DETAILED ACTION
The Examiner provides emphasis by underlining specific parts of quoted and unquoted text herein.
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
The Examiner acknowledges Applicant’s description of “Group I [as consisting of] claims 1-4, 6-9, 12-13, and 17, [which are] drawn to a plant, or a plant cell thereof, with increased phosphorus use efficiency or tolerance to phosphorus deficiency” (Remarks received on 2026-05-21, page 8). The Examiner also acknowledges that “Applicant provisionally elects [said] Group I…without traverse” (Remarks, page 9).
Regarding species election, the Examiner acknowledges that “[s]ince Applicant has elected Group I, Applicant provisionally elects, without traverse, for search purposes: SEQ ID NO: 1 (amino acid sequence) as set forth in claim 1, and SEQ ID NO: 2 (corresponding nucleotide sequence) as set forth in claim 2, and SEQ ID NO: 23 (amino acid sequence) as set forth in claim 6” (Remarks, bridging page 9-10).
Claims 18-19, 25-26, 29-32, and 36-42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
Acknowledgment is made of applicant’s claim for priority to U.S. Provisional Application No. 63362155, filed 2022-03-30. The effective filing date is 2022-03-30.
Status of the Claims
Amendments and election dated 2026-05-21 are entered.
Claims 1-4, 6-9, 12-13, 17-19, 25-26, 29-32, and 36-42 are pending.
Claims 18-19, 25-26, 29-32, and 36-42 are withdrawn for being directed to non-elected invention(s).
Claims 1-4, 6-9, 12-13, and 17 are examined herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2025-03-17 is acknowledged and is being considered by the examiner.
Specification
The specification is objected to because of the following:
Refers to the wrong figures (e.g., “the MYB49 binding motif in ARSK1 promoter displays differential methylation across Arabidopsis accessions (FIG. 4E), and accessions harboring a methylated MYB49 binding motif display low ARSK1 expression (FIG. 4F)” in Specification para 0097 where the referenced figures to not display the recited findings.)
Claim Interpretations
Regarding claims 1-4, 6-9, 12-13, and 17, the “genomic sequence encoding a protein kinase” recited in claim 1 is being given the broadest reasonable interpretation of comprising: transcription regulatory regions like a promoter and 5’ UTR, and a polynucleotide encoding a protein kinase.
Regarding claims 1-4, 6-9, 12-13, and 17, para 0029 of the Specification recites that a “transcription regulatory element” or a “regulatory element” “generally refers to a transcriptional regulatory element involved in regulating the transcription of a nucleic acid molecule such as a gene or a target gene” (emphasis provided).
Regarding claims 1-4, 6-9, 13, and 17, Applicant does not define modification. Specification para 0006 recites that “the genomic modification can be a deletion, insertion, or substitution of nucleotides in a genomic sequence encoding a protein kinase, wherein the modification increases expression or activity of the protein kinase” (emphasis provided).
Regarding claim 6, SEQ ID NO: 23 is listed with alternative amino acid residues on page 46 of the specification.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1-4, 6rejected 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 regards as the invention. All dependent claims are included in these rejections unless they contain a limitation that overcomes the deficiencies of the parent claim from which they depend. Details are listed below.
Claim 1 lacks a comparative basis for the phrase “increased expression or activity of the protein kinase”. Increased compared to any other plant? algae? ubiquitin expression in the instantly claimed plant?
In the interest of compact prosecution, the claims are given the broadest reasonable interpretation of reciting wherein the modification results in increased expression or activity of the protein kinase compared to a corresponding control plant without the modification.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 6 depends from claim 1 with the additional limitation that the protein kinase, recited in claim 1, comprises the amino acid sequence set forth in SEQ ID NO: 23. Claim 1 recites a protein kinase having at least 99% sequence identity with to the amino acid sequence set forth in SEQ ID NO: 1. SEQ ID NO: 23 is only has 98% sequence identity to SEQ ID NO: 1 (see alignment below). This does not meet the 99% threshold recited in claim 1.
RESULT 1
US-18-850-364-1
Query Match 96.0%; Score 254.5; DB 1; Length 424;
Best Local Similarity 98.0%;
Matches 49; Conservative 0; Mismatches 0; Indels 1; Gaps 1;
Qy 1 SDFGL-KDGPEGEHTHVTTRVMGTQGYAAPEYIMTGHLTTMNDVYSFGVV 49
||||| ||||||||||||||||||||||||||||||||||||||||||||
Db 235 SDFGLAKDGPEGEHTHVTTRVMGTQGYAAPEYIMTGHLTTMNDVYSFGVV 284
Thus, claim 6 does not further limit claim 1, as the sequence of SEQ ID NO: 23 is not included SEQ ID NO: 1 as recited in claim 1. Claim 6 fails the infringement test because claim 6 would conceivably be infringed by other sequences, which would not infringe preceding claim 1. See MPEP § 608.01(n).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)
Written description
The following is a quotation of the first paragraph of 35 U.S.C. 112(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.
