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 .
Priority
Applicant’s claim for the benefit of a prior-filed U.S. provisional application no. 63/375,684 filed September 14th, 2022, and PCT application no. PCT/US2023/073707, filed September 8th, 2023, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Thus, the earliest possible priority for the instant application is September 14th, 2022.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on March 14th and 17th, 2025 were considered, initialed, and attached hereto. A signed copy of the list of references cited is included with this Office Action.
Status of Claims
Claims 1-17 filed March 14th, 2025 are pending and examined herein.
Claim Interpretation
The term "gene regulatory activity," refers to the ability to affect the expression of an operably linked transcribable DNA polynucleotide, for instance by affecting the transcription and/or translation of the operably linked transcribable DNA polynucleotide. Regulatory elements, such as promoters, leaders, enhancers, introns and 3' UTRs that function in plants are useful for modifying plant phenotypes through genetic engineering, as stated in the instant application [¶45].
The term "heterologous" refers to the combination of two or more DNA polynucleotides (or nucleotide sequences, or DNA sequences) when such a combination is not normally found in nature, as stated in the instant application [¶74]. Examiner notes that the claims have not been rejected under 35 USC § 101 due to the recitation of heterologous even though the recited sequences appear to be found in nature.
The term "operably linked" refers to a first DNA polynucleotide joined to a second DNA polynucleotide, wherein the first and second DNA polynucleotides are so arranged that the first DNA polynucleotide affects the function of the second DNA polynucleotide, according to the instant application [¶67]. The two DNA polynucleotides may or may not be part of a single contiguous DNA polynucleotide and may or may not be adjacent.
The term "transcribable DNA polynucleotide" refers to any DNA polynucleotide capable of being transcribed into an RNA, as detailed in the instant application [¶74].
The term “commodity product” refers to any composition or product which is comprised of material derived from a transgenic plant, seed, plant cell, or plant part containing the recombinant DNA polynucleotide, including seeds, processed seeds, protein concentrate, protein isolate, starch, grains, plant parts, seed oil, biomass, flour and/or meal [¶97].
Improper Markush Grouping
Claims 1-17 are rejected on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of SEQ ID NOs: 1-23 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: Different nucleotide sequences are structurally distinct compounds. The sequences do not appear to share structural sequence similarity based on their different annotations and element types, as defined in Table 1 of the instant disclosure. There is no expectation from the knowledge in the art that the members of these classes will behave in the same way, particularly given that the sequences are annotated as different genes and are further divided into promoter/leader and 3’UTR element types. For example, searching the promoter/leader sequence of SEQ ID NO: 1 will provide no information regarding the 3’UTR sequence of SEQ ID NO: 2, despite the fact that they are both annotated as Inorganic phosphate transporter 2-1, chloroplastic. Based on the different annotation, the variety of sequences do not appear to be functionally equivalent. For example, inorganic phosphate transporters are critical carrier proteins for extracellular inorganic phosphate, while Early nodulin 12-A is a plant gene activated during the early stages of leguminous plants and Rhizobia, demonstrating functional variability and inconsistencies in gene regulatory elements isolated from the different genes.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112(a)
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.
Written Description
Claims 1-17 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 Applicant describes:
A recombinant DNA polynucleotide comprising a DNA sequence with the nucleotide sequences of 1-23, each providing the gene regulatory activity provided in Table 1 of the instant disclosure of promoter or 3’UTR activity of an operably linked coding sequence within a transgenic soybean plant cells, plants, progeny and seeds.
The Applicant does not describe:
Any gene regulatory activity; a fragment of the sequences; or at least 85% identity to the claimed sequences in any transgenic plant, cell or part thereof.
A recombinant DNA polynucleotide comprising any of SEQ ID NOs: 1-23 operably linked to a heterologous transcribable DNA polynucleotide, wherein the sequence of SEQ ID NOs: 1-23 is not providing gene regulatory activity.
The claims are broadly drawn to a recombinant DNA molecule comprising a DNA sequence with at least 85% identity to SEQ ID NOs: 1-23, a fragment of any of SEQ ID NOs: 1-23, and a fragment of unspecified size of the sequence with undefined gene regulatory activity introduced to any transgenic plant.
