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 Objections
Claims 34-36 objected to because of the following informalities:
In claims 34-36, “vanillic acid per liter culture medium” should be “vanillic acid per liter of a culture medium.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 31-60 (all pending claims) are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus.”). Regents of the University of California v. Eli Lilly & Co., 119, F.3d 1559, 1568, 43 USPQ2d 1398, 1405 (Fed. Cir. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.”
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice . . ., reduction to drawings . . ., or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” MPEP 2163(II)(3)(a).
Furthermore, a “‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure ‘indicates that the patentee has invented species sufficient to constitute the gen[us].’ See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (‘[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.’). ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).” MPEP 2163(II)(3)(a).
Claim Scope
"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." MPEP 2113(I). Claim 31 sets froth the structure of a product (i.e. a non-GMO mutant strain of Amycolaptosis sp.) in terms of a product-by-process such that the scope of claim 31 includes non-GMO mutant strains made by means that are not produced by exposure to a mutagen.
In view of the above, claim 31 claims any non-GMO mutant strain of Amycolaptosis of any structure having the functional properties of producing vanillin and metabolizing vanillin to vanillic acid as to have less degradation of vanillin to vanillic acid as recited in claim 31. Further, claims 33-36 recite specific functional values of amounts of vanillic acid per liter (specific values of less than 0.5 or 0.25 grams per liter) after 24 or 44 hours after ferulic acid is initially fed.
With respect to claims 31 and more specifically with respect to claims 33-36, the amount of vanillic acid produced including an absolute amount of 0.5 or 0.25 grams per liter less as recite is dependent upon culture conditions (e.g. temperature, substrate concentration, etc.) that are not recited in the claims. For example, Ma et al. (Effect of bioconversion conditions on vanillin production by Amycolaptosis sp. ATCC 39116 through an analysis of competing by-product formation, Bioprocess Biosyst Eng. 37, 2014, 891-99), page 896 (left col.) sets forth:
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As such, an embodiment of any of claims 31 and 33-36 includes a non-GMO mutant with a structural mutation not described by the specification that has less accumulation of less than 0.25 g/L vanillic acid with 9 g/l of ferulic acid substrate but nerveless more than 0.5 g/L of vanillic acid accumulation at some unrecited higher concentration of ferulic acid. That is, a non-GMO strain is an embodiment of the claims provided there is some hypothetical culture condition that results in less vanillic acid accumulation as recited even if there are other unrecited culture conditions that do not result in less vanillic acid accumulation or do not have reduced vanillic acid accumulation meeting the features of claims 33-36.
Regarding claims 37-45, while these claims recite mutation to certain genes and/or certain Sequence Identifiers, the genus of mutations recited include those mutations that do not inactivate the gene completely. For example, claim 44 recites a nonsense mutation that can result in substitution of a single encoded base pair that does not eliminate activity of enzyme or protein encoded by a gene as recited (e.g. gltBD, echR) and wherein a generic two bp insertion as recited in claim 45 includes those insertions that may not eliminate activity, for example those occurring near the 3’ end of the gene.
Claim 50, similar to claim 31, requires a strain to have a functional property of “converts less vanillin to vanillic acid” having at least one mutation in a gltBD operon. However, consistent with as discussed above, none of claims 50-60 require such mutation to be an inactivating mutation (i.e. removes activity of enzymes encoded by gltB or gltD) and in view of the specification includes mutations as recited in claim 44 discussed above.
Analysis
Specification, example 4, reports:
[00119] Whole genome sequencing was performed with the two selected mutant strains to identify the mutation(s) causing the observed phenotype of reduced degradation of vanillin to vanillic acid. Whole-genome sequencing revealed that the two mutant strains have independent mutations, but both are in genes in the gltBD operon coding for the NADPH-dependent glutamate synthase enzyme complex (locus tags AMY39116_RS0321350 and AMY39116_RS0321345). These mutations are in two subunits of the NADPH-dependent glutamate synthase enzyme complex, which catalyzes the reaction: L-glutamine + 2-oxoglutarate + NADPH + H+-> L- glutamate + NADP+. Mutant strain 6-E11 contains a 2bp insertion in the gltD gene after bp 1161, creating a frameshift and truncating the protein after 45 additional amino acid residues. Mutant strain 12-H11 contains a 2bp insertion after bp3148 in the gltB gene, creating a frameshift and truncating the protein after seven additional amino acids.