Claim 13 is 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. All dependent claims are included in these rejections unless they contain a limitation that overcomes the deficiencies of the parent claim from which they depend. Details are listed below.
Applicant discloses:
In Specification para 0096 that “Root growth assays revealed that arsk1 mutant plants display significantly stronger inhibition of root length by −P than wild-type Col-0 plants (FIG. 3E) [while] ARSK1 overexpression prevents root growth inhibition by −P (FIG. 3E).”
in figure 4H that the “Methylation profile in the chromosome 2, 11196502 to 11196862 of Col in response to 9 h of P deficiency” and highlights increased methylation at a cysteine nucleotide within MYB49 motif (i.e., “regulatory element”).
Specification para 0097 that “the MYB49 binding motif in ARSK1 promoter displays differential methylation across Arabidopsis accessions (FIG. 4E), and accessions harboring a methylated MYB49 binding motif display low ARSK1 expression (FIG. 4F)” ( note that Applicant is referring to the wrong figures.)
Regarding modification, Applicant discloses:
In figure 4I the “Transactivation of native and mutated (C->A) ARSK1 promoter:GUS activity after coexpression with MYB49 transcription factor.”
In Specification para 0097 that “To assess whether P-dependent differential methylation in the promoter of ARSK1 affects the binding of MYB49, in planta transactivation assays in Arabidopsis protoplasts were performed using different versions of ARSK1 promoter that drive the expression of the firefly luciferase gene, methylated or mutated at the cytosine residues which influence MYB49 binding were used in these experiments [where] the results revealed luminescence detected only using the native promoter, but not the mutated version of the ARSK1 promoter” and then summarizes that “collectively, the data provide evidence for P limitation-induced DNA methylation of the ASKR1 promoter, which led to downregulation of ARSK1 gene expression.”
Applicant does not disclose a plant where a modification that disrupts a methylation site within a transcription regulatory region in at least one genomic sequence encoding a protein kinase having at least 80% sequence identity to SEQ ID NO: 1 results in increased expression or activity of the protein kinase. And yet, Applicant claims a plant with increased phosphorus use efficiency or tolerance to phosphorus deficiency wherein the plant comprises a modification that disrupts a methylation site within a transcription regulatory region in at least one genomic sequence encoding a protein kinase having at least 80% sequence identity to SEQ ID NO: 1 and wherein the modification results in increased expression or activity of the protein kinase.
Disclosing that overexpression of ASKR1 prevents root growth inhibition, evidence that DNA methylation of the ASKR1 promoter led to downregulation of ARSK1 gene expression, increased methylation at a cysteine nucleotide within the MYB49 binding motif in ARSK1 promoter in response to 9 h of P deficiency, and that in in planta transactivation assays in Arabidopsis protoplasts performed with different versions of ARSK1 promoter driving the expression of the firefly luciferase gene revealed luminescence detected only using the native promoter, but not the mutated version (mutated at the cytosine residues which influence MYB49 binding) of the ARSK1 promoter does not demonstrate that the inventor was in possession of a plant with increased phosphorus use efficiency or tolerance to phosphorus deficiency wherein the plant comprises a modification that disrupts a methylation site within a transcription regulatory region in at least one genomic sequence encoding a protein kinase having at least 80% sequence identity to SEQ ID NO: 1 and wherein the modification results in increased expression or activity of the protein kinase.
Applicant has reduced to practice modification of this particular regulatory region, MYB49 binding motif, within the broader regulatory region comprised in the genomic sequence encoding a protein kinase having at least 80% sequence identity to seq id no: 1 wherein the modification resulted in decreased expression or activity of the luciferase indicator protein used compared to the unmutated version (see Specification figure 4I).
Applicant has not reduced to practice modification of any regulatory region within the genomic sequence encoding a protein kinase having at least 80% sequence identity with seq id no: 1, wherein the modification results in increased expression or activity of an indicator protein used, much less, of the protein kinase (see Specification figure 4I).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1(ii)-4, 6-9, 13, and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon including products of nature, or an abstract idea) without significantly more. The claimed invention is directed to a plant bearing a modification of naturally-occurring nucleic acid, that is not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., --U.S.--(June 13, 2013). All dependent claims are included in these rejections unless they contain a limitation that overcomes the deficiencies of the parent claim from which they depend. The rationale for this determination is explained below.