The instant disclosure only describes the nucleic acid sequences derived from Glycine max with full identity to the claimed SEQ ID NOs: 1-23 with the defined gene regulatory activity as recited in Table 1 of the instant disclosure. For example, the instant disclosure provides the example of SEQ ID NO: 1, which is a promoter/leader sequence of an Inorganic phosphate transporter 2-1, chloroplastic from Glycine max variety A3555 and drives GUS expression when operably linked in stably transformed soybean plants.
The instant disclosure fails to reduce to practice the SEQ ID NOs with full identity to the sequences performing any gene regulatory activity other than the one listed in the table. The instant disclosure states that gene regulatory activity is merely the ability to affect the expression of an operably linked transcribable DNA polynucleotide. This can include promoters, enhancers, silencers, insulators, 3’ UTR etc. By nature of the functionality of these elements, the sequences may not function in performing any gene regulatory activity. The instant disclosure reduces to practice specific element types associated with the claimed SEQ ID NOs [Table 1], but does not reduce to practice that the SEQ ID NOs. may have any gene regulatory activity.
The instant disclosure fails to reduce to practice fragments of the SEQ ID NOs such that they have functional gene regulatory activity, or sequences with 85% identity to the SEQ ID NOs. with gene regulatory activity. The instant disclosure recites that, in some embodiments, fragments of a promoter comprise at least about 50 contiguous nucleotides of a DNA polynucleotide having promoter activity as disclosed and that methods for producing such fragments from a starting promoter polynucleotide are well known in the art [¶50-51]. The Applicant describes that the fragment as disclosed may have the activity of the reference sequence from which it is derived. For 3’UTRs, the Applicants state that prediction of functional and efficient 3’UTRs is difficult because there are no conserved DNA structures that would allow easy prediction [¶12], indicating that a fragment may not confer any functional gene regulatory activity and undue experimentation would be required to determine which fragment of the claimed sequences maintains the functionality.
The instant specification does not describe which fragments confer the functionality or which of the 85% of the nucleotides that must remain to confer functionality; thus, it appears that any nucleotides of any quantity may be deleted, substituted, added and/or inserted with any other nucleotides. The positional changes made within a nucleotide sequence such that the sequence maintains its function of gene regulatory activity successfully are limited. The instant disclosure teaches that the 3’UTR should be able to efficiently and effectively terminate transcription of the transcribable DNA polynucleotide and prevent read -through of the transcript into any neighboring DNA sequence. The 3’UTR should further not cause a reduction in transcriptional activity imparted by other gene regulatory elements.
Genetic variations at 3’UTRs may modify regulatory elements affecting the interaction of the UTRs with proteins and microRNAs (Steri, M. et al. 2018. “Genetic variants in mRNA untranslated regions.” Wiley. Interdiscip Rev RNA. (4):e1474. doi: 10.1002/wrna.1474) [Abstract]. The overall functional consequences include modulation of mRNA transcription, secondary structure, stability, localization, translation, and access to regulators like microRNAs (miRNAs) and RNA-binding proteins (RBPs). Alterations of these regulatory mechanisms are known to modify molecular pathways and cellular processes. Indeed, SNPs, in the UTRs of disease-associated genes were predicted to cause RNA conformational change, with a single A allele generating a conformational change in the folder structure of a long non-coding RNA H19 gene, creating the loss of the target binding site for some miRNA and creating new binding sites for other miRNAs [pg. 10, ¶7].
A sequence identity of 85% allows for great variability in sequence structure. For example, SEQ ID NO: 1 is 2006 nucleotides long, allowing for around 300 substitutions, additions, or deletions. For just substitutions, there are
N
K
x
3
K
ways to choose which of the 2006 positions are changes with 3 possible alternative nucleotides, wherein N is the total sequence length and K is the number of changed nucleotides. This results in around 1.99 x 10619 possibilities for substitution of nucleotides in SEQ ID NO: 1 with 85% sequence identity. The instant disclosure has not reduced to practice any species of the claimed genus other than sequences with full length identity to SEQ ID NOs: 1-23.
