recited in instant claims 2 and 3 as a polymer precursor, and the instant specification recognizes generating an emulsion from the combination of a polymer precursor mixture and a biocatalyst suspension “using techniques known in the art” (paragraph [00168] on page 55). Thus PEGDA is suitable for the intended uses of instant claim 1 of ‘configured to form a first emulsion with the whole cells, and configured to form a second emulsion with an aqueous carrier fluid in response to immersion of droplets of the first emulsion in the aqueous carrier fluid.’
As such, Kajiwara teaches a mixture comprising:
at least one photoinitiator (benzoyl peroxide);
a plurality of whole cells; and
at least one polymer precursor configured to form a first emulsion with the whole cells, and configured to form a second emulsion with an aqueous carrier fluid in response to immersion of droplets of the first emulsion in the aqueous carrier fluid (polyethylene glycol diacrylate, i.e. PEGDA).
Since the mixture of Kajiwara is polymerized for entrapping the cells in the polymer, then the mixture is directed to the claimed ‘mixture for forming polymer-encapsulated whole cells.’
Kajiwara differs from the claimed invention in that Kajiwara does not expressly disclose that the whole cells include a biocatalyst, the biocatalyst being operable to convert a C1-C3 hydrogen-comprising target gas to a product, wherein the C1-C3 hydrogen-comprising target gas is selected from the group consisting of: methane, ethane, ethylene, propane, and propylene.
Yu discloses that the single-step oxidation of methane to methanol is catalyzed by the NADH-dependent methane monooxygenase (MMO) in methanotrophs (page 609, first paragraph). Methane is underutilized as an energy source due to the lack of an efficient method to convert it to liquid form, e.g. methanol, for easy transportation (page 609, second paragraph). The nonspecific nature of MMO may be explored to facilitate the transformation of methane to methanol (page 609, second paragraph). The use of whole cells of methanotrophs has been explored since MMO is advantageously more stable in the cells than in extracts or in the purified form (page 609, second paragraph). In the study of Yu, cells of a methanotroph were immobilized to serve as a biocatalyst in the production of methanol from methane (page 610, second paragraph). The methanotroph with the highest MMO activity of the study was Methylomonas sp. Z201 which was found to have propylene oxidation activity, wherein the product is propylene oxide (page 611, last paragraph; page 613, last paragraph). Thus, the cells of that methanotroph are also operative to catalyze propylene, meeting the limitation of instant claim 26.
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to immobilize whole cells of a methanotroph (e.g. Methylomonas sp. Z201) when performing the invention of Kajiwara. One of ordinary skill in the art would have been motivated to do this because: (i) it would provide the enzyme MMO that catalyzes the transformation of methane to methanol for easy transformation, thereby improving the utilization of methane as an energy source; (ii) the use of whole cells of methanotrophs has been explored to stabilize MMO; and (iii) the immobilization of methanotrophs has been investigated (e.g. Yu). The immobilization of whole cells of a methanotroph to provide an enzyme (MMO) addresses the immobilization of an enzyme in the form of cells that is sought in Kajiwara. There would have been a reasonable expectation of entrapping whole cells of a methanotroph by the invention of Kajiwara because other cells had been successfully immobilized in Kajiwara, and Kajiwara teaches performing their invention with live or dried microorganic cells in general (e.g. column 3, lines 49-55). Whole cells of a methanotroph (e.g. Methylomonas cp. Z201 of Yu) are directed to whole cells that include a biocatalyst, the biocatalyst being operable to convert a C1-C3 hydrogen-comprising target gas to a product, wherein the C1-C3 hydrogen-comprising target gas is selected from methane and propylene, meeting a limitation of instant claim 1. Therefore, Kajiwara in view of Yu (as evidenced by Goodman and Shum) renders obvious instant claims 1, 2 (polyethylene glycol diacrylate), 3, 7 (methane or propylene is the chemical reactant that is a gas; methanol or propylene oxide is the product which is a liquid), 8, 9 (methanotrophic organism), and 26.
