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 .
Claim Status
The amendment on April 27, 2026 is acknowledged. Claims 1-59 are currently pending. Claims 47-59 have been withdrawn. There are no new or canceled claims. Claims 1-46 will be examined on the merits herein.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-46 in reply filed on April 27, 2026 is acknowledged. Claims 47-59 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
The application 18/380,447 filed on October 16, 2023 claims priority from the PROVISIONAL filed on October 14, 2022.
Information Disclosure Statement (IDS)
At the time of the instant Office Action, no IDS had been received. Applicant is reminded of their duty to disclose (see CFR 1.56).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 7-11, 15-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chiang et al. (Published 2021; hereafter Chiang; PTO-892).
As claims 1-2, 7-11, 15, Chiang teaches an efficient, cloning-free strategy for the cluster refactoring and total biosynthesis of fungal natural products (NPs) in Aspergillus nidulans.
Chiang teaches the platform places genes of interest (GOIs) under the regulation of the robust asperfuranone afo biosynthesis gene machinery, allowing for their concerted activation upon induction.
Chiang teaches the utility of the system by creating strains that can synthesize high-value NPs, citreoviridin (1), mutilin (2), and pleuromutilin (3), with good to high yield and purity. This platform can be used not only for producing NPs of interests (i.e., total biosynthesis) but also for elucidating cryptic biosynthesis pathways.
Chiang teaches that native promoters of highly expressed Biosynthetic Gene Clusters (BGCs) can be leveraged to achieve high yields of heterologously expressed secondary metabolites (SMs).
Chiang teaches Aspergillus nidulans is a filamentous fungus that has been popularly used as heterologous chassis. As a model organism, it has well-established genetic tools such as complementation markers and efficient gene targeting.
Chiang teaches Aspergillus nidulans, mutilin producing stains (YM283 – YM287; YM346 and 350), citreoviridin producing strains (YM186 - YM195). See for example, table 1 (Supporting info) below.
Chiang teaches a strain that can produce mutilin, a key intermediate in the pleuromutilin biosynthetic pathway. See for example, Figure 5a.
Chiang teaches successfully reconstituted the citrinin (19.1 mg/L) and pleuromutilin (84.2 mg/L) biosynthetic pathways from the cDNA of native strains in Aspergillus orzae.
Chiang teaches that large DNA fragments can be assembled in vivo with high efficiency and that a 4-gene citreoviridin biosynthesis pathway can be reconstituted and refactored in the afo regulon in one transformation to give strains with high production yield and high purity.
Chiang teaches five pl genes (pl-ggs, pl-cyc, pl-p450-1, plp450-2, and pl-sdr) were amplified from the cDNA of Clitopilus passeckerianus and assembled with intergenic regions of the afo regulon. See for example, Supporting information; table 1.
Chiang teaches exchanging the coding regions of AN1030–AN1036 with seven heterologous genes (Pl-ggs, cyc, atf, sdr, p450-1, p450-2, and p450-3) of the basidiomycete fungi Clitopilus passeckerianus. See for example table 1 (Supporting info) below.
Chiang teaches popularly used as heterologous chassis and the reconstitution of the 6-gene, asperfuranone (3.8 mg/L) and 4-gene citreoviridin (∼10.5 mg/L) biosynthetic pathways in a defined integration site via homologous recombination (HR) utilizing an A. nidulans strain deficient in nonhomologous end joining (nKuAΔ). The genes were all under the control of strong inducible alcohol
dehydrogenase promoter (PalcA).
Chaing teaches that, Frandsen et al. reconstituted the 4-gene carminic acid pathway in defined integration sites under the control of the constitutive gpdA promoter.
As claims 16-18, Chiang teaches the genomic sequence of the afo locus in the strain YM81, and the intergenic region between AN1037 and AN1036 (also known as afoG) (named 1036P), intergenic region between AN1036 and AN1035 (also known as afoF) (named 1036T, 1768 bp), intergenic region between AN1035 and AN1034 (also known as afoE) (named 1035P, 527 bp), intergenic region between AN1034 and AN1033 (also known as afoD) (named 1034P, 849 bp), intergenic region between AN1033 and AN1032 (also known as afoC) (named 1033P, 605 bp), intergenic region between AN1031 and AN1030 (named 1031T, 591 bp), intergenic region between AN1030 and PalcA-AN1029 (also known as afoA) (named 1029P, 1221 bp)*. See for example, Supplemental information; Table 3.