The specification reports two mutations to gltD and gltB genes, respectively, that are mutations that inactivate those genes by a frame shift mutation towards the beginning part of the gene such that it is clear that a functional enzyme is not produced. No examples of substitution to gltBD genes that are not inactivating are given including 2 bp insertions that do not result in a truncated GltB protein presumed to have no activity.
“‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.”
Here, mutations in the gltBD gene recited are required to bring about the functional property of reduced vanillic acid production as recited. The specification has working examples demonstrating the same that are inactivating mutations of the gltB or gltD gene. From this disclosure, ordinary artisan cannot predict the operability of non-inactivating mutations that may nevertheless be embodiment mutations (e.g. reduced activity of encoding enzymes that can bring about reduced vanillic acid production) such as a point mutation of a single base as indicated in claim 44.
Further, as discussed above, at least claim 31 does not require a mutation to be in either the gltB or gltD and includes mutations to other genes. ““The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice . . ., reduction to drawings . . ., or by disclosure of relevant, identifying characteristics.” The disclosure of mutations in gltBD is not a disclosure of relevant, identifying characteristics to identify other genes/operons that can have a mutation bringing about the recited decrease in vanillic acid production nor a representative number of species for all possible mutations that can bring about reduction in vanillic acid production.
For this reason, an ordinarily skilled artisan cannot predict the operability of the recited genera of 1) all mutations to gltBD including non-inactivating mutations bringing about reduction in vanillic acid production as recited, and 2) all mutations outside of gltBD mutations bringing about reduction in vanillic acid production as recited.
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 32, 37-45, 47, and 50-60 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 32 recites “The mutant strain according to c,” There is insufficient antecedent basis for this limitation in the claim. Claim 32 does not recite a dependency from any other claim and it is unclear what claim feature provides any literal nor antecedent basis for “The mutant strain according to c.” In the alternative, claim 32 may intend to recite a dependency from another claim. However, in the absence of specifying such claim dependency an ordinarily skilled artisan cannot determine how to avoid infringement of claim 32.
Claim 33 recites the limitation "the culture medium" in line 2. There is insufficient antecedent basis for this limitation in the claim. There is no claim feature that appears to provide any reasonable explicit nor inherent antecedent basis for “the culture medium.” In claim 31.
Claims 37 and 50 recite the limitation "the gltBD operon" in lines 2 and 3, respectively. Claim 38 recites the limitation “the gltB gene” in line 2. Claim 42 recites the limitation “the gltD gene” in line 2. There is insufficient antecedent basis for any of these claims. While a strain of Amycolaptosis may have many endogenous genes, recitation of any specific gene requires a clear antecedent basis that cannot be provided by prior recitation of a generic strain of Amycolaptosis sp.
Claim 47 recites the limitation "the mutagen methyl methanesulfonate" in line 2. There is insufficient antecedent basis for this limitation in the claim. There is no claim feature that appears to provide any reasonable explicit nor inherent antecedent basis for “the mutagen methyl methanesulfonate” wherein claim 31 recites a generic at least one mutagen.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 31-42, 44-46, and 48-56 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fleige et al. (Investigation of the Amycolaptosis sp. Strain ATCC 39116 Vanillin Dehydrogenase and Its Impact on the Biotechnical Production of Vanillin, Appl. Environ. Microbiol. 79, 2013, 81-90) further in view of Vong et al. (Biotechnology of microbial flavors, Functional Foods and Biotechnology, Shetty et al., Eds., Apr. 2020) and Parekh et al. (Improvement of microbial strains and fermentation processes, Appl. Microbial. Biotechnol 54, 2000, 287-01).
