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 .
Status of Claims
Claims 1, 4-5, 15-28 and 30-33 are pending following the Reply filed 06/30/2026. Claims 1, 5 and 30-31 have been amended. Claim 29 has been cancelled. Claims 32-33 have been added without introducing new matter. Claims 1, 4-5, 15-28 and 30-33 are presently considered.
Notice
The examiner notes the following error in the amended claim set:
Claim 31 indicates a status of “previously presented” but has been amended in line 4.
Per 37 C.F.R. 1.121 (see section (c)(2)), all claims being currently amended in an
amendment paper shall be presented in the claim listing, indicate a status of "currently
amended," and be submitted with markings to indicate the changes that have been made relative
to the immediate prior version of the claims.
Since the above-mentioned reply appears to be bona fide, and no other errors or omissions appear in the pending claim set, examination of the claims has proceeded on the merits. Therefore, claim 31 is treated as an amended claim.
Withdrawn
Any objection or rejection of claim 29 is moot because the claim has been cancelled.
The objections to claims 5 and 30 are withdrawn in light of the amendments.
Claim Objections
Claim 1 is objected to because of the following informalities:
The term “RRE” in line 23 appears to be a typographical error. Please amend this term to recite “REE”.
The term “RRE” in line 25 appears to be a typographical error. Please amend this term to recite “REE”.
The term “RRE” in line 28 appears to be a typographical error. Please amend this term to recite “REE”.
The term “phenotypic” in line 24 appears to be a typographical error. Please amend this term to recite “phenotype”.
The term “phenotypic” in line 25 appears to be a typographical error. Please amend this term to recite “phenotype”.
Appropriate correction is required.
Claim 32 is objected to because of the following informalities:
The term “RRE” in line 20 appears to be a typographical error. Please amend this term to recite “REE”.
The term “RRE” in line 22 appears to be a typographical error. Please amend this term to recite “REE”.
The term “RRE” in line 24 appears to be a typographical error. Please amend this term to recite “REE”.
The term “phenotypic” in line 21 appears to be a typographical error. Please amend this term to recite “phenotype”.
The term “phenotypic” in line 22 appears to be a typographical error. Please amend this term to recite “phenotype”.
Appropriate correction is required.
Claim Interpretation
Amended claim 1(a) recites the limitation “wherein in (i), (ii), and (iii) the plurality of methane-capturing bioagents comprise a plurality of chemically altered halophilic methanotroph bacterial cells” which is the result of a product-by-process limitation:
wherein the plurality of phenotypically altered halophilic methanotroph bacterial cells are made by a process comprising: culturing a plurality of halophilic methanotroph bacterial cells in a medium comprising at least one rare earth element (RRE) for a sufficient time to modify the phenotypic of the plurality of halophilic methanotroph bacterial cells, wherein the RRE-modified phenotypic in the plurality of halophilic methanotroph bacterial cells comprises an altered redox balance in the plurality of RRE-modified, phenotypically altered halophilic methanotroph bacterial cells
The examiner maintains that this product-by-process limitation, even as presently amended, does not change the structure of the halophilic methanotroph bacterial cells, because an altered phenotype resulting purely from environmental culturing conditions is not a structural change in the bacterium itself, but merely a transient, functional change. While the declaration filed by Applicant on 03/30/2026 discusses the “chemical alteration” as a “metabolic shift” that results from the process step of culturing, there is no evidence that this change in metabolism is associated with any permanent structural change in the bacterium. It is understood that the bacteria possess multiple metabolic pathways, regardless of which is being expressed at a given time, and culturing conditions merely trigger the upregulation or downregulation of these pre-existing pathways. Therefore, the method step of culturing the bacteria with a rare earth element does not result in or imply a change in structure, only a transient change in function that is an inherent property of the bacterium.
Newly added claim 32(a) is nearly identical to claim 1(a), except the claim does not recite “cartridges” in part “(i)” nor does it recite “wherein the plurality of nanoshells or the crystal gel matrix comprise: CdSe nanoparticles coated with CdS or ZnTE, or CdTe nanoparticles coated with CdSe”. Therefore, the “chemically altered” or “phenotypically altered” methanotrophs of claim 32 are arrived at using the same product-by-process step recited in claim 1, which is not interpreted to result in any structural difference in the bacterial cells, as discussed above.
Maintained rejections and new rejections necessitated by amendment
Claim Rejections - 35 USC § 112(b)
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 1, 4-5, 15-28 and 30-33 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 1 recites the limitation "the plurality of phenotypically altered halophilic methanotroph bacterial cells" in line 20. There is insufficient antecedent basis for this limitation in the claim.
Suggestion to obviate the basis for rejection above: Applicant may, for example, amend the term “chemically” in line 18 to recite “phenotypically” to provide antecedent basis.
Claim 1 recites the limitation “wherein the RRE-modified phenotypic in the plurality of halophilic methanotroph bacterial cells comprises an altered redox balance in the plurality of RRE-modified, phenotypically altered halophilic methanotroph bacterial cells” in lines 25-29. There is insufficient antecedent basis for the limitations of “the RRE-modified phenotypic” and “the plurality of RRE-modified, phenotypically altered halophilic methanotroph bacterial cells” in the claim.
Suggestion to obviate the basis for rejection above: Applicant may, for example, amend the entire limitation above to recite “wherein the phenotypically altered halophilic methanotroph bacterial cells comprise an altered redox balance”.
Claim 30(b) recites the limitation wherein “the nanoshells, arrays, macroparticles, nanoparticles, microfibers, microtubes, microribbons, microbeads, sheets, meshes, or cartridges of (a) are fabricated into modular units”, which renders the claim indefinite because this limitation depends from elements recited in limitation (a), which is recited in the alternative. Limitations recited in the alternative are normally treated as being mutually exclusive to one another, and this claim construction can lead to ambiguity when interpretating the claim.
