DETAILED ACTION
This application has a granted petition for participation in the Patent Prosecution Highway (PPH).
“Any claims amended or added after the grant of the request for participation in the Global/IP5 PPH pilot program must sufficiently correspond to one or more allowable/patentable claims in the OEE application. The applicant is required to submit, along with the amendment, a statement certifying that the amended or newly added claims sufficiently correspond to the allowable/patentable claims in the OEE application. If the certification statement is omitted, the amendment will not be entered and will be treated as a non-responsive reply.” 1400 OG 172 (March 18, 2014).
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 .
Election/Restrictions
Applicant’s election without traverse of Group III in the reply filed on 04/20/2026 is acknowledged.
Applicant’s amendment to claim dependencies has significantly affected scope of the claims. In the interest of compact prosecution, claims 22, 27 and 33 are not withdrawn at this time.
Claims 23, 25, 28, 30, 31 and 34 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/20/2026.
Claim Objections
Claims 21, 27 and 29 are objected to because of the following informalities:
Claim 21 recites “An engineered Saccharomyces cerevisiae . . ., wherein two gene modules are inserted into the engineered Saccharomyces cerevisiae.”
Claim 29 recites a “method for constructing the engineered Saccharomyces cerevisiae according to claim 24, comprising the following steps: . . . wherein two gene modules are inserted into the engineered Saccharomyces cerevisiae.”
In claims 21 and 29, the claims appear to recite producing an engineered Saccharomyces cerevisiae by modifying the engineered Saccharomyces cerevisiae. That is, the claims literally read as producing an engineered Saccharomyces cerevisiae by modifying the same Saccharomyces cerevisiae, which circular wherein an engineered Saccharomyces cerevisiae is produced from itself rather than a different Saccharomyces cerevisiae. No rejection under 35 U.S.C. 112(b) is made since the claims are only reasonably understood as requiring that the recited elements be present in any embodiment S. cerevisiae in claim 21 or produced by the method of claim 29 as to have the structure recited in claim 24. Regardless, the claims should be placed in better form by directly stating the structure of an engineered Saccharomyces cerevisiae. For example, in claim 21, an “engineered Saccharomyces cerevisiae for vanillylamine, the engineered Saccharomyces cerevisiae comprising a gene module 1 and a gene modules 2.” In claim 29, “inserting into a Saccharomyces cerevisiae the gene module 1 and the gene module 2.” It is recommended that all claims be presented in some format.
In claims 27 and 29, claims 27 and 29 recite “a gene module 1” and “a gene module 2” that are understood to be the same gene modules recited in independent claim 21. As such, “the gene module 1” and “the gene module 2” should be recited and it is unnecessary to restate the structure of such modules that are already recited in claim 21.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 21, 22, 24, 26, 27, 29, 32, 33 and 35 (all non-withdrawn claims) 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 21 recites:
“the PAL2, C4H, and 4CL2 genes are derived from Arabidopsis thaliana, the HCT and CCoAoMT1 genes are derived from Nicotiana tabacum, the FerB2 gene is derived from Sphingomonas paucimobilis, and the pAMT gene is derived from Capsicum annuum.”
A gene that is “derived from” an organism is not required to be the same as a gene taken directly from such organism. “Derived from” indicates that the gene may be changed in some undefined manner and still be considered to be derived from. However, the specification does not indicate the quantity or quality of change that can be included while still be considered to be “derived from” A. thaliana, S. paucimobilis, N. tabacum or C. annuum. In order to understand how to avoid infringement of claim 21, an ordinarily skilled artisan at the time of filing must determine how to differentiate between 1) a gene having some degree of change as to be considered to be “derived from” A. thaliana, S. paucimobilis, N. tabacum or C. annuum as recited, and 2) a gene having some degree of change as to be considered not “derived from” A. thaliana, S. paucimobilis, N. tabacum or C. annuum as recited. For this reason an ordinarily skilled artisan is unable to determine how to avoid infringement of claim 21.