Chiang also teaches a complete BGC refactoring strategy and heterologous expression platform in Aspergillus nidulans based on the afo regulon. Chiang teaches that in a previous study, the induction of AfoA, the pathway-specific transcription activator, led to the concerted expression of all the afo genes and the robust production of asperfuranone and its intermediate (∼900 mg/L).
Chiang does teach that “taking advantage of the transcriptional regulatory elements of afo, we replaced the afo genes with Genes of Interest (GOIs) from a target BGC”.
Chiang also teaches “the induction of afoA would thus result in the specific activation of our refactored BGC and production of the encoded molecule, which, we hypothesized, would be in similar abundance as asperfuranone and its intermediate. The strategy is cloning-free and generates compound-producing strains rapidly. The host is easily amendable to subsequent titer optimization or genetic dereplication”.
Chiang teaches that the platform was applied to two high-value Natural Products clusters and successfully obtained high-yielding strains.
Chiang teaches the biosynthesis of asperfuranone in A. nidulans. (a) Gene organization of the afo regulon in chromosome VIII. AN1029 (afoA) is the positive regulator of the afo regulon. All afo genes are
transcribed by their own promoters, which are under the control of AfoA. The insertion of the inducible alcA promoter (PalcA) into the 5’region of afoA generated the strain YM47. Induction of PalcA drives the expression of AfoA, which then activates the afo cluster (AN1036−AN1030, same as AfoGFEDCB), leading to the production of asperfuranone. See for example, Figure 2. See Figure 2 below; See Supplemental Figure 1, Table 1.
Chiang teaches YM186 – YM195 strains: pyrG89; pyroA4; nkuA::argB; riboB2; stcA-stcWΔ; AN1029::PalcA-AN1029; AN1036-AN1032::ctvA-ctvB-ctvC-ctvD-AfpyrG. See for example, Supplemental Figure 1, Table 1.
Chiang teaches YM283 – YM287 strains: pyrG89; pyroA4; nkuA::argB; riboB2; stcA-stcWΔ; AN1029::PalcA-AN1029; AN1036-AN1031Δ::pl_ggs-cyc-p450_1-p450_2-sdr-AfpyroA. See for example, Supplemental Figure 1, Table 1.
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Regarding the limitation "for upgrading intermediate oxidation products formed by catalytic degradation of linear and/or branched alkanes, polystyrenes, or mixtures thereof," the claim teaches all structural features from the claim, so it is presumed to be capable of the claimed intended use. See MPEP 2112.01: "Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433." See also MPEP 2111.02: "To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997)"
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 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Chiang et al. (Published 2021; hereafter Chiang; PTO-892) as applied to claims 1-2, 7-11, 15 in view of Ru et al. (Published April 21, 2020; hereafter Ru; PTO-892).
Chiang teaches all the limitations of claim 1-2, 7-11, 15 as fully disclosed above and incorporated herein.
However, Chiang does not teach the linear and/or branched alkanes are polyethylenes or polypropylenes, or mixtures thereof, as claim 3.
Chiang also does not teach polypropylenes, or mixtures thereof or the linear and/or branched alkanes are provided as new or used motor oil-based materials, as claim 4.
Ru teaches the microorganisms and enzymes that are able to degrade a variety of generally used synthetic plastics, such as polyethylene (PE), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), polyurethane (PUR), and polyethylene terephthalate (PET), which is pertinent to claims 3-4. See for example, Tables 2-7.
Ru also teaches the microbial metabolic pathways for plastic depolymerization products and the current attempts toward utilization of such products as feedstocks for microbial production of chemicals with high value, which is pertinent to claim 3-4.