In this case, the elements recited as starting materials (i.e., nanoshells, arrays, macroparticles, nanoparticles, microfibers, microtubes, microribbons) are recited in part (a) as being contained in or fabricated as end products (i.e., sheets, mats, meshes or cartridges). Therefore, it is unclear whether the starting materials (i.e., nanoshells, arrays, etc.) recited in part (b) also require the end products (i.e., sheets, mats, etc.) recited in part (a). For example, it is unclear whether the “nanoshells” of part (a) are required to be contained in or fabricated as “sheets, mats, meshes or cartridges” before being “fabricated into modular units”. Therefore, the reference to limitation “(a)” does not provide clear antecedent basis and renders the scope of the claim unclear.
Suggestion to obviate the basis for rejection above: Applicant may, for example, remove limitation “(b)” from the claim, add “modular units” to the list of end products recited in limitation “(a)”, and renumber limitation “(c)” to “(b)”. Applicant may also consider adding a further dependent claim to capture desired embodiment(s), so long as it does not introduce new matter.
Claim 30(c) recites the limitation wherein “the… meshes, or mats are fabricated into cartridges”. There is insufficient antecedent basis for this limitation in the claim. Note that the claim has been amended to depend from claim 32, which does not recite “meshes” or “mats”.
Suggestion to obviate the basis for rejection above: Applicant may, for example, remove the terms “meshes” and “mats” from the claim. Applicant may also consider adding a further dependent claim to capture desired embodiment(s), so long as it does not introduce new matter.
Claim 32 recites the limitation "the plurality of phenotypically altered halophilic methanotroph bacterial cells" in lines 17-18. There is insufficient antecedent basis for this limitation in the claim.
Suggestion to obviate the basis for rejection above: Applicant may, for example, amend the term “chemically” in line 15 to recite “phenotypically” to provide antecedent basis.
Claim 32 recites the limitation “wherein the RRE-modified phenotypic in the plurality of halophilic methanotroph bacterial cells comprises an altered redox balance in the plurality of RRE-modified, phenotypically altered halophilic methanotroph bacterial cells” in lines 22-25. There is insufficient antecedent basis for the limitations of “the RRE-modified phenotypic” and “the plurality of RRE-modified, phenotypically altered halophilic methanotroph bacterial cells” in the claim.
Suggestion to obviate the rejection: Applicant may, for example, amend the entire limitation above to recite “wherein the phenotypically altered halophilic methanotroph bacterial cells comprise an altered redox balance”.
Claims 4-5, 15-28, 30-31 and 33 are also rejected for depending from an indefinite claim and for failing to rectify the indefiniteness of the claim(s) from which they depend.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 15-17, 25-27 and 32-33 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lidstrom et al., US 20170081686 A1 (cited in the IDS filed 01/14/2022), hereafter, “Lidstrom”, as evidenced by Orata et al. (Phylogenomic Analysis of the Gammaproteobacterial Methanotrophs (Order Methylococcales) Calls for the Reclassification of Members at the Genus and Species Levels, Front. Microbiol. 9:3162, published 12/19/2018; previously cited).
Regarding claim 1, Lidstrom teaches compositions comprising methanotrophic bacteria that function by removing gaseous methane (see Abstract; pg. 2, para. [0027]) from a gaseous substrate (see pg. 2, para. [0020]). Lidstrom teaches a methane fermentation bioreactor, comprising a plurality of solid supports comprising immobilized, viable methanotrophic bacteria (see claim 22) wherein the solid supports comprise polymers (see pg. 2, para. [0025]) which the bacteria are attached to (see pg. 12, para. [0132]). Lidstrom teaches the methanotrophs are halophilic (see pg. 7, para. [0091]). Hence, Lidstrom teaches a product of manufacture (methane fermentation bioreactor) for the removal of gaseous methane from a sample comprising gaseous methane (substrate), wherein the product of manufacture contains a plurality of methane-capturing bioagents (halophilic methanotrophic bacteria), which are immobilized in a polymer, as recited in part (iii) of the claim.
Regarding the limitation, “wherein in steps (i), (ii), and (iii) the plurality of methane-capturing bioagents comprise a plurality of chemically altered halophilic methanotroph bacterial cells”, this limitation is interpreted to be a functional limitation that does not change the structure of the halophilic methanotroph bacterial cells. As discussed under Claim Interpretation, the ”chemically altered” or “phenotypically altered” bacterial cells are the functional result of a product-by-process step that does not result in any change in structure.
Regarding the limitation, “wherein the plurality of phenotypically altered halophilic methanotroph bacterial cells are made by a process comprising: culturing a plurality of halophilic methanotroph bacterial cells in a medium comprising at least one rare earth element (RRE) for a sufficient time to modify the phenotypic of the plurality of halophilic methanotroph bacterial cells, wherein the RRE-modified phenotypic in the plurality of halophilic methanotroph bacterial cells comprises an altered redox balance in the plurality of RRE-modified, phenotypically altered halophilic methanotroph bacterial cells”, this limitation is a product-by-process step which does not limit the structure of the claimed product. "[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." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP 2113. As discussed under Claim Interpretation this product-by-process step does not imply a structural change in the bacteria.
Regarding the limitation of part (b), Lidstrom teaches the bioreactor further comprises an inlet for supplying a mixture of methane and air (see pg. 2, para. [0028]) and an outlet designed and arranged in conjunction with the inlet to permit a flow of methane and air over or through the supports during methane fermentation (see pg. 2, para. [0029]). Hence, Lidstrom teaches the product of manufacture to comprise an input for injecting the sample and an output for removing the methane-depleted sample.