Regarding instant claim 4, the references differ from the claimed invention in that Kajiwara does not expressly disclose that the concentration of the PEGDA #4 in Examples 7 and 8 (directed to the ‘at least one polymer precursor’) is in a range of about 0.1 weight% to about 90 weight% of a total weight of the mixture. However, Kajiwara discloses that the amount of the polymerizable monomer or prepolymer to be contained in the organic solvent being used as the dispersant for the enzyme powder is in the range of 0.5 to 30% by weight (column 5, lines 61-65). In performing the invention of Kajiwara (in particular, using the polymer precursor and initiator of Examples 7 and 8) in view of Yu, it would have been within the purview of the skilled artisan to apply that teaching of Kajiwara. Given the low weights of the other components in the mixture of Examples 7 and 8 as compared to the mass of the PEGDA (e.g. 5 mg benzoyl peroxide as compared to 400 g of PEGDA #400; see column 12, lines 59-64 and column 13, lines 40-45), then it would have been obvious that modifying the weight percentage of the prepolymer (PEGDA) according to the teaching in column 5, lines 61-65 of Kajiwara would yield a weight percentage of the prepolymer to the total weight of the mixture that falls within the claimed range of about 0.1 weight% to about 90 weight% of the total weight of the mixture. Thus, instant claim 4 is rendered obvious.
Regarding instant claim 5, the references differ from the claimed invention in that Kajiwara does not expressly disclose that the polymer precursor (PEGDA #400) has a molecular weight in a range of about 500 Daltons to about 500,000 Daltons. However, Kajiwara discloses in Example 5 using PEGDA #400 and polyethylene glycol dimethacrylate #600 (PEGDMA #600) for the immobilization of an enzyme in which benzoyl peroxide is included as a polymerization initiator (column 10, lines 45-56). In performing the invention of Kajiwara in view of Yu, it would have been obvious to the person of ordinary skill in the art to substitute PEGDA #400 with PEGDMA #600 in the mixture comprising the cells because PEGDMA #600 was recognized in Example 5 of Kajiwara for immobilization of an enzyme in which the same polymerization initiator, benzoyl peroxide, is used (column 11, lines 16-24) and because Kajiwara discloses polyethylene glycol dimethacrylate as a monomer that may be used for immobilizing an enzyme (as discussed above, the enzyme can be provided as cells); see claims 1 and 7 of Kajiwara. There would have been a reasonable expectation of immobilizing the cells by this modification because of Example 5 of Kajiwara and because of the broader teachings of Kajiwara (e.g. claims 1 and 7 of Kajiwara). As evidenced by Killion, PEGDMA 600 has the molecular weight of 600 Daltons (page 1220, right column, second full paragraph). The molecular weight of 600 Daltons falls within the range of instant claim 5. For the reasons set forth above with respect to PEGDA in Examples 7 and 8 of Kajiwara (rejection of instant claim 1, citing column 4, lines 17-25 and 62-66 and column 5, lines 21-24 regarding the emulsion of the Kajiwara; PEGDMA is a methacrylic ester, see claim 7 of Kajiwara), PEGDMA #600 is directed to ‘at least one polymer precursor configured to form a first emulsion with the whole cells’ as recited in instant claim 1. As evidenced by Menner, PEGDMA has been known for being capable of being in an emulsion with an aqueous phase (abstract; page 7629, right column, second to fourth paragraphs). Therefore, PEGDMA #600 is suitable for the claimed intended use as set forth by the limitation of instant claim 1 of ‘at least one polymer precursor…configured to form a second emulsion with an aqueous carrier fluid in response to immersion of droplets of the first emulsion in the aqueous carrier fluid.’ As such, in using PEGDMA #600 in the invention rendered obvious by Kajiwara in view of Yu, then instant claim 5 is rendered obvious.