Ru teaches the initial step of the microbial degradation process is to secrete depolymerases to break down the long-chain polymers into low molecular weight oligomers or monomers, which can be further assimilated into microbial cells or metabolized into CO2, which is pertinent to claims 3-4.
Ru teaches bio-upcycling plastic wastes by connecting the biodegradation of plastic wastes to the biosynthesis of valuable chemicals in microorganisms, which is pertinent to claim 3-4.
Ru teaches Aspergillus niger, Aspergillus sydowi, Aspergillus flavus, Aspergillus tubingenesis, Aspergillus sp. S45, which is pertinent to claims 3-4.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Chiang and Ru by connecting the biodegradation of plastic wastes to the biosynthesis of valuable chemicals in microorganisms, such as mutilin and citreoviridin, thereby arriving at the invention of claims 3, 4. Since the complete BGC refactoring strategy and heterologous expression platform in Aspergillus nidulans based on the afo regulon taught by Chiang and the synthetic plastics of Ru, such as polypropylene and polyethylene terephthalate can be used as feedstocks for microbial production of chemicals with high value, including Aspergillus, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over rejected under 35 U.S.C. 103 as being unpatentable over Chiang et al. (Published 2021; hereafter Chiang; PTO-892) as applied to claims 1-2, 7-11, 15 above in view of Ru et al. (Published April 21, 2020; hereafter Ru; PTO-892), and further view of Sheridan (Published October 17, 2016; hereafter Sheridan; PTO-892).
Chiang teaches all the limitations of claim 1-2, 7-11, 15 as fully disclosed above and incorporated herein.
However, neither Chiang or Ru teach ergothioneine (EGT) as claim 5.
Sheridan teaches the identification of a key EGT biosynthetic gene in A. fumigatus and reveal new insights into systems biology of EGT biosynthesis and functionality in fungi, which is pertinent to claim 5.
Sheridan teaches the proteomic remodeling A. fumigatus undergoes when EGT biosynthesis is impeded and the mutant is forced to deal with oxidative stress, which is pertinent to claim 5.
Sheridan teaches metabolic pathways linking cystathionine, glutathione and methionine metabolism, comparison of Δ egtA26933 and ATCC26933 under basal conditions showing an absence of cystathionineγ-synthase, which converts cysteine to cystathionine. This could be due to a switch towards increased glutathione production. Comparison of Δ egtA26933 and ATCC26933 upon addition of 3 mM H2O2 shows an increased abundance of cystathionine β-synthase, which converts cystathionine to homocysteine. This would result in increased production of SAM, which is required for EGT biosynthesis, which is pertinent to claim 5. See for example Fig. 5.
Sheridan teaches ergothioneine biosynthesis in Aspergillus fumigatus, afu2g_15650 and Afu2g_13295, which is pertinent to claim 5.
Sheridan teaches a minimal amount of EGT was still found in the Egt2 deletion strain, explained by a spontaneous conversion of hercynylcysteine sulphoxide to EGT by an unrelated PLP-binding enzyme, which is pertinent to claim 5.
Sheridan teaches “H2O2 addition to Δ egtA26933 resulted in increased abundance of imidazole glycerol phosphate synthase subunit HisF (AFUA_ 2G06230) of log2 1.11-fold compared to ATCC26933 under the same conditions. HisF is involved in histidine biosynthesis catalyzing the closure of the imidazole ring. The observation of an increased abundance of imidazole glycerol phosphate synthase subunit HisF in Δ egtA26933 compared to wild-type under oxidative stress suggests that histidine production is increased when A. fumigatus is exposed to H2O2 in the absence of EGT biosynthesis. This could further indicate a shift towards attempting to synthesize EGT in the mutant, given that histidine is a key biosynthetic precursor of EGT”, which is pertinent to claim 5.
Sheridan also teaches “A log2 2.22-fold increase in a putative sulphite reductase (AFUA_2G15590; Supplementary Table S2) in egtA26933 under oxidative stress compared to wild-type indicates an increased need for sulphur in Δ egtA26933, which could reflect attempted EGT production or an increase in GSH biosynthesis, which is pertinent to claim 5.