Fleige, abstract, sets forth:
The actinomycete Amycolaptosis sp. strain ATCC 39116 is capable of synthesizing large amounts of vanillin from ferulic acid, which is a natural cell wall component of higher plants. The desired intermediate vanillin is subject to undesired catabolism caused by the metabolic activity of a hitherto unknown vanillin dehydrogenase (VDHATCC 39116). In order to prevent the oxidation of vanillin to vanillic acid and thereby to obtain higher yields and concentrations of vanillin, the responsible vanillin dehydrogenase in Amycolaptosis sp. ATCC 39116 was investigated for the first time by using data from our genome sequence analysis and further bioinformatic approaches. The vdh gene was heterologously expressed in Escherichia coli, and the encoded vanillin dehydrogenase was characterized in detail. VDHATCC 39116 was purified to apparent electrophoretic homogeneity and exhibited NAD+-dependent activity toward vanillin, coniferylaldehyde, cinnamaldehyde, and benzaldehyde. The enzyme showed its highest level of activity toward vanillin at pH 8.0 and at a temperature of 44°C. In a next step, a precise vdh deletion mutant of Amycolaptosis sp. ATCC 39116 was generated. The mutant lost its ability to grow on vanillin and did not show vanillin dehydrogenase activity. A 2.3-times-higher vanillin concentration and a substantially reduced amount of vanillic acid occurred with the Amycolaptosis sp. ATCC 39116 Δvdh::Kmr mutant when ferulic acid was provided for biotransformation in a cultivation experiment on a 2-liter-bioreactor scale. Based on these results and taking further metabolic engineering into account, the Amycolaptosis sp. ATCC 39116 Δvdh::Kmr mutant represents an optimized and industrially applicable platform for the biotechnological production of natural vanillin.
Fig. 5 of Fleige describes production of vanillin from ferulic acid by both unmodified Amycolaptosis sp. ATCC39116 having a vanillin dehydrogenase and a corresponding strain with deleted vanillin dehydrogenase vdh gene.
However, Fleige does not show a mutation reducing vanillic acid production as recited in claims 31 and 50 produced by a mutagen or otherwise or such mutation specifically in a gltBD operon. The Amycolaptosis sp. ATCC 39116 [Symbol font/0x44]vdh::Kmr mutant described by Fleige is not considered anticipatory with respect to claim 31 since the same is not a non-GMO mutant, wherein a kanamycin resistance gene is an exogenous nucleic acid sequence.
Fleige indicates that removal of vanillin dehydrogenase activity is advantageous for commercial production of vanillin. “For an improved vanillin production process using the actinomycete
Amycolaptosis sp. ATCC 39116, whose 16S rRNA gene sequence is identical to that of Amycolaptosis sp. HR167, the whole genome was sequenced to identify enzymes involved in vanillin catabolism” and the identified vanillin dehydrogenase gene deleted with recombinant DNA methods as indicated above. Fleige, pages 81-82, bridging.
Vong discusses the use of biotechnology for production of flavor compounds including vanillin in section 10.4.1. “Considering the lucrative appeal of GMOs for microbial favor production but the general negative consumer perception of GMOs, non-GMO techniques may offer a win-win solution. The technicalities of non-GMO techniques are such that the desirable microorganisms obtained can bypass the legal GMO definition. These techniques include clonal selection, random or site-directed mutagenesis, hybridization and adaptive evolution. The application of some of these methods has been elaborated in Section 10.4.2.4 to select for microorganisms used in winemaking, although the high cost and tedious effort involved limit their widespread use in the food industry.” Vong, page 200-01, bridging columns.
As discussed, Fleige is directly concerned with production of vanillin in the food and fragrance industry. However, the [Symbol font/0x44]vdh deletion mutant taught by Vong is a GMO microorganism. Vong teaches that it is particularly desirable to develop non-GMO microorganisms for flavor production that “can bypass the legal GMO definition.” As far as Fleige as discussed above teaches that a Amycolaptosis sp. ATCC 39116 strain with deletion of vanillin dehydrogenase vdh gene is beneficial for vanillin production, an ordinarily skilled artisan would have been motivated to “bypass the legal GMO definition” by developing a non-GMO strain having deletion of the same gene. While Vong teaches that development of microorganisms by non-GMO techniques can be tedious, Fleige already demonstrates that a single gene deletion can of the vdh gene can bring about the desired property of reduced vanillic acid production.
Vong directly describes “random or site-directed mutagenesis,” which are well-established techniques in the prior art as reviewed by Parekh as follows (page 289, right col.):
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Parekh, page 290, bridging cols., describes screening in random/mutagenesis wherein mutants within a population are randomly picked and tested for ability to produce the metabolite. In view of Fleige, an ordinarily skilled artisan at time of filing would have readily understood that the property to be screened for is production of vanillin with reduced vanillic acid production. As such, in view of the teachings of Vong and Parekh, an ordinarily skilled artisan at the time of filing would have been motivated to produce a non-GMO strain of Amycolaptosis with removal of the taught vdh gene by random mutagenesis using any of the mutagens from Table 1 of Parekh in order to bypass the regulatory/legal definition of a GMO microorganism wherein GMO microorganisms have a negative consumer perception as taught by Parekh.