It is noted that “the PAL2, C4H, and 4CL2 genes are derived from Arabidopsis thaliana, the HCT and CCoAoMT1 genes are derived from Nicotiana tabacum, the FerB2 gene is derived from Sphingomonas paucimobilis, and the pAMT gene is derived from Capsicum annuum” is not understood to mean any gene having the recited function no matter how different from such genes as found in A. thaliana, S. paucimobilis, N. tabacum or C. annuum. Rather, some degree of similarity is considered to be required to such genes as found in A. thaliana, S. paucimobilis, N. tabacum or C. annuum, as recited, even if the outer boundary of such degree of similarity is not defined as discussed above. It is noted that the “derived from” language also appears in dependent claims.
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.
Claims 22, 24, 26, 27, 29, 32, 33 and 35 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).
“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.
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.
The rejected claims recite a gene or promoter sequence having “a nucleotide sequence shown in SEQ ID NO:” 8-30, 32, 36-39, and 45-48 [all Sequence Identifiers in rejected claims intended to be recited in event any are inadvertently omitted]. Each indicated gene has a particular biological function; for example, pheA gene encodes a bifunctional chorismate mutase prebenzoate dehydratase. The functional identity of all recited genes are provided in the specification or otherwise understood in the art and are not listed herein by detail but will be referred to as gene activity or activity of the gene. Promoter sequences are understood to have the function of a promoter in S. cerevisiae.
The recitation of indefinite articles a/an indicates a genus of plural sequences such that reference to a nucleotide sequence shown in SEQ ID NO:” 8-30, 32, 36-39, and 45-48 refers to any fragment of these Sequence Identifiers including as few as two consecutive nucleotides.
As such, the rejected claims recite genera of genes encoding proteins with specific functions and promoters defined as requiring only a few (and as few as two) nucleotides as found in the recited Sequence Identifiers. “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,” and a “‘representative number of species’ means that the species which are adequately described are representative of the entire genus.” Here, the specification only discloses promoters and genes encoding proteins with specific function having 100% identity to the full-length sequences of the various recited Sequence Identifiers. The specification has no description that can allow for an ordinarily skilled artisan at the time of filing to make a reasonable identification of member species of the discussed genera having the same function as the full-length of the recited sequences but only requiring a small fragment thereof.
That is, the recited genera of genes and promoters includes species having very low sequence identity to any of the recited Sequence Identifiers (e.g. less than 30%, less than 20%, less than 10% identity) wherein members of the recited genera cannot be reasonably identify based off the disclosure of only full-length nucleotide sequences having the functionality recited by the claims, wherein species that are members of the discussed genera include those that are 1) wild-type or naturally-occurring sequences otherwise known in the art, and 2) are non-naturally occurring or variant sequences requiring with no specific minimum identity to the recited Sequence Identifiers but nevertheless maintaining the same function of the recited genes and promoters.
“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." Here, when presented with any potential nucleotide sequence with little identity (e.g. less than 30%, less than 20%, less than 10% identity) to any of the recited Sequence Identifiers, it is not reasonably possible to determine if the same 1) has activity of a gene or promoter as recited as to be an embodiment of the claims, or 2) lacks such activity as to not be an embodiment of the claims. For these reasons, the as-filed specification lacks a sufficient written description of the various recited genera of genes and promoters as discussed above.
This rejection can be obviated by amending the claims to recite “having the nucleotide sequence as shown in” SEQ ID NO: 8-30, 32, 36-39, and 45-48. It is recommended that similar claim language in withdrawn claims also be appropriately reviewed.
Examiner’s statement regarding prior art
As an initial matter, applicant has published a similar disclosure as Zhao et al. (Yeast-Based Whole-Cell Factory for the Ecofriendly Synthesis of Vanillylamine as a Critical Step toward Capsaicin Production, ACS Sustainable Chem. Eng. 11, May 2023, 7683-91), wherein Fig. 1 provides some more detail regarding reactions catalyzed by the recited genes.