Regarding claim 15, Lidstrom teaches the methanotroph may include Methylomicrobium alcaliphilum 20Z (see pg. 3, para. [0057]). In view of Orata et al., Methylomicrobium alcaliphilum is the same species as Methylotuvimicrobium alcaliphilum (see Abstract).
Regarding claim 16, Lidstrom teaches the methanotroph may include Methylomicrobium buryatense 5G (see pg. 3, para. [0041]). In view of Orata et al., Methylomicrobium buryatense is the same species as Methylotuvimicrobium buryatense (see Abstract).
Regarding claim 17, Lidstrom teaches the bacteria to comprise halophilic methanotrophs, which include Methylomicrobium alcaliphilum 20Z (see pg. 8, para. [0092]). In view of Orata et al., Methylomicrobium alcaliphilum is the same species as Methylotuvimicrobium alcaliphilum (see Abstract).
Regarding claim 25, the further limitation of “wherein the media comprising a rare earth element comprises lanthanum” refers to a product-by-process step which does not limit the structure of the claimed product, as discussed regarding claim 1. Hence, the claim is anticipated by Lidstrom.
Regarding claim 26, the further limitation of “wherein the media further comprises calcium, copper or tungsten” refers to a product-by-process step which does not limit the structure of the claimed product, as discussed regarding claim 1. Hence, the claim is anticipated by Lidstrom.
Regarding claim 27, Lidstrom teaches the methanotroph may include Methylomicrobium alcaliphilum 20Z (see pg. 3, para. [0057]).
Regarding claim 32, Lidstrom teaches a product of manufacture (methane fermentation bioreactor) comprising (iii) a plurality of methane-capturing bioagents (halophilic methanotrophic bacteria) immobilized in a polymer, as discussed regarding claim 1. The limitations of claim 32(a) are nearly identical to claim 1(a), except claim 32 does not recite “cartridges” in part “(i)” nor does it recite “wherein the plurality of nanoshells or the crystal gel matrix comprise: CdSe nanoparticles coated with CdS or ZnTE, or CdTe nanoparticles coated with CdSe”. Therefore, Lidstrom teaches meets the limitations of part “(a)” for the same reasons discussed regarding claim 1.
Regarding the limitation of part (b), Lidstrom teaches the bioreactor further comprises an inlet for supplying a mixture of methane and air (see pg. 2, para. [0028]) (i.e., a sample input) and an outlet designed and arranged in conjunction with the inlet to permit a flow of methane and air over or through the supports during methane fermentation (see pg. 2, para. [0029]). The “sample” of part “(b)” is understood to be the “sample comprising gaseous methane” recited in the preamble. Hence, Lidstrom teaches the product of manufacture to comprise a “sample input” and a “gas output”.
Regarding claim 33, Lidstrom teaches the methanotroph may include Methylomicrobium alcaliphilum 20Z (see pg. 3, para. [0057]).
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.
Claims 1, 4-5, 15-18, 25-28 and 30-33 are rejected under 35 U.S.C. 103 as being unpatentable over Lidstrom, as evidenced by Orata et al., as applied to claims 1, 15-17, 25-27 and 32-33 above, and further in view of Liu et al. (previously cited), hereafter, “Liu”.
Regarding claim 1, Lidstrom teaches compositions comprising methanotrophic bacteria that ferment methane, wherein the viable methanotrophic bacteria are attached to and immobilized in a plurality of polymeric supports, as discussed above.
Lidstrom does not explicitly teach (i) the plurality of methane-capturing bioagents attached to or contained in a plurality of macroparticles, nanoparticles, arrays, sheets, microfibers, microtubes, microribbons or microbeads.
Liu teaches the use of triblock polymer fibers to encapsulate and immobilize microbes which remain viable and metabolically active for several months and can be used in various applications (see Abstract). Liu teaches that microorganisms most often exist in nature as biofilms which are formed by self-encapsulation in a self-developed extracellular polymeric matrix (see pg. 14201, col. 1, para. 1). Liu teaches that researchers are presently attempting to create synthetic biofilms and to exploit them for biotechnological applications in areas such as environmental remediation (see pg. 14201, col. 1, para. 1). Liu teaches that the formation of composite microbiological material containing entire microbial cells acting as catalytic centers has been pursued for several decades, and in almost all these studies, microorganisms were entrapped in polymeric materials (e.g., polyacrylamide or silica) or inorganic spheres that were orders of magnitude larger than thin films (see pg. 14201, col. 1, para. 2 to col. 2, para. 1). Liu teaches that the ability to make nanofibers and microfibers from water-soluble polymers by electrospinning offers a way to create hydrogels with nano- and microstructures (see pg. 14201, col. 2, para. 3). Liu teaches that a problem to be solved when encapsulating microbes in polymer fibers by co-electrospinning is that the porosity of the outer layers of the fiber must be increased to facilitate the transfer of material between the microbe and its environment (see pg. 14201, col. 2, para. 2). The fibers fabricated in Liu’s study formed a uniform, cross-linked scaffold with a 3D porous structure (see pg. 14202, col. 2, para. 3), and the mesh-like network of the polymer effectively immobilized the microbes while allowing the exchange of nutrients and metabolic products between the microorganism and the environment (see pg. 14205, col. 2, para. 1). Liu teaches that during electrospinning, the fibers overlap each other in a completely random manner, giving rise to the open pore structure ideal for use as membranes and in filtration (see pg. 14202, col. 1, para. 1).