Upon identification of a mutant strain of Amycolaptosis sp. ATCC 39116 produced by random chemical mutagenesis (i.e. exposure to a mutagen) having deleted vdh gene, Fleige, Fig. 5(C), indicates that a Amycolaptosis sp. ATCC 39116 strain with deleted vdh gene (regardless of such a strain is produced), has dramatically reduced vanillic acid production when cultured in a culture medium with 2 mM ferulic acid wherein after 30 hours ferulic acid production is less than 0.5 mM. Since the molecular weight of vanillic acid is about 168.14 g/mol, 0.5 mM is equivalent to about 84 mg/L of vanillic acid. As such, it is clear that after 24 or 44 hours of culturing, vanillic acid production will be significantly less than 0.25 grams (250 mg) of vanillic acid per liter of culture as recited in claims 33-36.
Regarding claims 37-42 and 50-56 requiring mutation/deletion of a gltB or gltD gene, the claims do not require that an embodiment mutant strain be isolated. That is, an embodiment of claims 37-42 and 50-56 can be one mutant cell with a mutation/deletion of a gltB or gltD gene formed after treatment with a mutagen located within a population of millions (or more of cells). As explained by Parekh, the treatment with a mutagen causes random mutagenesis.
"The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." MPEP 2145(II). Here, the specification evidences that treatment of a population of Amycolaptosis sp. ATCC 39116 with a chemical mutagen can produce mutations in gltB or gltD gene including a 2 bp frame shift wherein Table 1 of Parekh indicate that various mutagens including alkylating agents produce missense or nonsense mutations (e.g. shift in codons from GC to AT producing codon changes). It is not inventive to discover that a random mutagenesis technique by exposure of a mutagen to a large population of cells can result in some cells having a deactivating mutation to gltB or gltD genes, which the specification evidences results in a reduction of vanillin degradation to vanillic acid as recited in claims 31 and 50 (i.e. an advantage that naturally flows from following the suggestion of the prior art).
Regarding claims reciting SEQ ID NO: 1 or SEQ ID NO: 3, the specification evidences that SEQ ID NO: 1 and 3, respectively, are the encoding sequences for gltB and gltD genes in Amycolaptosis sp. ATCC 39116 such that gltB and gltD genes endogenous to Amycolaptosis sp. ATCC 39116 as taught by Fleige.
Regarding claim 46, such a mutant Amycolaptosis sp. ATCC 39116 strain produced by exposure to a mutagen will not have introduced exogenous genetic material (i.e. non-GMO).
Regarding claims 48 and 49, Fleige teaches that any strain of Amycolaptosis sp. ATCC 39116 can be used to produce vanillic acid as described in the legend of Fig. 5 by culturing in an appropriate medium containing ferulic acid substrate wherein HPLC analysis as described in within the broadest reasonable scope of “recovering the produced vanillin.” Regarding, feeding ferulic acid t the mutant strain for enough time to allow conversion of ferulic acid to vanillin, this is satisfied by providing the initial amount of 2 mM ferulic acid in a culture medium as described in Fig. 5 of Fleige. As set forth in para. [00108] of the specification: “The total amount of substrate can be either fed in one step, in two or more feeding- steps, or continuously.” The initial growth of Amycolaptosis sp. ATC 39116 in Caso medium and harvest during stationary phase growth, followed by washing of cells and “cells were resuspended in 1,000 ml of the same buffer containing 2 mM ferulic acid” is within the broadest reasonable interpretation of feeding such cells in one step.
Claim(s) 31-42, and 44-56 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fleige et al. (Investigation of the Amycolaptosis sp. Strain ATCC 39116 Vanillin Dehydrogenase and Its Impact on the Biotechnical Production of Vanillin, Appl. Environ. Microbiol. 79, 2013, 81-90), Vong et al. (Biotechnology of microbial flavors, Functional Foods and Biotechnology, Shetty et al., Eds., Apr. 2020) and Parekh et al. (Improvement of microbial strains and fermentation processes, Appl. Microbial. Biotechnol 54, 2000, 287-01) as applied to claims 31-42, 44-46, and 48-56 above, and further in view of Kondo (Chapter 26: Comparative mutagenicity of methyl methanesulfonate and ethyl methanesulfonate, Comparative chemical mutagenesis, Serres et al. (eds.), 1981, 743-85).