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It would have been obvious to one of ordinary skill in the art to combine the teachings of Chiang and Sheridan by using the complete BGC refactoring strategy and heterologous expression platform in Aspergillus nidulans based on the afo regulon taught by Chiang and the ergothioneine genes of Aspergillus fumigatus taught by Sheridan, thereby arriving at the invention of claim 5. Since Sheridan teaches a key ergothioneine (EGT) biosynthetic gene in Aspergillus fumigatus and reveal new insights into systems biology of EGT biosynthesis and functionality in fungi, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claims 6, 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over rejected under 35 U.S.C. 103 as being unpatentable over Chiang et al. (Published 2021; hereafter Chiang; PTO-892) as applied to claims 1-2, 7-11, 15 in view of Ru et al. (Published April 21, 2020; hereafter Ru; PTO-892), and further view of Paranjape et al. (Published May 20, 2015; hereafter Paranjape; PTO-892).
Chiang teaches all the limitations of claim 1-2, 7-11, 15 as fully disclosed above and incorporated herein.
However, neither Chiang or Ru teach Asperbenzaldehyde or replacing the promoter of the alcR gene with the constitutive gpdA promoter in the nuclear genome as claims 6, 12.
Neither Chiang or Ru teach specifically “replacing the promoter of the afoA gene with the gpdA promoter and inserting an additional copy of the afoA gene under control of the afoE promoter in the nuclear genome thereby forming a positive feedback loop that generates high levels of both AfoA and asperbenzaldehyde” as claim 13.
Paranjape teaches Aspergillus nidulans secondary metabolites for their ability to inhibit tau aggregation in vitro using an arachidonic acid polymerization protocol. One aggregation inhibitor identified was asperbenzaldehyde, an intermediate in azaphilone biosynthesis; new class of anti-tau aggregation compounds with a novel structural scaffold, which is pertinent to claim 6.
Paranjape teaches a number of strains with various promoter combinations and used a variety of induction conditions to maximize asperbenzaldehyde production, which is pertinent to claim 6.
Paranjape teaches best yields of asperbenzaldehyde were obtained with strain LO8355 (pyrG89, pyroA4, riboB2, nkuA::argB, stcJ::AfriboB, AN1029(p):: AfpyrG-alcA(p), AN1033::AfpyroA, alcR(p)::ptrA-gpdA(p)), which is pertinent to claim 6, 12-13.
Paranjape teaches AN1033 (AfoD) is replaced with the AfpyroA gene to interrupt the asperfuranone biosynthesis pathway causing asperbenzaldehyde to accumulate in the strain LO8355, which is pertinent to claim 6, 12-13.
Paranjape teaches the promoter of asperfuranone biosynthesis transcription factor AN1029 (AfoA) (using the AspGD nomenclature (http://aspergillusgenomes.org/)) is replaced with the highly inducible alcA promoter and the alcR promoter is replaced with the strong, constitutive gpdA promoter (−1241 to −1), which is pertinent to claims 6, 12-13.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Chiang and Paranjape by replacing the promoters and inserting an additional copy of the afoA gene under control of the afoE promoter in the nuclear genome forming a positive feedback loop that generates high levels of both AfoA and asperbenzaldehyde, thereby arriving at the invention of claims 6, 12-13. Since Paranjape teaches best yields of asperbenzaldehyde were obtained with Aspergillus nidulans strain LO8355 which has the stronger constitutive promoter gpdA, leading to higher expression levels of AfoA for the specific activation of the refactored BGC and production of the encoded molecule, which, would be in similar abundance as asperfuranone as taught by Chiang, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly
or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claim 14 are rejected under 35 U.S.C. 103 as being unpatentable over rejected under 35 U.S.C. 103 as being unpatentable over Chiang et al. (Published 2021; hereafter Chiang; PTO-892) as applied to claims 1-2, 7-11, 15-18 above in view of Ru et al. (Published April 21, 2020; hereafter Ru; PTO-892), and further view of Oakley et al. (US Pat. 10118945 B2; hereafter Oakley; PTO-892).