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Lidstrom and Liu, because Liu teaches bacteria can be contained and immobilized in the microfibers of a hydrogel to facilitate the transfer of material between the microbe and its environment. One would have been motivated to do so, because Liu’s system immobilizes the microbes while advantageously maintaining their metabolic activity and their exposure to the environment which can be useful for filtration and in bioremediation. One would have recognized that the polymeric hydrogel of Liu serves the same purpose as the solid supports of Lidstrom who teaches the supports may comprise a polymer. Hence, one would have recognized the results of using the hydrogel taught by Liu to immobilize the bacteria in the biofilter taught by Lidstrom would have been predictable. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 4, Liu teaches the hydrogel to be an efficient support material (pg. 14201, col. 2, para. 3) containing cross-linked microfibers that form a mesh-like network (see pg. 14205, col. 1, para. 2), which meets the limitation of “wherein the plurality of…microfibers…are contained in or fabricated as…meshes”.
Regarding claim 5, Lidstrom teaches the methanotrophs of the disclosure are well suited for developing a modular system (see pg. 8, para. [0092]), and teaches that the filter units comprising the bacteria can be replaced once they are no longer functional (see pg. 12, para. [0133) and can be placed in a pipe or chamber through which methane is passed from the gaseous substrate (see pg. 12, para. [0132]). In view of the instant specification, the instantly claimed “modular units” are characterized in that they can be inserted into a superstructure or device (see pg. 3, para. 29-30) and can be easily replaced (see pg. 8, lines 17-18). Lidstrom also teaches the filter is a mesh that comprises a size that is large enough to permit passage of the gaseous substrate but not too large that the bacteria will pass through (see pg. 12, para. [0133]). Hence, the filter unit taught by Lidstrom meets the limitation of a “modular unit”, and it would have been obvious to have fabricated the “meshes” into a modular unit as described by Lidstrom.
Regarding claim 15, Lidstrom teaches the methanotroph may include Methylomicrobium alcaliphilum 20Z (see pg. 3, para. [0057]). In view of Orata et al., Methylomicrobium alcaliphilum is the same species as Methylotuvimicrobium alcaliphilum (see Abstract).
Regarding claim 16, Lidstrom teaches the methanotroph may include Methylomicrobium buryatense 5G (see pg. 3, para. [0041]). In view of Orata et al., Methylomicrobium buryatense is the same species as Methylotuvimicrobium buryatense (see Abstract).
Regarding claim 17, Lidstrom teaches the bacteria to comprise halophilic methanotrophs, which include Methylomicrobium alcaliphilum 20Z (see pg. 8, para. [0092]). In view of Orata et al., Methylomicrobium alcaliphilum is the same species as Methylotuvimicrobium alcaliphilum (see Abstract).
Regarding claim 18, Lidstrom teaches that human-related activities, such as fossil fuel production (e.g., oil and gas production), are major contributors to global CH4 emissions (see pg. 1, para. [0004]), and the CH4 for the invention can be obtained from natural gas or fracking facilities (see pg. 9, para. [0110]). Hence, it would have been obvious to have attached the product of manufacture to a natural gas processing plant or an oil well.
Regarding claim 25, the further limitation of “wherein the media comprising a rare earth element comprises lanthanum” refers to a product-by-process step which does not limit the structure of the claimed product, as discussed regarding claim 1. Hence, the claim is obvious for the same reasons as claim 1.
Regarding claim 26, the further limitation of “wherein the media further comprises calcium, copper or tungsten” refers to a product-by-process step which does not limit the structure of the claimed product, as discussed regarding claim 1. Hence, the claim is obvious for the same reasons as claim 1.
Regarding claim 27, Lidstrom teaches the methanotroph may include Methylomicrobium alcaliphilum 20Z (see pg. 3, para. [0057]).
Regarding claim 28, Lidstrom teaches that the source of gaseous methane fermented by the bacteria can be obtained from landfill emissions (see pg. 9, para. [0110]). Hence, it would have been obvious to have contained the product of manufacture in a landfill.
Regarding claim 30, Liu teaches the hydrogel to be an efficient support material (pg. 14201, col. 2, para. 3) containing cross-linked microfibers that form a mesh-like network (see pg. 14205, col. 1, para. 2), which meets the limitation of “wherein the plurality of…microfibers…are contained in or fabricated as…meshes”.
Regarding claim 31, Lidstrom teaches that human-related activities, such as fossil fuel production (e.g., oil and gas production), are major contributors to global CH4 emissions (see pg. 1, para. [0004]), and the CH4 for the invention can be obtained from natural gas or fracking facilities (see pg. 9, para. [0110]). Hence, it would have been obvious to have attached the product of manufacture to a natural gas processing plant or an oil well.
Regarding claim 32, the claim according to limitation “(i)” is obvious in view Lidstrom and Liu for the same reasons discussed regarding claim 1.
Regarding claim 33, Lidstrom teaches the methanotroph may include Methylomicrobium alcaliphilum 20Z (see pg. 3, para. [0057]).
Claim(s) 19-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lidstrom and Liu as applied to claims 1, 4-5, 15-18, 25-28 and 30-33 above, and further in view of Thoniyot et al. (previously cited), hereafter, “Thoniyot”.
Regarding claim 19, Lidstrom teaches a methane fermentation bioreactor, comprising a plurality of polymers attached to immobilized, viable halophilic methanotrophic bacteria that function by removing gaseous methane from a gaseous substrate, as discussed above.
Liu teaches the immobilization of viable, metabolically active microbes acting as catalytic centers for environmental remediation using nanofibers and microfibers from polymers to create hydrogels with nano- and microstructures to facilitate the transfer of material between the microbe and its environment, as discussed above.