Claims 31 and 47 recite a mutant strain as a product-by-process and therefore do not require that embodiment mutant strains be made by exposure to any specific mutagen including methyl methanesulfonate. Regardless, claim 47 is considered to be further limiting of claim 31 since the quality of mutations introduced by different classes of mutagens are different.
As discussed, Parekh, Table 1, teach the use of several mutagen agents including ethyl methanesulfonate as suitable for inducing random mutagenesis. Kondo teaches that the related mutagen methyl methanesulfonate is also known in the prior art wherein “Methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) are highly mutagenic in lower organisms.” Kondo, page 743. As such, in view of Parekh specifically teaching EMS, an ordinarily skilled artisan at time of filing would have been further motivated to employ highly similar known mutagens including MMS since “MMS and EMS are mutagenic in bacteriophages, bacteria, . . . and they induce almost all kinds of genetic effects.” Kondo, pages 780-81.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 31-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 37-72 of copending Application No. 18/267,478 in view of
The copending claims recite:
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The rejections under 35 U.S.C. 103 stated above are incorporated herein by reference.
At least copending claim 37 does not require any specific structure but only function for producing vanillin. However, some structure is needed to implement embodiments of copending claim 37. Fleige, as discussed above, further discusses production of vanillin with a mutant Amycolaptosis sp. ATCC 39116 (vdh gene mutant) producing over 6 mM vanillin, which is equivalent to 0.912 g/L (molecular weight of vanillin 152.15 g/mol). Fleige, Fig. 5(B). As such, forming a non-GMO Amycolaptosis strain by exposure to a mutagen as discussed in the rejections under 35 U.S.C. 103 is an embodiment of copending claim 37 and meets the features of claims 31-42 and 44-56 as discussed above. As such, by following the suggestions of the cited prior art discussed above and ordinarily skilled artisan would have been motivated to make embodiments of the copending claims that are further embodiments of the rejected claims. Further, the current specification suggests that any Amycolaptosis sp. ATCC 39116 having deletion of functional expression of a gltD or gltB gene that can be produced by exposure to a mutagen will produce at least 0.5 g/L of vanillin as shown in Fig. 2 of the specification, strains 6-E11 and 12-H11.
Regarding claims 43 and 57, SEQ ID NO: 5 of the copending claims is the amino acid sequence encoded by the nucleic acid sequence of SEQ ID NO: 5 of the pending claims (claim 41). As such, copending claim 41 suggests that the encoding gene as recited in current claim 45 have a mutation as to produce a protein having a mutation. That is, it would have been obvious at the time of filing to start with a Amycolaptosis according to copending claim 41 and subject the same to chemical mutagenesis for the reasons discussed in the rejection under 35 U.S.C. 103 in order to decrease production of vanillic acid.
This is a provisional nonstatutory double patenting rejection.
Examiner’s comment regarding prior art
Practice of claims 59 and 60 are understood to require a mutant strain according to claim 50 to be identified from a population and specifically culturing the same to produce vanillin. The prior art without the benefit of the specification does not specifically motivate the culturing of a Amycolaptosis mutant strain with a mutation in a gltBD operon as recited, although the same mutant strain can be present within a population of mutants as discussed above.
Pattrick et al. (Proteomic Profiling, Transcription Factor Modeling, and Genomics of Evolved Tolerant Strains Elucidate Mechanisms of Vanillin Toxicity in Escherichia coli, mSystems 4, 2019, e00163-19) reports proteins that change in abundance in response to vanillin exposure to “identify novel gene targes for future engineering of vanillin-tolerant strains of E. col.” Pattrick, abstract. Table 1 of Pattrick reports GltB is increased 2.8 fold that indicates that increased expression of GltB is beneficial for vanillin tolerance E. coli and by extension in other bacteria. Regardless, Pattrick is a global study of interconnected genes that respond to vanillin stress. While Pattrick reports “Other indicators of osmoprotectant accumulation include the increases in the abundances of glutamate synthase (GltB),” the increase in GltB reported in Tables 1 and 2 of Pattrick is low compared to other proteins and does not sufficiently motivate a specific change of expression of GltB specifically in a strain of Amycolaptosis having a vanillin dehydrogenase. Further, it is uncertain in the art if increased expression of GltB in a strain of Amycolaptosis would decrease vanillic acid production as required by claim 50 wherein the specification is suggestive of no effect or the opposite.
Conclusion
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/TODD M EPSTEIN/Primary Examiner, Art Unit 1652