Zhao report that “vanillylamine production from glucose in microorganisms has not yet been reported.” Zhao, page 7683, left col. A search of the prior art indicates that this statement of Zhao is technically true. However, production of vanillin from glucose has been reported in the prior art.
The closest identified prior art is Qiu et al. (De novo biosynthesis of vanillin in engineered Saccharomyces cerevisiae, Chem. Eng. Sci. 263, 2022, 118049). As described by Qui, page 2, left col.:
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Fig. 4A of Qui also shows an alternative pathway for vanillin production beginning from phenylalanine, which requires two separate hydroxylation steps to produce caffeoyl-CoA. The pathway for production of vanillin in Fig. 4A of Qui involves expression of PAL, C4H, 4CL (ligase), HCT and CCoAOMT genes (the black portion of Fig. 4A) similar to as recited. However, “The orange part was the route selected in this paper.” The black and the orange portion of Fig. 4A includes p-courmaric acid as common early intermediate. As such, even wherein PAL (phenylalanine ammonia lyase) is expressed to utilizing phenylalanine, Qui suggests that expression of the orange pathway (C3H, COMT and FCS) would remain advantageous, although the alternate pathway is not disparaged.
Qui reports the final conversion of feruloyl-CoA to vanillin is catalyzed by ECL (enoyl-CoA hydratase/aldolase). Qui, Table 1, reports ECH is from Streptomyces sp. strain V1. Such ECH is distinct from the FerB2 gene from Sphingomonas paucimobilis recited in claim 21. Masai et al. (Cloning and Characterization of the Ferulic Acid Catabolic Genes of Sphingomonas paucimobilis SYK-6, Appl. Environ. Microbiol. 68, 2002, 4416-24), Fig. 1, shows that FerB2 from S. paucimobilis is known to convert feruloyl-CoA to vanillin. Masai, abstract, reports that FerB2 is a homolog to FerB catalyzing the same reaction having only 49% identity to FerB. In order to reach the features of claim 21, Qui would have to be modified to 1) select the black pathway for production of vanillin in Fig. 4A including expression of PAL, and 2) replace expression of ECH with FerB2 as taught by Masai. Without the benefit of applicant’s disclosure, there is not deemed to be sufficient motivation to make both of these changes. A further modification to Qui to produce vanillylamine is also required to reach claim 21, which is not specifically addressed at this time.
The following prior art is also of note and briefly discussed. Caffeoyl-CoA is an intermediate used to produce several desirable products in the prior art. Roussel et al. (U.S. 2025/0019727 A1, filed 11/23/2022), Fig. 5, shows production of ferulic acid or caffeic acid producible from phenylalanine by the action of PAL, C4H, and 4CL to produce p-coumaroyl-CoA that is then convertible to caffeoyl-CoA. The PAL, C4H (cinnamate 4-hydroxylase) and 4CL can be from Arabidopsis thaliana. See Roussel, Table 1. Roussel further teaches that a CCoA3H (coumaroyl-CoA 3-hydroxylase, CCoAoMT1) can be from Nicotiana tabacum (Roussel, para. [0075]) and that a coumaroyl-CoA 3 hydroxylase (CcoA3H37, HCT) can be from Nicotiana tabacum (Roussel, Table 2, SEQ ID NO: 65).
Chen et al. (U.S. 11,459,591 B2), Fig. 1, shows the biosynthesis pathway for capsaicin as found in plants. Chen further discloses synthesis of capsaicinoids by culturing E. coli expressing ACS1 and capsaicin synthase (CS) genes in a medium containing vanillylamine and various fatty acids. Chen, Example 1.
Chen et al. (U.S. 9,951,358 B2) discloses methods of producing capsaicinoids by expressing pAMT and capsaicin synthase (CS) is a cell cultured in the presence of exogenous vanillylamine and fatty acids. See Example 2. Chen does not show production capsaicin from glucose or other fermentable carbon sources.
Conclusion
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/TODD M EPSTEIN/Primary Examiner, Art Unit 1652
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