Chiang teaches all the limitations of claim 1-2, 7-11, 15 as fully disclosed above and incorporated herein.
However, neither Chiang or Ru specifically teach deleting “the entire emericellamide biosynthetic gene cluster (genes easA-easD)” in the nuclear genome as claim 14.
Oakley teaches modified fungal strains having deleted gene clusters selected from the group of gene clusters responsible for the biosynthesis of sterigmatocystin, emericellamides, asperfuranone, monodictyphenone, terrequinone, F9775A, F9775B, asperthecin, and both portions of the split cluster that makes austinol and dehydroaustinol, which is pertinent to claim 14. See for example, abstract; Column 3-4; Table 1; lines 21-15.
Oakley teaches the modified fungal strains include A. nidulans, which is pertinent to claim 14.
Oakley teaches modified fungi, and in particular to modified Aspergillus nidulans, methods of using the modified strains for production of compounds, such as pharmaceutically useful compounds, and compounds made by the modified fungus, which is pertinent to claim 14. See for example, column 1
Oakley teaches that “to reduce the secondary metabolite background in Aspergillus nidulans and minimize the rediscovery of compounds and pathway intermediates, a “genetic dereplication” strain in which eight of the most highly expressed secondary metabolite gene clusters (more than 244,000 base pairs deleted in total) deleted. This strain has allowed the discovery of a novel compound designated as aspercryptin and also to propose a biosynthetic pathway for the compound”, which is pertinent to claim 14.
Oakley teaches methods for making compounds by culturing the fungus in a growth media and separating the compound from the fungus and/or separating the compound from the growth media are included, as are the compounds and compositions comprising them, which is pertinent to claim 14. See for example, claim 1.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Chiang and Ru by genetically modifying Aspergillus nidulans, including deleting an entire cluster of genes for upgrading intermediate oxidation products formed by catalytic degradation of linear and/or branched alkanes, polystyrenes, or mixtures thereof for microbial production of chemicals with high value, thereby arriving at the invention of claim 14. Since Oakley teaches the gene clusters responsible for the biosynthesis of sterigmatocystin and emericellamides and a “genetic dereplication” strain in which eight of the most highly expressed secondary metabolite gene clusters (more than 244,000 base pairs deleted in total) deleted to reduce the secondary metabolite background in A. nidulans and minimize the rediscovery of compounds and pathway intermediates, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly
or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over rejected under 35 U.S.C. 103 as being unpatentable over Chiang et al. (Published 2021; hereafter Chiang; PTO-892) as applied to claims 1-2, 7-11, 15-18 above in view of Ru et al. (Published April 21, 2020; hereafter Ru; PTO-892), and further view of Miyazawa et al. (Published 2016; hereafter Miyazawa; PTO-892).
Chiang teaches all the limitations of claim 1-2, 7-11, 15 as fully disclosed above and incorporated herein.
However, Neither Chiang or Ru deleting the agsB gene encoding an a-1,3-glucan synthase as claim 19.
Miyazawa teaches many filamentous fungi, such as those in genus Aspergillus, secrete commercially valuable enzymes and metabolites and are therefore of high value to the fermentation industry, which is pertinent to claim 19.
Miyazawa teaches that although filamentous fungi secrete higher levels of these valuable enzymes and metabolites than yeasts and bacteria, under liquid culture conditions the hyphae of filamentous fungi often clump together to form large pellets, which prevents the establishment of high cell densities under liquid culture conditions. Therefore, preventing pellet formation is crucial for improving the productivity of commercial fermentation processes, which is pertinent to claim 19.
Miyazawa teaches Aspergillus nidulans mutants in which the agsB gene encoding the major α-1,3-glucan synthase was disrupted (agsBΔ) lost most of the α-1,3-glucan from their cell wall and formed dispersed hyphae in liquid culture rather than pellets, which is pertinent to claim 19.