Further, as the claims are currently recited, the scope is such that it can be drawn to any recombinant DNA polynucleotide comprising any of SEQ ID NOs: 1-23 operably linked to a heterologous transcribable DNA polynucleotide. As fluorescent reporter genes are heterologous transcribable DNA polynucleotide, a gene with 85% identity to the claimed genes operably linked to a fluorescent reporter gene for a fusion protein may read on the claims and need not have gene regulatory activity as described in the instant specification (See, rejection under 35 USC § 103 detailed below).
Thus, the Applicant does not describe a representative number of polynucleotide sequences falling within the scope of the claimed genus. Applicants fail to describe structural features common to the members of the claimed genus of polynucleotides, i.e., fragments and sequences with 85% identity to the SEQ ID NOs, or provide functional species within this group. Since the genus has not been adequately described by structural features, the functional characteristic of regulatory gene activity, is not sufficient to support the breadth of the claims. Claims 4-8, and 12-17, as well as and 10-11 do not recite further limitations to overcome the above rejection and are thus rejected as they are dependent upon independent claims 1 and 9, respectively
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.
Claims 1-3, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Liu, J. et al. (2016). “Genome-wide analysis of MATE transporters and expression patterns of a subgroup of MATE genes in response to aluminum toxicity in soybean.” BMC Genomics 17, 223, in view of Lu, P. et al. (2019). “Overexpression of Cotton a DTX/MATE Gene Enhances Drought, Salt, and Cold Stress Tolerance in Transgenic Arabidopsis.” Front Plant Sci. 10:299, and PREDICTED: Glycine soja protein DETOXIFICATION 44, chloroplastic (LOC114419124), transcript variant X3, NCBI Reference Sequence: XM_028384731.1, published 03/12/2019.
Claim 1 recites a recombinant DNA polynucleotide comprising a DNA sequence selected from a sequence comprising any of SEQ ID NOs:1-23, wherein said DNA sequence is operably linked to a heterologous transcribable DNA polynucleotide.
Claim 2 recites the recombinant DNA polynucleotide of claim 1, wherein the DNA sequence has at least 90 percent sequence identity to the DNA sequence of any of SEQ ID NOs:1-23.
Claim 3 recites the recombinant DNA polynucleotide of claim 2, wherein the DNA sequence has at least 95 percent sequence identity to the DNA sequence of any of SEQ ID NOs:1-23.
Claim 9 recites a transgenic plant cell comprising a recombinant DNA polynucleotide comprising a DNA sequence selected from the group consisting of: a) a sequence with at least 85 percent sequence identity to any of SEQ ID NOs:1-23;b) a sequence comprising any of SEQ ID NOs:1-23; and c) a fragment of any of SEQ ID NOs:1-23, wherein the fragment comprises gene regulatory activity; wherein said DNA sequence is operably linked to a heterologous transcribable DNA polynucleotide.
Claim 11 recites the transgenic plant cell of claim 9, wherein the transgenic plant cell is a dicotyledonous plant cell.
Regarding claims 1-3, 9, and 11, Liu teaches that the Multidrug and toxic compound extrusion (MATE) family is an important group of the multidrug efflux transporters that extrude organic compounds, transporting a broad range of substrates such as organic acids, plant hormones and secondary metabolites [Abstract]. A total of 117 genes encoding MATE transporters were identified from the whole genome sequence of soybean (Glycine max), which were denominated as GmMATE1 - GmMATE117 []. The relative transcript abundance showed some GmMATE genes such as GmMATE44 mainly expressed in pod and developing seed, suggesting their putative roles during seed development [pg. 6, col. 2, ¶3]. Although the subcellular localization was predicted using WoLF PSORT, they were not confirmed [pg. 11, col. 2, ¶1]. However, Lu teaches the determination of the subcellular localization of DTX/MATE proteins.