Thoniyot teaches that the structural combination of a polymer hydrogel network with a nanoparticle (metal or metal oxide) holds the promise of providing superior functionality to the composite material with applications in diverse fields, including catalysis and environmental remediation, and this mixing may result in synergistic property enhancement, such as increased mechanical strength and stimuli response (see Abstract; pg. 1, col. 2, para. 1). Thoniyot teaches that recently reported silica (silicon oxide) nanoparticles demonstrated remarkable improvements in mechanical stiffness and bioactivity compared to hydrogel without nanoparticles (see pg. 1, col. 2, para. 1). Thoniyot teaches that in one of the earliest investigations of such materials, gold nanoparticles were immobilized in polyacrylamide, resulting in uniform distribution of the gold nanoparticles in the gel matrix (see pg. 1, col. 2, para. 2). In another study, researchers prepared gold nanoparticle hydrogels by adding nanoshell gold nanoparticles into a solution of monomers (see pg. 2, col. 2, para. 2). Thoniyot teaches that hydrogels infused with noble metal nanoparticles (such as gold) showed excellent retention of catalytic activity because aggregation induced deactivation was prevented by the hydrogel network (see pg. 9, col. 1, para. 1). Thoniyot teaches that nanoparticle-hydrogel composites exhibit multi-functional and stimuli responsive properties, making them ideal for environmental remediation systems for catalytic oxidation of toxins and the removal of pollutants (see pg. 11, col. 2, para. 1).
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Lidstrom, Liu and Thoniyot for at least the following reasons. First, one would have recognized the advantages of immobilizing the microbes taught by Lidstrom using a hydrogel taught by Liu, because Liu teaches that doing so maintains the bacteria’s metabolic activity and their exposure to the environment which can be useful for filtration and in bioremediation. Further, one would have recognized from Thoniyot that the use of metal oxide nanoshells or non-metal oxide (e.g., silica) nanoshells in hydrogels is known in the art, and Thoniyot teaches such hydrogels have increased mechanical strength, retain catalytic activity, and are ideal for the environmental removal of pollutants. One would have recognized from Lidstrom and Liu that this retention of catalytic activity by the bacteria is an important factor when immobilizing them in a polymeric material for the bioprocessing of a substrate (i.e., methane). Hence, one would have recognized there to be an advantage when using a plurality of metal oxide nanoshells in the hydrogel and there to be a reasonable expectation of success when applying the combination. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 20, Thoniyot teaches metal nanoshells, as discussed above.
Regarding claim 21, Thoniyot teaches the metal nanoshells are gold nanoshells, as discussed above.
Regarding claim 22, Thoniyot also teaches nanoparticle-based hydrogels comprising cadmium selenide (CdSe) or cadmium telluride (CdTe) which were able to form stable gels even under irradiation by visible light (see pg. 5, col. 2, para. 2). Thoniyot teaches that polymeric nanoparticles composed of “core-shell” particles have been developed for a variety of applications, and the inclusion of these particles in a hydrogel results in enhanced biological stability and mechanical properties (see pg. 10, col. 2, para. 2). Thoniyot teaches hydrogels wherein core-shell particles comprising a CdSe core are coated in a CdS shell (CdSe/CdS core-shell nanoparticle) and incorporated into a hydrogel (see pg. 10, col. 1, para. 1). Hence, it would have been obvious for the plurality of nanoshells to comprise CdSe nanoparticles coated with CdS.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lidstrom, as applied to claims 1, 15-17, 25-27 and 32-33 above, and further in view of Nagpal et al., US 2022/0235384 A1 (effectively filed 05/14/2019; previously cited), hereafter, “Nagpal”, and McElroy et al. (previously cited), hereafter, “McElroy”.
Regarding claim 23, Lidstrom teaches a methane fermentation bioreactor, comprising a plurality of polymers attached to immobilized, viable halophilic methanotrophic bacteria that function by removing gaseous methane from a gaseous substrate. Lidstrom also teaches the gaseous substrate for fermentation by the methanotrophic bacteria may also include carbon dioxide (see pg. 3, para. [0056]). Lidstrom also discusses the production of useful products from the gaseous substrate (see, e.g., pg. 2, para. [0033]; pg. 3, para. [0054]; pg. 7, para. [0090]).
Lidstrom does not teach wherein the plurality of methane-capturing bioagents are (i) attached to or contained in a plurality of nanoparticles, wherein the plurality of nanoparticles comprise CdTe nanoparticles coated with CdSe.
Nagpal teaches nano-biohybrid organisms (e.g., bacteria) comprising different core-shell quantum dots (QDs) or gold nanoparticle clusters, which, when illuminated by light, drive the renewable production of biofuel molecules and chemicals using carbon-dioxide (CO2) as a substrate (see pg. 1, para. [0002]). Nagpal teaches that many naturally occurring and synthetic bacteria can accomplish industrially relevant reactions using chemical energy to generate electrons and reduce readily available chemical feedstocks and can be labeled as living factories. However, they derive the chemical energy needed sometimes from valuable food stocks, thereby reducing their attraction for energy conversion to useful solar or biofuels. Inorganic photocatalysts directly derive energy from sunlight to generate photoelectrons for reduction of inexpensive and abundant chemical feedstocks like, for example, air, water, and carbon-dioxide, but their lack of selectivity, low efficiency, and sometimes use of conditions such as high-temperature and pressure limit their widespread application. See pg. 36, para. [0388].
Nagpal teaches that combining these desired functionalities of direct stimuli-activations via light, voltage, or magnetic field, with the versatility of designing desired synthetic metabolic networks in living cells can provide an unprecedented platform for designing and creating multifunctional living nano-biohybrid organisms (or nanorg's), and for specific applications as living solar-powered factories for direct energy conversion to solar fuels. See pg. 37, para. [0389].