Miyazawa teaches the approach should be applicable to other industrial fungi that have α-1,3-glucan in their cell walls.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Chiang and Ru by genetically modifying Aspergillus nidulans, including deleting the agsB gene encoding an a-1,3-glucan synthase, since preventing pellet formation is crucial for improving the productivity by disrupting the agsB gene encoding the major α-1,3-glucan synthase in A. nidulans resulted in the lost most of the α-1,3-glucan from their cell wall and formed dispersed hyphae in liquid culture rather than pellets as taught by Miyazawa, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly
or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Also, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, Chiang teaches a product (and method) that only differs from the claimed invention by the substitution of a single component (i.e. substitution of a Biosynthetic Gene Clusters BGCs); the substituted element (i.e. afo regulon) was already known and known to function as a biosynthetic gene cluster, therefore no change in the function of the substituted element occurred; and one of ordinary skill in the art would be capable of choosing a BGCs and the afo regulon, such as replacing the coding regions of afoE and afoD with the A. fumigatus egt1 (Afu2g15650) and egt2 (Afu2g13295) disclosed as being useful with a reasonable expectation of success (i.e. the substitution of the element would lead to predictable results), particularly because Chiang teaches an efficient, cloning-free strategy for the cluster refactoring and total biosynthesis of fungal natural products (NPs) by inserting the targeted Biosynthetic Gene Clusters BGCs into the afo regulon of Aspergillus nidulans. In addition, the utility of the system by creating strains that can synthesize high-value NPs, citreoviridin (1), mutilin (2), and pleuromutilin (3), with good to high yield and purity has shown to be successful and potentially applicable to many others Biosynthetic Gene Clusters BGCs. “This platform can be used not only for producing NPs of interests (i.e., total biosynthesis) but also for elucidating cryptic biosynthesis pathways” as taught by Chiang.
Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 20-26, 28-46 are rejected under 35 U.S.C. 103 as being unpatentable over rejected under 35 U.S.C. 103 as being unpatentable over Chiang et al. (Published 2021; hereafter Chiang; PTO-892) as applied to claims 1-2, 7-11, 15-18 above in view of Ru et al. (Published April 21, 2020; hereafter Ru; PTO-892), and further view of Ramesh et al. (US 20180029027 A1; hereafter Ramesh; PTO-892).
Chiang teaches all the limitations of claim 1-2, 7-11, 15 as fully disclosed above and incorporated herein.
However, neither Chiang or Ru specifically teach a catalyst system that includes one or more catalysts, as claim 20.
The one or more catalysts include a transition metal- containing catalyst, as claim 21.
The one or more catalysts include MeReO3 and oxides and halides of Co, Mn, Cu, and Re, as claim 22.
The one or more catalysts include Fe(acac)2 or Fe(acac)3, as claim 23.
The catalyst system includes a cocatalyst, as claim 24.
The cocatalyst includes hydroxylated amines, as claim 25.
The cocatalyst includes hydroxysuccinamide (NHS) or hydroxylamine, as claim 26.
The co-catalyst includes include NO, as claim 28.
Claims 29-46 are iterated in claims 2-19, respectively.
Ramesh teaches a catalyst for recycling a plastic chosen from polyethylene, polypropylene, polystyrene, and combinations thereof includes a porous support having an exterior surface and at least one pore therein, a depolymerization catalyst component comprising a metallocene catalyst disposed on the exterior surface of the porous support, and a reducing catalyst component disposed in the at least one pore. Moreover, the reducing catalyst component comprises a transition metal selected from the group of iron, nickel, palladium, platinum, and combinations thereof. The at least one pore in the porous support has an average pore size of 10 Angstroms, which is pertinent to claims 20-21, 23.
Ramesh teaches oxide catalyst may be or include one or more oxides of beryllium, magnesium, calcium, strontium, barium, radium, or combinations thereof. In certain embodiments, the Group IIA oxide catalyst is further defined as magnesium oxide, calcium oxide, barium oxide, and/or combinations thereof, which is pertinent to claim 22. See for example paragraph [0049].