Lu teaches that the detoxification efflux carriers (DTX)/multidrug and toxic compound extrusion (MATE) transporters are of significance in the translocation of abscisic acid (ABA), a phytohormone with profound role in plants under various abiotic stress conditions [Abstract]. Lu teaches a genome-wide analysis of the DTX/MATE gene family, transformed a DTX/MATE gene in Arabidopsis and a functional analysis under drought, salt, and cold stress conditions. Lu teaches determination of the subcellular localization of the DTX/MATE protein by fusion to a GFP gene under the regulation of a CaMV 35S promoter [pg. 4, col. 1, ¶2]. This is taken to read on a recombinant polynucleotide comprising a DNA sequence operably linked to a heterologous transcribable DNA polynucleotide, with the GFP being the heterologous transcribable DNA polynucleotide. Lu teaches transformation into epidermal onion cells for observation under a fluorescent microscope (i.e., a transgenic plant cell comprising a recombinant DNA polynucleotide; wherein the plant cell is a dicotyledonous plant cell). As subcellular localization is essential to mapping biological function, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to use such methodology with the GmMATE44/DTX44 gene as taught by Liu.
Liu and Lu do not explicitly teach a DNA sequence selected from the instant claims, however, an NCBI BLAST search revealed numerous predicted Glycine soja and Glycine max protein DETOXIFICATION 44. The NCBI BLAST search against SEQ ID NO: 20 of the instant application revealed high identity to the predicted DETOXIFICATION 44 proteins (see, search alignments below). Given that Liu teaches that GmMATE44 mainly expressed in pod and developing seed, suggesting their putative roles during seed development, but does not teach specific localization of the GmMATE44; given that Lu teaches specific subcellular localization of MATE/DTX genes, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to try the available DTX44 to provide a subcellular localization for mapping the biological function of GmMATE44/DTX44.
As Lu teaches that a GFP is attached (i.e., operably linked) to a DTX gene, and SEQ ID NO: 20 of the instant application has a 100% match to DTX44 in Glycine soja (NCBI Reference Sequence: XM_028384731.1) and 91% match to DTX44 in Glycine max, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to use similar methodology to Lu to observe subcellular localization of a finite number of predicted proteins to understand normal cellular function and potential modifications. One would have been motivated as the GmMATE44/DTX44 gene was predicted to function in seed development, as taught by Liu. One would have reasonable expectation of success in trying a Glycine soja or max gene as the presence and importance of MATE transporter genes in Glycine have been previously demonstrated.
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Thus, Lu, Liu, and NCBI Reference Sequence: XM_028384731.1 render obvious the claimed invention to the extent that the claims are interpreted to mean a DNA sequence of SEQ ID NO: 20 attached to any heterologous transcribable DNA polynucleotide, such as GFP.
Claims 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kovalic, D. et al. “Annotated Plant Genes.” U.S. Patent Application Publication No. US 20070067865 A1. Published 03/22/2007, in view of La Rosa, T. et al. “Soy Nucleic Acid Molecules and Other Molecules Associated With Plants And Uses Thereof For Plant Improvement.” U.S. Patent Application Publication No. US 20160264984 A1. Published 09/15/2016, PREDICTED: Glycine soja protein DETOXIFICATION 44, chloroplastic (LOC114419124), transcript variant X2, mRNA. NCBI Reference Sequence: XM_028384730.1. (2019), and Bernardes, W., et al. (2020). “Plant 3’ Regulatory Regions From mRNA-Encoding Genes and Their Uses to Modulate Expression.” Front. Plant Sci. 11:1252. doi: 10.3389/fpls.2020.01252.
Claim 1 recites a recombinant DNA polynucleotide comprising a DNA sequence selected from the group consisting of: a) a sequence with at least 85 percent sequence identity to any of SEQ ID NOs:1-23; b) a sequence comprising any of SEQ ID NOs:1-23; and c) a fragment of any of SEQ ID NOs:1-23, wherein the fragment comprises gene regulatory activity; wherein said DNA sequence is operably linked to a heterologous transcribable DNA polynucleotide.
Claim 2 recites the recombinant DNA polynucleotide of claim 1, wherein the DNA sequence has at least 90 percent sequence identity to the DNA sequence of any of SEQ ID NOs:1-23.