Nagpal teaches that living nano-biohybrid organisms or nanorgs combine the specificity and well-designed surface chemistry of an enzyme catalyst site, with the strong light absorption and efficient charge injection (for biocatalytic reaction) from inorganic materials, and metal nanoparticles and nanoclusters (NCs), such as gold (Au), offer strong light absorption properties and biocompatibility for potential application in living nanorgs (see pg. 38, para. [0396]). Nagpal teaches that biochemical conversion of inexpensive feedstocks like, such as air, water, and carbon dioxide, offers specificity and low cost (see pg. 38, para. [0397]). Nagpal teaches that living or whole-cell biohybrids offer additional advantage of self-replication or growth, avoiding enzyme deactivation, and enzyme generation and repair (see pg. 38, para. [0398]).
Nagpal teaches embodiments wherein the nano-biohybrid bacteria comprise a core-shell quantum dot, wherein said core is selected from CdS or CdSe, and coated with a ZnS shell (see pg. 1, para. [0009]; pg. 8, para. [0060]). As illustrated in FIG. 1A, the quantum dots absorb sunlight in non-photosynthetic bacteria for direct solar-to-chemical fuel production using air, water and CO2 as chemical feedstocks (see pg. 8, para. [0057]).
Nagpal does not teach the nanoshells comprising CdTe nanoparticles coated with CdSe.
McElroy teaches the synthesis and characterization of CdTe/CdSe core/shell colloidal quantum dots, having an absorption edge in the near-infrared, potentially enabling more efficient exploitation of the solar spectrum (see Abstract). McElroy teaches that there are a number of properties of the QDs that make them well-suited to the role of photo absorbers, as they are photo-stable and highly absorbing (see pg. 65, col. 1, para. 1). It was also apparent that the samples with CdTe-cores outperformed their CdSe analogues (see pg. 70, col. 1, para. 1).
It would have been obvious at the time of filing for a person of ordinary skill to have arrived at the claimed invention by combining the teachings of Lidstrom, Nagpal and McElroy, because both Lidstrom and Nagpal teach the use of bacteria as effective reducers of carbon emissions, such as gaseous methane and carbon dioxide, and Nagpal further teaches the use of bacteria as solar-powered fuel factories to produce useful products from carbon dioxide. As Nagpal and McElroy teach various core/shell nanoparticles (e.g., CdSe/CdTe, CdTe/CdSe, CdSe/CdTe/CdS, CdS/ZnS, CdSe/ZnS, etc.) sharing similar functional properties, one would have recognized each to be a potential alternative to using the core-shell quantum dots (nanoshells) taught by Nagpal. Furthermore, one would have been particularly motivated to have used the CdTe/CdSe nanoshells taught by McElroy to increase the light absorption of the system, which would have been expected to enhance carbon dioxide reduction and increase the production of useful products. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lidstrom and Nagpal, as applied above, and further in view of Rosenman et al. (US Patent No. 9,991,458 B2; previously cited), hereafter, “Rosenman”.
Regarding claim 24, Lidstrom teaches the fermentation of gaseous methane and carbon dioxide by immobilized methanotrophic bacteria and the production of useful products from the gaseous substrates, as discussed above. Nagpal teaches nano-biohybrid bacteria comprising a core-shell quantum dot, which absorbs sunlight for direct solar-to-chemical fuel production using air, water and CO2 as chemical feedstocks using non-photosynthetic bacteria, as discussed above. Nagpal also teaches that metal nanoparticles and nanoclusters (NCs), such as gold (Au), offer strong light absorption properties and biocompatibility for the microorganisms to function as living solar-powered factories for direct energy conversion to solar fuels, as discussed above.
Lidstrom and Nagpal do not teach wherein the plurality of gold nanoshells comprise a silica core coated by a gold metallic shell.
Rosenman’s disclosure relates to methods of fabricating a nanoshell (see col. 1, lines 57-59). Rosenman teaches these small particles enable construction of materials and structures of well-defined properties, enabling opportunities for technological and commercial development in applications such as biotechnology (see col. 1, lines 26-34). Rosenman teaches that metallic nanoshells effectively interact with light due to collective oscillations of the conduction electrons on the surface of the nanoshell, and the composition of the nanoshell can advantageously result in the higher absorption of light and spectral sensitivity (see col. 16, lines 47-58). Rosenman teaches this effect may be much stronger if the metal nanoparticles have a core-shell structure, for example, a metal coating on a spherical core, where gold shells are formed on silica particles (see col. 17, lines 46-55). Roseman teaches the “silica core-gold nanoshells” (see col. 17, lines 56-57), comprising a silica core, are coated with gold (Au) (see col. 13, lines 52-55).