Regarding instant claim 6, the cells in Example 7 of Kajiwara are live whole cells, and the cells in Example 8 are freeze dried cells (column 13, lines 35-38). Thus, in performing the invention rendered obvious by Kajiwara in view of Yu, it would have been obvious to provide the whole cells of a methanotroph as live whole cells or freeze dried cells. Freeze dried cells meet the claimed limitation of ‘dried whole cells.’ Thus, instant claim 6 is rendered obvious.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Kajiwara and Yu, as evidenced by Goodman, Shum, Killion, and Menner as applied to claims 1-9 and 26 above, and further in view of Morgan (Journal of Microbiological Methods. 2006. 66: 183-193. Listed on IDS filed 6/19/24).
As discussed above, Kajiwara in view of Yu (as evidenced by Goodman, Shum, Killion, and Menner) renders obvious claims 1-9 and 26. Regarding claim 23, the invention of Kajiwara in view of Yu meets limitations of the claimed invention (see discussion above with respect to claim 1). The references differ from claim 23 in that they do not expressly disclose that the whole cells of a methanotroph (directed to the claimed ‘whole cells’ that include a biocatalyst) include reconstituted whole cells.
Morgan discloses that freeze drying has been used to preserve microorganisms for decades and is the preferred method for culture collections worldwide (page 187, right column, second full paragraph). Freeze dried material allows easy and inexpensive shipping and handling (page 187, right column, second full paragraph). Furthermore, Morgan teaches that rehydration of freeze dried microorganisms is the final critical step for the revival of cells after drying (page 190, left column, second paragraph).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to use methanotroph cells that had previously been freeze-dried and rehydrated in the mixture rendered obvious by Kajiwara in view of Yu (as evidenced by Goodman, Shum, Killion, and Menner). One of ordinary skill in the art would have been motivated to do this because microorganisms are commonly preserved by freeze drying, freeze drying allows for easy and inexpensive shipping and handling of microorganisms (the methanotroph likely had to be shipped from one site to the skilled artisan performing the method; thus this would have been desirable), and rehydration of freeze-dried microorganisms is necessary in order to revive the cells. Therefore, instant claim 23 is rendered obvious.
Claims 1 and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over Kajiwara and Yu, as evidenced by Goodman, Shum, Killion, and Menner as applied to claims 1-9 and 26 above, and further in view of Patel (US 4,266,034. Previously cited).
As discussed above, Kajiwara in view of Yu (as evidenced by Goodman, Shum, Killion, and Menner) renders obvious claims 1-9 and 26. The references differ from claim 24 in that they do not expressly disclose that the whole cells of a methanotroph (directed to the claimed ‘whole cells’ that include a biocatalyst) are operative to catalyze ethylene. The references differ from claim 25 in that they do not expressly disclose that the whole cells of a methanotroph (directed to the claimed ‘whole cells’ that include a biocatalyst) are operative to catalyze ethane.
Patel discloses isolated methylotrophic microorganism strains and their natural and/or artificial mutants which are useful in converting C1-C6 alkanes to alcohols (particularly methane to methanol); C3-C6 alkanes to the corresponding C3-C6 alcohols and methyl ketones; and C2-C4 alkenes selected from a group that includes ethylene and propylene (abstract). See Table III in column 17 showing methylotrophic microorganism strains that convert methane to methanol, ethylene to ethylene oxide, and propylene to propylene oxide. See Table XXVII in column 47 showing two methylotrophic microorganism strains that convert methane to methanol, ethane to ethanol, and propane to different propanol products.