Ramesh teaches “decomposing the plastic may further include and/or be utilize one or more of a plurality of modifiers. It is contemplated that the modifier may be added to the depolymerization catalyst and/or the co-catalyst. Although any modifier known in the art may be used, typically, the modifier is selected from the group of carboxylic acid esters, amines, cycloalkyltrienes, fluoride ions, ethers, ketones, phosphines, organophosphates, and combinations thereof, which is pertinent to claims 23-26, 28. See for example, paragraph [0060].
Claims 29-36 are rejected as they are dependent of claim 20. Claims 37-43 are rejected as they are dependent of claim 36. Claims 44 is rejected because the claim is dependent of claim 43. Claim 45 is rejected because is dependent of claim 44. Claim 46 is rejected because the claim is dependent of claim 45.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Chiang and Ru by utilizing a method to catalytically degrade linear and/or branched alkanes or polypropylene in an oxidizing environment to form intermediate oxidation products with a catalyst system that includes one or more catalysts such as towards utilization of such products as feedstocks for microbial production of chemicals with high value, such as asperbenzaldehyde and mutilin, thereby arriving at the invention of claims 20-26, 28-46. Since Ramesh teaches methods of plastic degradation (depolymerization) using catalyst system, including a cocatalyst such as hydroxylated amines and oxides can effectively produce feedstocks for production of chemicals with high value by the genetically modified Aspergillus nidulans of Chiangthe synthetic plastics of Ru can be used as feedstocks for production of chemicals with high value by the genetically modified Aspergillus nidulans of Chiang, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
Claim 27 are rejected under 35 U.S.C. 103 as being unpatentable over rejected under 35 U.S.C. 103 as being unpatentable over Chiang et al. (Published 2021; hereafter Chiang; PTO-892) as applied to claims 1-2, 7-11, 15-18 above in view of Ru et al. (Published April 21, 2020; hereafter Ru; PTO-892), and further view of Ramesh et al. (US 20180029027 A1; hereafter Ramesh; PTO-892) as evidenced by Bijpost (US 20220219355 A1; hereafter Bijpost; PTO-892).
Chiang teaches all the limitations of claim 1-2, 7-11, 15 as fully disclosed above and incorporated herein.
However, neither Chiang or Ru specifically teach the co-catalyst includes N-hydroxyphthalimide (NHPI), as claim 27.
Bijpost teaches succinic anhydride, which is pertinent to claim 27. See for example, paragraph [0016].
It would have been obvious to one of ordinary skill in the art to modify the teachings of Chiang and Ru by utilizing a method to catalytically degrade linear and/or branched alkanes or polypropylene in an oxidizing environment to form intermediate oxidation products including the co-catalyst, N-hydroxyphthalimide (NHPI) towards utilization of such products as feedstocks for microbial production of chemicals with high value, such as asperbenzaldehyde and mutilin, thereby arriving at the invention of claim 27. Since Bijpost teaches methods of plastic degradation (depolymerization) using catalyst system, including the co-catalyst includes N-hydroxyphthalimide (NHPI) can effectively produce feedstocks for production of chemicals with high value by the genetically modified Aspergillus nidulans of Chiang, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly
or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Also, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, Chiang teaches a product (and method) that only differs from the claimed invention by the substitution of a single component (i.e. substitution of catalyst and/or co-catalyst); the substituted element (i.e. transition metals or hydroxyphthalimide (NHPI) was already known and known to function as co-catalyst in methods to catalytically degrade linear and/or branched alkanes or polypropylene, therefore no change in the function of the substituted element occurred; and one of ordinary skill in the art would be capable of choosing a catalyst and/or co-catalyst, such as replacing the one or more catalysts include a transition metal- containing catalyst disclosed as being useful with a reasonable expectation of success (i.e. the substitution of the element would lead to predictable results), particularly because Ramesh and Bijpost teaches successful methods for plastic depolymerization, which is highly desirable for degrading linear and/or branched alkanes or polypropylene can effectively produce feedstocks that can be used by the genetically modified Aspergillus nidulans strain of Chiang to producing chemicals with high value. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
No claims are allowable.
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/PRICILA NMN HAUK TEODORO/Examiner, Art Unit 1645
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
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