It would have been obvious at the time of filing for a person of ordinary skill to have arrived at the claimed invention by combining the teachings of Lidstrom, Nagpal and Rosenman, because both Lidstrom and Nagpal teach the use of bacteria as effective reducers of carbon emissions, such as gaseous methane and carbon dioxide, and Nagpal further teaches the use of bacteria as solar-powered fuel factories to produce useful products from carbon dioxide. As Rosenman teaches metallic nanoshells, such as silica core-gold nanoshells, effectively increase light absorption and spectral sensitivity, one would have been motivated to have used the silica core-gold nanoshells taught by Rosenman to increase the light absorption of the system, which would have been expected to enhance carbon dioxide reduction and increase the production of useful products. Furthermore, there would have been a reasonable expectation of success, because Nagpal teaches that metal nanoparticles and nanoclusters (NCs), such as gold (Au), offer strong light absorption properties and are biocompatible with microorganisms. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Response to Arguments
Regarding the Claim Interpretation set forth in the previous Office Action, Applicant argues that as set forth in Akberdin, et al (2018) Frontier in Microbial, vol 9, pgs 1 to 12, exposure of Methylomicrobium cells to RREs in fact does change the structure, or phenotype, of the cells in that a methanol dehydrogenase is transcriptionally repressed, and a lanthanum-dependent methanol dehydrogenase is activated. Thus, the composition - or structure - of RRE-exposed Methylomicrobium cells is changed, i.e., exposing Methylomicrobium cells to RRE results in a phenotype alteration in the Methylomicrobium cells comprising alterations in transcription of methanol dehydrogenases, thus RRE exposure resulting in different amounts of methanol dehydrogenases in the cells before and after the RRE exposure, thus causing a redox balance alteration in the cells. Accordingly, data demonstrates that Methylomicrobium cells exposed to RRE are structurally altered,
this structural alteration (inter alia, different amounts of methanol dehydrogenases in the cells before and after the RRE exposure) resulting in a redox balance alteration in the cells.
Applicant’s arguments have been fully considered but they are not persuasive.
Applicant’s argument assumes that the change in the observed function (phenotype) of the bacteria necessitates a change in structure, but Applicant’s argument fails to identify or provide objective evidence for any change in structure. Even in view of Akberdin, the examiner has not found any evidence of any change in any structure of the bacterium, only the transcriptional repression and activation of certain preexisting metabolic pathways expressing methanol dehydrogenase (MeDH) enzymes (see Akberdin at “Background”). Akberdin also states:
Cells exposed to REEs display higher rates of growth but have lower carbon conversion efficiency compared to cells supplemented with Ca. The most plausible explanation for these physiological changes is an increased conversion of methanol into formate by XoxF-MeDH, which further stimulates methane oxidation but limits both the supply of reducing power and flux of formaldehyde into the RuMP pathway. (See pg. 2, “Conclusion”)
It is clear from Akberdin that these changes in metabolism result in the increase and decrease of certain activities, e.g., methane consumption, as shown in Table 1, and these metabolic changes are an inherent property of Methylomicrobium in response to REE exposure. These effects are due to the bacteria’s ability to regulate pre-existing metabolic pathways, and are not evidence of any change in the bacteria’s structure. These effects are transient, not permanent, and the genetic structure which underlies the metabolic pathways involved is present regardless of their level of expression.
Furthermore, the only structure Applicant has identified in their argument are “different amounts of methanol dehydrogenases”. These enzymes are not properly considered to be a structure of the bacteria themselves, but rather are products that are produced by said bacteria.
It is also apparent in view of Akberdin that this genus of bacteria are already known to produce these enzymes, and exposure to REEs merely changes the amounts of different sub-types that are produced in culture.
Applicant further argues that Dr. Kalyuzhnaya’s expert declaration dated March, 30, 2026, should also be considered, which declares that exposing a halophilic methanotroph cell to an RRE triggers a "genetic switch" between two different types of methanol dehydrogenase enzymes, i.e., one of skill in the art after reading Dr. Kalyuzhnaya's expert declaration and the art cited in that declaration would understand that exposing a halophilic methanotroph cell to an RRE triggers a “structural change” in the halophilic methanotroph cell in that the RRE exposure alters enzyme composition in the halophilic methanotroph cell - thus the pre-RRE exposure cell is structurally different from the post-RRE exposed cell.
Applicant’s arguments have been fully considered but they are not persuasive.
The opinions presented in the declaration signed by the co-inventor of the present invention above was fully addressed in the previous Office Action. The opinions set forth in this declaration failed to present any distinctive “structural change” in the bacterium as being a result of the product-by-process step of culturing. Therefore, there was no resulting change in structure for the examiner to consider as amounting to a patentable difference. The examiner disagrees with Applicant’s remarks alleging that the changes in gene expression should be regarded as changes in structure, for the same reasons discussed above.
Applicant further argues that one of skill in the art after reading Dr. Kalyuzhnaya's expert declaration and the art cited in that declaration would understand that exposing a halophilic methanotroph cell to an RRE results in a higher growth rate, and one of skill would also understand that a cell having a higher growth rate than a comparable cell would necessarily have a different structural (phenotypic) composition in that growth enzymes or structures would be expressed in the faster growing cells as compared to the slower growing cells.
Applicant’s arguments have been fully considered but they are not persuasive.
Applicant appears to be arguing that “a higher growth rate” should be regarded as a change in structure, but this is not a tenable argument. The “growth rate” of a bacterium is clearly a function, not a structure. Furthermore, the expression of any enzymes in the faster growing cells is not considered to be a structural difference in the bacterium for the same reasons discussed above.
Applicant further argues that one of skill in the art after reading Dr. Kalyuzhnaya's expert declaration and the art cited in that declaration would understand that exposing a halophilic methanotroph cell to an RRE results in the cell being "less efficient" and thus that cell would have less biomass (less biomass to satisfy the altered redox requirements), thus, biomass composition (e.g., amount) is altered in the RRE exposed halophilic methanotroph cell - thus the pre-RRE exposure cell is structurally different from the post-RRE exposed cell.
Applicant’s arguments have been fully considered but they are not persuasive.
A change in biomass due to the upregulating/downregulating of preexisting metabolic pathways is a functional response to changes in the bacteria’s environment or culture conditions. These effects are directed to a transient, functional change, rather than a permanent, structural change, and the metabolic pathways involved are present regardless of the bacteria’s “efficiency” under said conditions.