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to substitute the methanotroph with any of the methylotrophic microorganism strains of Patel when practicing the invention rendered obvious by Kajiwara in view of Yu (as evidenced by Goodman, Shum, Killion, and Menner). It would have been an obvious matter of simple substitution of one microorganism that converts methane to methanol for another. There would have been a reasonable expectation of entrapping whole cells of the methylotrophic microorganism strains of Patel by the invention rendered obvious by Kajiwara and Yu (as evidenced by Goodman, Shum, Killion, and Menner) because other cells had been successfully immobilized in Kajiwara, and Kajiwara teaches performing their invention with live or dried microorganic cells in general (e.g. column 3, lines 49-55). In making the substitution, then the references render obvious inclusion of whole cells that include a biocatalyst, the biocatalyst being operable to convert a C1-C3 hydrogen-comprising target gas to a product, wherein the C1-C3 hydrogen-comprising target gas is selected from the group consisting of: methane, ethane, ethylene, propane, and propylene (all embodiments of instant claim 1). The references further render obvious the limitations of instant claims 24-26. Thus, instant claims 1 and 24-26 are rendered obvious.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Kajiwara and Yu, as evidenced by Goodman, Shum, Killion, and Menner as applied to claims 1-9 and 26 above, and further in view of Reed (US 2010/0120104. Previously cited).
As discussed above, Kajiwara in view of Yu (as evidenced by Goodman, Shum, Killion, and Menner) renders obvious claims 1-9 and 26. Regarding claim 27, the mixture comprising whole cells (P. xylosa), PEGDA, and benzoyl peroxide as taught in Examples 7 and 8 of Kajiwara (column 12, lines 50-66; column 13, lines 35-46) necessarily has to be provided in a container – a container is directed to a ‘bioreactor.’ The references differ from claim 27 in that they do not expressly disclose that the bioreactor rendered obvious by the references is configured to catalyze CO2 to a synthetic fuel.
Reed discloses compositions and methods for a multistep biological and chemical process for the capture and conversion of carbon dioxide into organic chemicals including biofuels (abstract). In particular, the invention utilizes obligate or facultative chemoautotrophic microorganisms (paragraph [0060]-[0061]). The chemoautotrophic microorganisms are immobilized within their growth environment, including growing the microorganisms on a matrix, mesh, or membrane made from polymers (paragraph [0104]).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to additionally immobilize whole cells of at least one of the chemoautotrophic microorganisms disclosed by Reed when performing the invention rendered obvious by Kajiwara in view of Yu (as evidenced by Goodman, Shum, Killion, and Menner). One of ordinary skill in the art would have been motivated to do this in order to convert carbon dioxide into biofuels (directed to the claimed ‘synthetic fuel’) which is a desirable product, and because Reed teaches the immobilization of their microorganisms. There would have been a reasonable expectation of entrapping whole cells of at least one of Reed’s chemoautotrophic microorganisms by the invention rendered obvious by Kajiwara and Yu (as evidenced by Goodman, Shum, Killion, and Menner) because other cells had been successfully immobilized in Kajiwara, and Kajiwara teaches performing their invention with live or dried microorganic cells in general (e.g. column 3, lines 49-55). In further immobilizing cells of Reed’s chemoautotrophic microorganism(s), then the bioreactor rendered obvious by the references is configured to catalyze CO2 to a synthetic fuel. Thus, instant claim 27 is rendered obvious.
Claims 1-10, 26, 28, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Franco (Acta Biomaterialia. 2011. 7: 3267-3276. Previously cited) in view of Yu (Annals of the New York Academy of Sciences. 1998. 864(1): 609-615. Previously cited).
Franco discloses a novel, dual-photoinitiator technique for encapsulation of cells within hydrogel microspheres (abstract). For the microencapsulation of a cell culture, cells were suspended in a sterile polymer solution comprising 10% PEG-PQ-PEG in HBS (HEPES buffered saline, see page 3268, right column, third paragraph) and eosin Y, and further containing PEG-RGDS (page 3270, left column, second paragraph). PEG-PQ-PEG and PEG-RGDS are each directed to a ‘polymer precursor’ as claimed. Also, eosin Y is a photoinitiator (page 3268, right column, third paragraph).
After preparation of the suspension in polymer solution, microspheres were generated using an I651 stock solution in the mineral oil and purified with media washes according to Franco’s described protocol (page 3270, left column, second paragraph). I651, i.e. 2,2-dimethoxy-2-phenyl acetophenone, is a photoinitiator used to initiate crosslinking (page 3269, left column, first full paragraph). When describing their protocol, Franco teaches that microspheres are generated by generating an emulsion of the liquid polymer solution in mineral oil via vortexing (page 3268, left column, third paragraph and right column, last paragraph). See also Figure 3 on page 3271.