Claim 3 recites the recombinant DNA polynucleotide of claim 2, wherein the DNA sequence has at least 95 percent sequence identity to the DNA sequence of any of SEQ ID NOs:1-23.
Claim 4 recites the recombinant DNA polynucleotide of claim 2, wherein the DNA sequence has at least 95 percent sequence identity to the DNA sequence of any of SEQ ID NOs:1-23.
Claim 5 recites the recombinant DNA polynucleotide of claim 1, wherein the heterologous transcribable DNA polynucleotide comprises a gene of agronomic interest.
Claim 6 recites the recombinant DNA polynucleotide of claim 5, wherein the gene of agronomic interest confers herbicide tolerance in plants.
Claim 7 recites the recombinant DNA polynucleotide of claim 5, wherein the gene of agronomic interest confers pest resistance in plants.
Claim 8 recites the recombinant DNA polynucleotide of claim 1, wherein the heterologous transcribable DNA polynucleotide encodes a dsRNA, a miRNA, or a siRNA.
Claim 9 recites a transgenic plant cell comprising a recombinant DNA polynucleotide comprising a DNA sequence selected from the group consisting of: a) a sequence with at least 85 percent sequence identity to any of SEQ ID NOs:1-23;b) a sequence comprising any of SEQ ID NOs:1-23; and c) a fragment of any of SEQ ID NOs:1-23, wherein the fragment comprises gene regulatory activity; wherein said DNA sequence is operably linked to a heterologous transcribable DNA polynucleotide.
Claim 10 recites the transgenic plant cell of claim 9, wherein the transgenic plant cell is a monocotyledonous plant cell.
Claim 11 recites the transgenic plant cell of claim 9, wherein the transgenic plant cell is a dicotyledonous plant cell.
Claim 12 recites a transgenic plant, or part thereof, comprising the recombinant DNA polynucleotide of claim 1.
Claim 13 recites a progeny plant of the transgenic plant of claim 12, or a part thereof, wherein the progeny plant or part thereof comprises the recombinant DNA polynucleotide of claim 1.
Claim 14 recites a transgenic seed, wherein the seed comprises the recombinant DNA polynucleotide of claim 1.
Claim 15 recites a method of producing a commodity product comprising obtaining a transgenic plant or part thereof according to claim 12 and producing the commodity product therefrom.
Claim 16 recites the method of claim 15, wherein the commodity product is selected from the group consisting of seeds, processed seeds, protein concentrate, protein isolate, starch, grains, plant parts, seed oil, biomass, flour, and meal.
Claim 17 recites a method of expressing a transcribable DNA polynucleotide comprising obtaining a transgenic plant according to claim 12 and cultivating said plant, wherein the transcribable DNA polynucleotide is expressed.
Regarding claim 1, Kovalic teaches a first nucleic acid sequence, having a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1-463,173 [claim 1]. Kovalic teaches a method of producing a plant containing an overexpressed protein or producing a plant containing reduced levels of a protein comprising transforming the plant with a functional nucleic acid molecule which comprises a promoter region linked to a structural region linked to a 3’ non-translated sequence [¶20-21]. Kovalic teaches that the nucleic acid molecules of the invention may be used to isolate promoters of cell enhanced, cell specific, tissue enhanced, tissue specific, developmentally or environmentally regulated expression profiles. Kovalic teaches that using genomic screening methods and PCR techniques would result in the isolation of useful promoters and transcriptional regulatory elements [¶150]. These methods are known to those of skill in the art and have been described [¶151]. Such genetic elements could be used to enhance gene expression of new and existing traits for crop improvement.
Kovalic also teaches a transformed plant having a nucleic acid molecule which comprises: (A) an exogenous promoter region which functions in a plant cell to cause the production of a mRNA molecule; (B) a structural nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1 through SEQ ID NO: 463,173; and (C) a 3' non-translated sequence that functions in the plant cell to cause termination of transcription and addition of polyadenylated ribonucleotides to a 3' end of the mRNA molecule [¶14]. Kovalic teaches that the DNA polynucleotide can be expressed, via recombinant means [¶82] and that the promoter region functions in a plant cell to cause the production of a mRNA molecule [¶14], teaching that the DNA polynucleotide is transcribable (i.e., a recombinant DNA polynucleotide comprising a DNA sequence, wherein said DNA sequence is operably linked to a transcribable DNA polynucleotide).