Applicant further argues that one of skill in the art after reading Dr. Kalyuzhnaya's expert declaration and the art cited in that declaration would understand that exposing a halophilic methanotroph cell to an RRE results in an increase in TCA cycle intermediates and a decrease in RuMP pathway intermediates, thus creating a structural (phenotypic) difference between pre-RRE exposed cells and post-RRE exposed cells.
Applicant’s arguments have been fully considered but they are not persuasive.
Increasing or decreasing “intermediates” in a metabolic pathway naturally correlates to the upregulation and downregulation of gene expression in said pathway, which is a functional response to changes in the bacteria’s environment or culture conditions. These effects are directed to a transient, functional change, rather than a permanent, structural change, and the metabolic pathways involved are present regardless of the levels of intermediates being produced at a given time.
Regarding the rejections under 35 U.S.C. 102(a)(1), Applicant argues that Lidstrom is defective in that it does not teach the use of halophilic methanotroph bacterial cells (for example, Methylomicrobium) that have been structurally altered after exposure to RREs, as discussed above. The instant amendment also addresses this issue by clarifying that
methanotroph bacterial cells (for example, Methylomicrobium) are structurally altered as a result of their exposure to RREs, as discussed above. Orata does not teach use of halophilic methanotroph bacterial cells (for example, Methylomicrobium) that have been structurally altered after exposure to RREs, and thus does not cure the defect in Lidstrom.
Applicant’s arguments have been fully considered but they are not persuasive.
Applicant’s argument fails to identify any change in structure of the bacterium itself that is implied by the product-by-process step of exposing the bacteria to REEs. Furthermore, as discussed under Claim Interpretation and 35 U.S.C. 112(b), the amendments to the claims have not changed the examiner’s interpretation, because they merely rephrase the same limitations that were recited in the previous claim set. As discussed in the present rejection, patentability of a product is determined by the structure of the product itself, not by its method of production, and the product-by-process limitation of the claim does not result in a structural difference in the claimed product. See also the Response to Arguments regarding Claim Interpretation above.
Regarding the rejections under 35 U.S.C. 103, because Liu does not teach or suggest exposing halophilic methanotroph bacterial cells to RREs, one of skill in the art after reading Liu and Orata would not have been motivated to modify Lidstrom to teach this claimed invention. Accordingly, because inter alia neither Lidstrom in view of Orata nor Liu alone or in combination teach or suggest the claimed invention, and because inter alia one of skill in the art after reading Liu at the time of the invention would not have been motivated to modify Lidstrom to make this claimed invention, this rejection under section §103, can be properly withdrawn.
Applicant’s arguments have been fully considered but they are not persuasive.
Applicant’s argument regarding the product-by-process step of “exposing halophilic methanotroph bacterial cells to RREs”, has been fully addressed above, as it relates to the present rejections under 35 U.S.C. 103.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Liu teaches bacteria can be contained and immobilized in the microfibers of a hydrogel to facilitate the transfer of material between the microbe and its environment, as discussed in the rejection. One would have been motivated to combine these teachings, because Liu’s system immobilizes the microbes while advantageously maintaining their metabolic activity and their exposure to the environment which can be useful for filtration and in bioremediation, as discussed in the rejection. Applicant’s argument fails to specifically address any alleged deficiency in this rationale.
Applicant argues that one of skill in the art at the time of this invention after reading Thoniyot, cited only for teaching inter alia polymer hydrogel networks and gold nanoshell particles, would not have been motivated to modify Lidstrom and Liu to make this claimed invention. Accordingly, because inter alia neither Lidstrom nor Liu or Thoniyot alone or in any combination teach or suggest this claimed invention, this rejection under section §103, can be properly withdrawn.
Applicant’s arguments have been fully considered but they are not persuasive.
As discussed in the rejection, one would have recognized from Thoniyot that the use of metal oxide nanoshells or non-metal oxide (e.g., silica) nanoshells in hydrogels is known in the art, and Thoniyot teaches such hydrogels have increased mechanical strength, retain catalytic activity, and are ideal for the environmental removal of pollutants. One would have recognized from Lidstrom and Liu that this retention of catalytic activity by the bacteria is an important factor when immobilizing them in a polymeric material for the bioprocessing of a substrate (i.e., methane). Applicant’s argument fails to specifically address any alleged deficiency in this rationale.
Applicant further argues that one of skill in the art at the time of this invention after reading Napal and McElroy would not have been motivated to modify Lidstrom to make this claimed invention. Accordingly, because inter alia neither Lidstrom nor Napal or McElroy alone or in any combination teach or suggest this claimed invention, this rejection under section §103, can be properly withdrawn.
Applicant’s arguments have been fully considered but they are not persuasive.
As discussed in the rejection, one would have been particularly motivated to have used the CdTe/CdSe nanoshells taught by McElroy to increase the light absorption of the system, which would have been expected to enhance carbon dioxide reduction and increase the production of useful products. Applicant’s argument fails to specifically address any alleged deficiency in this rationale.
Applicant further argues that one of skill in the art at the time of this invention after reading Rosenman would not have been motivated to modify either Lidstrom and/or Nagpal to make this claimed invention. Accordingly, because inter alia neither Lidstrom nor Napal or Rosenman alone or in any combination teach or suggest this claimed invention, this rejection under section §103, can be properly withdrawn.
Applicant’s arguments have been fully considered but they are not persuasive.
As discussed in the rejection, one would have been motivated to have used the silica core-gold nanoshells taught by Rosenman to increase the light absorption of the system, which would have been expected to enhance carbon dioxide reduction and increase the production of useful products. Applicant’s argument fails to specifically address any alleged deficiency in this rationale.
Conclusion
No claims 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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/DENNIS IGNATIUS ARMATO JR/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
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