Since an emulsion was prepared of the cell suspension in polymer solution, then the polymer precursors (PEG-PQ-PEG, PEG-RGDS) in the polymer solution of Franco are configured to form a first emulsion with the whole cells, meeting a limitation of instant claim 1. Regarding the limitation of instant claim 1 of ‘at least one polymer precursor…configured to form a second emulsion with an aqueous carrier fluid in response to immersion of droplets of the first emulsion in the aqueous carrier fluid,’ it is directed to an intended use of the at least one polymer precursor. Since the polymer solution of Franco is an aqueous solution comprising the polymer precursors (due to it comprising HEPES buffered saline) that can form an emulsion, then the polymer precursors of Franco (PEG-PQ-PEG, PEG-RGDS) are suitable for the claimed intended use regarding forming a second emulsion. Moreover, instant claim 1 does not require that the mixture comprises a second emulsion formed by immersing droplets of the first emulsion in an aqueous carrier. The instant claims do not require that the mixture comprises a first emulsion and/or a second emulsion.
As such, Franco meets limitations of the claimed invention by disclosing a mixture for forming polymer-encapsulated whole cells, the mixture comprising:
at least one photoinitiator (eosin Y);
a plurality of whole cells; and
at least one polymer precursor configured to form a first emulsion with the whole cells, and configured to form a second emulsion with an aqueous carrier fluid in response to immersion of droplets of the first emulsion in the aqueous carrier fluid (PEG-PQ-PEG, PEG-RGDS).
Franco differs from the claimed invention in that Franco does not expressly disclose that the whole cells include a biocatalyst, the biocatalyst being operable to convert a C1-C3 hydrogen-comprising target gas to a product, wherein the C1-C3 hydrogen-comprising target gas is selected from the group consisting of: methane, ethane, ethylene, propane, and propylene.
Yu discloses that the single-step oxidation of methane to methanol is catalyzed by the NADH-dependent methane monooxygenase (MMO) in methanotrophs (page 609, first paragraph). Methane is underutilized as an energy source due to the lack of an efficient method to convert it to liquid form, e.g. methanol, for easy transportation (page 609, second paragraph). The nonspecific nature of MMO may be explored to facilitate the transformation of methane to methanol (page 609, second paragraph). The use of whole cells of methanotrophs has been explored since MMO is advantageously more stable in the cells than in extracts or in the purified form (page 609, second paragraph). In the study of Yu, cells of a methanotroph were immobilized to serve as a biocatalyst in the production of methanol from methane (page 610, second paragraph). The methanotroph with the highest MMO activity of the study was Methylomonas sp. Z201 which was found to have propylene oxidation activity, wherein the product is propylene oxide (page 611, last paragraph; page 613, last paragraph). Thus, the cells of that methanotroph are also operative to catalyze propylene, meeting the limitation of instant claim 26.
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to encapsulate whole cells of a methanotroph (e.g. Methylomonas sp. Z201) when performing the invention of Franco. One of ordinary skill in the art would have been motivated to do this because: (i) it would provide the enzyme MMO that catalyzes the transformation of methane to methanol for easy transformation, thereby improving the utilization of methane as an energy source; (ii) the use of whole cells of methanotrophs has been explored to stabilize MMO; and (iii) the immobilization of methanotrophs has been investigated (e.g. Yu). There would have been a reasonable expectation of encapsulating whole cells of a methanotroph by the invention of Franco because other cells had been successfully immobilized in Franco. Whole cells of a methanotroph (e.g. Methylomonas cp. Z201 of Yu) are directed to whole cells that include a biocatalyst, the biocatalyst being operable to convert a C1-C3 hydrogen-comprising target gas to a product, wherein the C1-C3 hydrogen-comprising target gas is selected from methane and propylene, meeting a limitation of instant claim 1. Therefore, Franco in view of Yu renders obvious instant claims 1, 6 (live whole cells), 7 (methane or propylene is the chemical reactant that is a gas; methanol or propylene oxide is the product which is a liquid), 8, 9 (methanotrophic organism), and 26.