SEQ ID NO: 57435 of Kovalic shares 100% identity with SEQ ID NO: 20 of the instant disclosure (i.e., a DNA sequence selected from the group consisting of a) a sequence with at least 85% identity to any of SEQ ID NOs: 1-23). This Glycine soja sequence has been annotated as a transmembrane transport protein in the hypocotyl of etiolated seedlings, as taught by NCBI Reference Sequence: XM_028384730.1.
Kovalic does not explicitly teach that the DNA sequence is operably linked to a heterologous transcribable DNA polynucleotide, however, La Rosa teaches constructs that are useful for production of transgenic plants having at least one improved property as the result of expression of a polypeptide [¶15]. La Rosa teaches that the construct may have a heterologous sequence linked to the gene for enhanced protein activity [¶28], and that a polynucleotide comprising a polypeptide coding sequence may be operably linked to the promoter [¶16] (i.e., wherein sad DNA sequence is operably linked to a heterologous transcribable DNA polynucleotide). La Rosa teaches the same sequences as Kovalic, with SEQ ID NO: 57435 sharing 100% alignment with SEQ ID NO: 20 of the instant application.
Kovalic does not explicitly teach motivation to use the 3’UTR region of SEQ ID NO: 57435, however, Bernardes teaches that the 3’ regulatory regions have a great diversity of cis-regulatory elements directly involved in polyadenylation, stability, transport and mRNA translation, essential to achieve the desired levels of gene expression [Abstract]. After transcription, a wide array of RNA-binding proteins interacts with cis-acting elements located mainly in the 3’ untranslated region, determining the fate of mRNAs in eukaryotic cells. Bernardes teaches that the NOS 3’ regulatory region was used in the production of the first glyphosate-resistant plants, such as soybeans and wheat, but that the rbcS E9 3’ regulatory region has also been used in the generation of glyphosate resistant soybeans [pg. 12, col. 1, ¶1]. Further, Potato plants transformed to express recombinant hepatitis B surface antigen (HBsAg) showed higher levels of HBsAg mRNA when soybean VSP gene 3’ regulatory regions were used, compared to the NOS, demonstrating the applicability in soybean [pg. 11, col. 1, ¶4]. The use of plant 3’ regulatory regions in the construction of vectors has shown to be able to not only optimize, but also to make possible a fine regulation of gene expression, presenting potential superior to 3’ regulatory regions, NOS, OCS and 35S, commonly used in the production of genetically modified organisms [pg. 12, col. 1, ¶3].
In a recombinant DNA polynucleotide comprising a DNA sequence of the 3’ non-translating region of a transmembrane transport gene, such as SEQ ID NO: 57435 of Kovalic, the cis-regulatory elements controlling the stability, translocation, and localization of the 3’UTR would dictate how, when, and where the heterologous transcribable DNA polynucleotide is expressed in the cell.
Thus, Kovalic teaches a recombinant DNA polynucleotide comprising a transcribable DNA polynucleotide and a 3’UTR. Kovalic teaches SEQ ID NO: 57435 with 100% identity to SEQ ID NO: 20 of the instant application, annotated in BLAST as a Glycine soja protein DETOXIFICATION 44, and teaches that regulatory element, such as 3’UTR may be isolated from the disclosed sequence by methodology known in the art. La Rosa teaches that the DNA polynucleotide and regulatory element are operably linked and may be heterologous. Bernardes further teaches that regulatory elements besides the commonly used 3’ regulatory regions, NOS, OCS, and 35S have been found to be superior in the production of genetically modified organisms. It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to isolate the 3’UTR region of SEQ ID NO: 57435 as suggested by Kovalic to enhance gene expression of one of the claimed sequences in the recombinant DNA polynucleotide (SEQ ID NOs: 1-463,173). One would have been motivated to do so over other well-known 3’ UTRs because Bernardes teaches that the 3’ regulatory regions have a great diversity of cis-regulatory elements directly involved in polyadenylation, stability, transport and mRNA translation, essential to achieve the desired levels of gene expression, and teaches use of 3’ regulatory regions of soybean. One would have reasonable expectation of success because SEQ ID NO: 57435 of Kovalic was known at the time of filing and documented to improve agricultural traits.