Regarding instant claims 2 and 3, Franco discloses that PEG-PQ-PEG comprises an MMP-sensitive peptide PQ (page 3268, right column, second paragraph). Franco explains that in the PEG-PQ-PEG, the MMP-sensitive peptide was embedded in the backbone of the PEGDA chains (page 3274, left column, second paragraph). Therefore, PEG-PQ-PEG is directed to polyethylene glycol diacrylate (PEGDA) of instant claims 2 and 3. Also, Franco discloses that PEG-RGDS comprises RGDS peptide (page 3268, right column, first paragraph). Given PEG in the polymer precursor, PEG-RGDS is directed to polyethylene glycol (PEG) of instant claim 2. Additionally, Franco teaches another embodiment of microencapsulation of cells in which the polymer solution comprises 10% PEGDA in HBS (i.e. HEPES buffered saline) instead of PEG-PQ-PEG (page 3270, left column, first paragraph). That embodiment also meets the polyethylene glycol diacrylate limitation of instant claims 2 and 3. Thus, instant claims 2 and 3 are rendered obvious.
Regarding instant claim 4, PEG-PQ-PEG is present at 10 wt.% concentration of the HBS (page 3269, left column, third paragraph; page 3268, right column, third paragraph describing the hydrogel precursor solution of Franco). Since 10 wt.% falls within the claimed range, then instant claim 4 is rendered obvious.
Regarding instant claim 5, Franco teaches another embodiment of microencapsulation of cells in which the polymer solution comprises 10% PEGDA in HBS (i.e. HEPES buffered saline) instead of PEG-PQ-PEG (page 3270, left column, first paragraph). The PEGDA has a molecular weight of 10 kDa, i.e. 10,000 Da (page 3269, left column, first full paragraph). Since the molecular weight of 10,000 Da falls within the claimed range, then instant claim 5 is rendered obvious.
Regarding instant claim 10, since I651 initiates crosslinking in Franco (page 3269, left column, first full paragraph), then I651 is directed to a ‘crosslinking initiator’ as claimed. In providing the cell suspension (comprising the polymer solution) in I651 stock solution in mineral oil (page 3270, left column, second paragraph), then the mixture further comprises a crosslinking initiator (I651). Thus, instant claim 10 is rendered obvious.
Regarding instant claim 28, HBS (HEPES buffered saline) of the cell suspension in polymer solution of Franco (page 3270, left column, second paragraph) is directed to an aqueous carrier fluid. Thus, instant claim 28 is rendered obvious.
Regarding instant claim 29, Franco in view of Yu does not expressly disclose that the aqueous carrier fluid (HBS, with or without the other components, TEOA and NVP; see page 3270, left column, second paragraph of Franco) comprises water present in an amount from about 50 wt% to about 60 wt% of a total weight of the aqueous carrier fluid. However, it would have been an obvious matter of routine experimentation to vary the amount of water in the aqueous carrier fluid to ensure that an appropriate emulsion is obtained. Thus, instant claim 29 is rendered obvious.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Franco and Yu as applied to claims 1-10, 26, 28, and 29 above, and further in view of Morgan (Journal of Microbiological Methods. 2006. 66: 183-193. Listed on IDS filed 6/19/24).
As discussed above, Franco in view of Yu renders obvious claims 1-10, 26, 28, and 29. Regarding claim 23, the invention of Franco in view of Yu meets limitations of the claimed invention (see discussion above with respect to claim 1). The references differ from claim 23 in that they do not expressly disclose that the whole cells of a methanotroph (directed to the claimed ‘whole cells’ that include a biocatalyst) include reconstituted whole cells.
Morgan discloses that freeze drying has been used to preserve microorganisms for decades and is the preferred method for culture collections worldwide (page 187, right column, second full paragraph). Freeze dried material allows easy and inexpensive shipping and handling (page 187, right column, second full paragraph). Furthermore, Morgan teaches that rehydration of freeze dried microorganisms is the final critical step for the revival of cells after drying (page 190, left column, second paragraph).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to use methanotroph cells that had previously been freeze-dried and rehydrated in the mixture rendered obvious by Franco in view of Yu. One of ordinary skill in the art would have been motivated to do this because microorganisms are commonly preserved by freeze drying, freeze drying allows for easy and inexpensive shipping and handling of microorganisms (the methanotroph likely had to be shipped from one site to the skilled artisan performing the method; thus this would have been desirable), and rehydration of freeze-dried microorganisms is necessary in order to revive the cells. Therefore, instant claim 23 is rendered obvious.
Claims 1 and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over Franco and Yu as applied to claims 1-10, 26, 28, and 29 above, and further in view of Patel (US 4,266,034. Previously cited).
As discussed above, Franco in view of Yu renders obvious claims 1-10, 26, 28, and 29. The references differ from claim 24 in that they do not expressly disclose that the whole cells of a methanotroph (directed to the claimed ‘whole cells’ that include a biocatalyst) are operative to catalyze ethylene. The references differ from claim 25 in that they do not expressly disclose that the whole cells of a methanotroph (directed to the claimed ‘whole cells’ that include a biocatalyst) are operative to catalyze ethane.
Patel discloses isolated methylotrophic microorganism strains and their natural and/or artificial mutants which are useful in converting C1-C6 alkanes to alcohols (particularly methane to methanol); C3-C6 alkanes to the corresponding C3-C6 alcohols and methyl ketones; and C2-C4 alkenes selected from a group that includes ethylene and propylene (abstract). See Table III in column 17 showing methylotrophic microorganism strains that convert methane to methanol, ethylene to ethylene oxide, and propylene to propylene oxide. See Table XXVII in column 47 showing two methylotrophic microorganism strains that convert methane to methanol, ethane to ethanol, and propane to different propanol products.
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to substitute the methanotroph with any of the methylotrophic microorganism strains of Patel when practicing the invention rendered obvious by Franco in view of Yu. It would have been an obvious matter of simple substitution of one microorganism that converts methane to methanol for another. There would have been a reasonable expectation of encapsulating whole cells of the methylotrophic microorganism strains of Patel by the invention rendered obvious by Franco and Yu since other cells had been successfully immobilized in Franco. In making the substitution, then the references render obvious inclusion of whole cells that include a biocatalyst, the biocatalyst being operable to convert a C1-C3 hydrogen-comprising target gas to a product, wherein the C1-C3 hydrogen-comprising target gas is selected from the group consisting of: methane, ethane, ethylene, propane, and propylene (all embodiments of instant claim 1). The references further render obvious the limitations of instant claims 24-26. Thus, instant claims 1 and 24-26 are rendered obvious.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Franco and Yu as applied to claims 1-10, 26, 28, and 29 above, and further in view of Reed (US 2010/0120104. Previously cited).
As discussed above, Franco in view of Yu renders obvious claims 1-10, 26, 28, and 29. Regarding claim 27, Figure 3 on page 3271 of Franco shows that the mixture comprising cells and polymer solution is provided in a glass test tube – a glass test tube is directed to a ‘bioreactor.’ The references differ from claim 27 in that they do not expressly disclose that the bioreactor rendered obvious by the references is configured to catalyze CO2 to a synthetic fuel.