The use of a heterologous transcribable DNA polynucleotide and operable linkage to a regulatory element was well known in the art at the time of filing, as taught by La Rosa.
Regarding claims 2-3, Kovalic teaches SEQ ID NO: 57435 with 100% identity to SEQ ID NO: 20 of the instant application (i.e., the recombinant DNA polynucleotide of claim 1, wherein the DNA sequence has at least 90 or 95 percent sequence identity to the DNA sequence of any of SEQ ID NOs: 1-23).
Regarding claim 4, Kovalic teaches that the regulatory element may be isolated from the referenced genes, including SEQ ID NO: 57435 (i.e., wherein the DNA sequence comprises gene regulatory activity).
Regarding claim 5, Kovalic teaches the identification and isolation of plant genes belonging to biochemical and regulatory pathways important in the development of nutritionally and agriculturally enhanced crops and products from maize, soybean, rice, cotton, sorghum, wheat Arabidopsis and teosinte, such as the transcribable DNA polynucleotide, SEQ ID NO: 57435 (i.e., wherein the heterologous transcribable DNA polynucleotide comprises a gene of agronomic interest) [¶6].
Regarding claims 6-7, La Rosa, which teaches the same polynucleotide as Kovalic, teaches that the polynucleotides of the invention include traits of interest such as herbicide tolerance, pest stress resistance [¶19, ¶40] (i.e., wherein the gene of agronomic interest confers herbicide tolerance in plants; confers pest resistance in plants).
Regarding claim 8, Kovalic teaches that posttranscriptional gene silencing can result in virus immunity or gene silencing in plants and teaches that this may be induced by dsRNA [¶140]. Kovalic teaches that one or more of the nucleic acids of the invention may be introduced into a plant cell and transcribed to result in posttranslational gene silencing.
Regarding claim 9, Kovalic teaches a transgenic plant comprising the nucleic acid molecule comprising a promoter region, a structural nucleic acid molecule, and a 3’ non-translated sequence [claim 6]. Kovalic teaches that the nucleic acid molecules of the invention may be used in plant transformation or transfection [¶93]. Exogenous genetic material may be transferred into a plant cell and the plant cell regenerated into a whole, fertile or sterile plant (i.e., a transgenic plant cell comprising a recombinant DNA polynucleotide comprising DNA sequence consisting of a sequence comprising any of SEQ ID NOs: 1-23). As detailed above, given that Kovalic teaches a sequence with 100% identity to SEQ ID NO: 20 of the instant application and suggests isolating a regulatory region from the disclosed sequences, and Bernardes teaches motivation for isolating 3’ UTRs other than those traditionally used, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to further transform a plant with the DNA polynucleotide comprising a DNA sequence of SEQ ID NO: 20 operably linked to a heterologous transcribable DNA polynucleotide, which are provided in Kovalic for advances in agricultural plant traits (i.e., wherein the DNA sequence is operably linked to a heterologous transcribable DNA polynucleotide).
Regarding claims 10-11, Kovalic teaches that genetic material may be transferred into either monocotyledons and dicotyledons including, but not limited to maize, soybean, Arabidopsis, phaseolus, peanut, alfalfa, wheat, rice, oat, sorghum, rye, tritordeum, millet, fescue, perennial ryegrass, sugarcane, cranberry, papaya, banana, banana, muskmelon, apple, cucumber, dendrobium, gladiolus, chrysanthemum, liliacea, cotton, eucalyptus, sunflower, canola, turfgrass, sugarbeet, coffee and Dioscorea (i.e., wherein the transgenic plant cell is a dicotyledonous plant cell; wherein the transgenic plant cell is a monocotyledonous plant cell) [¶94].