Reed discloses compositions and methods for a multistep biological and chemical process for the capture and conversion of carbon dioxide into organic chemicals including biofuels (abstract). In particular, the invention utilizes obligate or facultative chemoautotrophic microorganisms (paragraph [0060]-[0061]). The chemoautotrophic microorganisms are immobilized within their growth environment, including growing the microorganisms on a matrix, mesh, or membrane made from polymers (paragraph [0104]).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to additionally encapsulate whole cells of at least one of the chemoautotrophic microorganisms disclosed by Reed when performing the invention rendered obvious by Franco in view of Yu. One of ordinary skill in the art would have been motivated to do this in order to convert carbon dioxide into biofuels (directed to the claimed ‘synthetic fuel’) which is a desirable product, and because Reed teaches the immobilization of their microorganisms. There would have been a reasonable expectation of encapsulating whole cells of at least one of Reed’s chemoautotrophic microorganisms by the invention rendered obvious by Franco in view of Yu since other cells had been successfully immobilized in Franco. In further immobilizing cells of Reed’s chemoautotrophic microorganism(s), then the bioreactor rendered obvious by the references is configured to catalyze CO2 to a synthetic fuel. Thus, instant claim 27 is rendered obvious.
Response to Arguments
Applicant’s arguments, filed May 6, 2026, with respect to the rejection under 35 U.S.C. 103 of claim 23 as being unpatentable over Oh in view of Yu and Morgan, have been fully considered and are persuasive. The rejection has been overcome by the amendment to claim 23 requiring “at least one photoinitiator.” The curing agent of Oh is not a photoinitiator. Therefore, this rejection has been withdrawn.
However, Applicant’s arguments are not persuasive with respect to the rejections under 35 U.S.C. 103 based on Kajiwara and Franco as primary references; these rejections have been modified above as necessitated by the amendments to the claims. Applicant argues that Kajiwara creates a gel in an organic solvent that encapsulates the materials, then removes the organic solvent after curing. Applicant argues that this is in sharp contrast with claim 1 which includes at least one polymer precursor configured to form a first emulsion with the whole cells, and configured to form a second emulsion with an aqueous carrier fluid in response to immersion of droplets of the first emulsion in the aqueous carrier fluid, thereby enabling formation of discrete capsules, citing Figure 15 and related description in the instant application. However, in reciting “at least one polymer precursor configured to form a first emulsion with the whole cells,” claim 1 does not require that the mixture comprises a first emulsion of the at least one polymer precursor and the whole cells. It sets forth an intended use and a functional property of the at least one polymer precursor. Also, the claimed limitation of “at least one polymer precursor…configured to form a second emulsion with an aqueous carrier fluid in response to immersion of droplets of the first emulsion in the aqueous carrier fluid” sets forth an intended use of the at least one polymer precursor. Claim 1 does not require that the mixture comprises the second emulsion. Therefore, the claims remain rejected over Kajiwara in view of Yu (as evidenced by Goodman, Shum, Killion, and Menner), as well as further in view of Morgan, Patel, or Reed.
Regarding the rejections under 35 U.S.C. 103 based on Franco as the primary reference, Applicant asserts that claim 1 as amended distinguishes from Franco in view of Yu, given that Franco forms the spheres in mineral oil while components of the claimed composition are specifically configure to form the two recited emulsions, thereby enabling formation of capsules in aqueous carrier fluid. However, since Franco teaches generating an emulsion of the liquid polymer solution in mineral oil (page 3628, left column, third paragraph and right column, last paragraph), then the polymer precursors of the liquid polymer solution are “configured to form a first emulsion with the whole cells” as recited in instant claim 1. Regarding the claimed limitation of “at least one polymer precursor…configured to form a second emulsion with an aqueous carrier fluid in response to immersion of droplets of the first emulsion in the aqueous carrier fluid,” it sets forth an intended use of the at least one polymer precursor. The polymer precursors of the polymer solution are suitable for forming an emulsion in an aqueous carrier fluid since they can form an emulsion with water as present in the HBS (HEPES buffered saline). Therefore, they are suitable for the claimed intended use regarding a second emulsion. Moreover, claim 1 does not require that the mixture comprises a first emulsion and/or a second emulsion. Therefore, the claims remain rejected over Franco in view of Yu, and also further in view of Morgan, Patel, or Reed.
Conclusion
Claims 1-10 and 23-29 are rejected.
Claim 30 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 21 and 22 are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SUSAN E. FERNANDEZ/ Examiner, Art Unit 1651
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