Regarding claims 12-17, Kovalic teaches that the development or regeneration of plants containing the foreign exogenous genes is well known in the art and that the regenerated plants may be self-pollinated to provide further transgenic plants that are homozygous for the foreign gene (i.e., a transgenic plant or part thereof comprising the recombinant DNA polynucleotide; a progeny plant of the transgenic plant of claim 12, or part thereof, wherein the progeny plant or part thereof comprises the recombinant DNA polynucleotide) [¶129]. Further, Kovalic teaches that a homozygous transgenic plant can be obtained by sexually mating (selfing) an independent segregant transgenic plant that contains a single added gene, germinating some of the seed produced and analyzing the resulting plants produced for the gene of interest (i.e., a transgenic seed, wherein the seed comprises the recombinant DNA polynucleotide; a method of expressing a transcribable DNA polynucleotide comprising obtaining a transgenic plant according to claim 12 and cultivating said plant, wherein the transcribable DNA polynucleotide is expressed) [¶121]. Seeds comprising the material derived from the transgenic plant, as taught by Kovalic, is taken to read on the commodity product (i.e., a method of producing a commodity product comprising obtaining a transgenic plant or part thereof and producing the commodity product therefrom; wherein the commodity product is selected from the group consisting of seeds).
Thus, Kovalic in view of La Rosa, NCBI Reference Sequence: XM_028384730.1, and Bernardes renders obvious claims 1-17.
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 1-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 13 of copending provisional Application No. 19/474,609 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the subject matter claimed in the instant application is disclosed in the referenced patent, and the referenced patent and the instant application are claiming common subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are drawn to a recombinant DNA polynucleotide comprising a DNA sequence consisting of a sequence with at least 85% sequence identity to any of SEQ ID NOs: 1-23, a sequence comprising any of SEQ ID NOs: 1-23, and a fragment of any of SEQ ID NOs: 1-23, wherein the fragment comprises gene regulatory activity and said DNA sequence is operably linked to a heterologous transcribable DNA polynucleotide. Conflicting claim 13 is drawn to a recombinant construct comprising a nucleotide coding sequence operably linked to a heterologous promoter, wherein the heterologous promoter (i.e., gene regulatory activity) comprising a nucleotide sequence that is at least 85% identical to SEQ ID NO: 22. The instant and conflicting applications have identical sequences for SEQ ID NO: 22.
Regarding the instant dependent claims 5-8 and 13-17 and the transgenic plant cell comprising a recombinant DNA polynucleotide comprising any of SEQ ID NOs: 1-23 recited in claims 9-11, with regard to the above 103 rejection (Kovalic and La Rosa) the claims are deemed obvious. Kovalic teaches the limitations of claims 5, 8-17 while La Rosa teaches the limitations of claims 6-7. Although Kovalic and La Rosa do not explicitly teach SEQ ID NO: 22, the use of a heterologous transcribable DNA polynucleotide and operable linkage to a regulatory element was well known in the art at the time of filing, as taught by La Rosa, as was the use of a recombinant DNA polynucleotide conferring a gene of agronomic interest in a transgenic plant cell for the production of a transgenic plant and method of producing a commodity product comprising the transgenic plant, as taught by Kovalic. As copending Patent Application No. 19/474,609 teaches SEQ ID NO: 22 in a recombinant DNA polynucleotide with gene regulatory activity and linked to a heterologous transcribable DNA polynucleotide, the combined references render obvious the instant invention.
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to use SEQ ID NO: 22 of 19/474,609 as it was already used in a recombinant DNA polynucleotide with regulatory gene activity. One would be motivated use this sequence as a gene regulatory element as 19/474,609 indicates that it is a heterologous promoter fragment. One would have reasonable expectation of success given that the methodology of the remaining claim limitations was well known, as demonstrated by La Rosa and Kovalic. Thus, the dependent claims 5-17 are included in the non-statutory rejection of independent claim 1.
Conclusion
No claims allowed.
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/EMILY K JOHNSON/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662
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