This rejection is made on the basis that genomic modifications, (i.e., modifications to at least one genomic sequence encoding a protein kinase) can include single and multiple nucleotide polymorphisms (S/MNPS), methylation, and demethylation. See claim interpretation above.
The claims are drawn to a plant with increased phosphorus use efficiency or tolerance to phosphorus deficiency wherein the plant comprises a modification in at least one genomic sequence encoding a protein kinase having at least 80% sequence identity to SEQ ID NO: 1 and wherein the modification results in increased expression or activity of the protein kinase; where in the protein kinase is encoded by a polynucleotide having at least 80% identity to SEQ ID NO: 2; wherein the polynucleotide is operably linked to a promoter function in a plant cell; wherein the promoter is root-preferred; wherein the protein kinase peptide comprises SEQ ID NO: 23; wherein the plant is crop plant; wherein the plant has increased phosphorus use efficiency or tolerance to phosphorus deficiency and increased root biomass compared to the control; and wherein the modification disrupts a methylation site within a transcription regulatory region and a seed from the plant.
SEQ ID NO: 1 and 2 are, respectively, the amino acid sequence of and polynucleotide encoding the Arabidopsis Root Specific Kinase (ARSK1), a naturally occurring gene. The instantly recited genomic sequence encoding a protein kinase having at least 80% sequence identity to SEQ ID NO: 1 appears to be naturally occurring in Arabidopsis and Brassica plants, absent evidence to the contrary.
In naturally occurring plants, the genomic sequence encoding stress-responsive gene ARSK, as with other naturally occurring genes, includes the coding region (i.e., a polynucleotide encoding a protein kinase; see claim interpretations) operably linked to a root-specific promoter functional in a plant cell (henceforth Hwang; Hwang, I. and Goodman, H.M. (1995), An Arabidopsis thaliana root-specific kinase homolog is induced by dehydration, ABA, and NaCl. The Plant Journal, 8: 37-43. https://doi.org/10.1046/j.1365-313X.1995.08010037.x, Published 1995). It is known in the art, as reviewed in 2015 by Vriet (Vriet C, et al. Stress-induced chromatin changes in plants: of memories, metabolites and crop improvement. Cell Mol Life Sci. 2015 Apr;72(7):1261-73. doi: 10.1007/s00018-014-1792-z. Epub 2015 Jan 13. PMID: 25578097; PMCID: PMC11113909.), that stress-responsive genes can undergo “changes in DNA methylation,” DNA methylation and demethylation, that “influence the stress-mediated transcriptional response” where these changes can also be inherited by seeds from this plant (page 1262, col 1, first full para; entire paper). For example, Vriet teaches that “both the demethylation level and the activity of stress-responsive genes were higher in the salt-tolerant than in the salt-sensitive cultivars analyzed” (emphasis provided; para bridging page 1262-1263).
Alternatively, Sato (Hikaru Sato et al. Combinations of maternal-specific repressive epigenetic marks in the endosperm control seed dormancy. bioRxiv 2020.11.10.376806; doi: https://doi.org/10.1101/2020.11.10.376806, published 2020) teaches, in the abstract and figure 5- figure supplement 3, the H3K27me3 demethylase REF and a “list of downregulated genes with single H3K27me3 and REF6-binding sites that were downregulated in ref6-1” mutant plants which includes ARSK1 with a Log2FC of -1.9 (see the figure). In the very same figure and corresponding caption, Sato also teaches that the ARSK1 gene has already been identified as being induced during germination. Germination is considered a form of physiological and metabolic stress because transitioning from a dry, dormant state to a highly active, growing embryo involves rapid water uptake, intense cell division, and a sudden surge in damaging free radicals.
Thus, a plant comprising a genomic sequence encoding a protein kinase having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1 (ARSK1) where the genomic sequence encoding includes transcription regulatory regions like the promoter and 5’ UTR, and the genomic sequence is subject to modification like DNA methylation and DNA demethylation, under stress conditions, including phosphorus deficiency and germination, wherein demethylation of the transcription regulatory region (H3K27me3 site) disrupts a methylation site exist in nature. Further, DNA demethylation of a genomic region is known to relieve methylation-based suppression of genes in that region such that DNA demethylation of the genomic region encoding ARSK1 results in increased expression or activity of the ARSK1.
Regarding claims 8 and 9, as a matter of scientific principle and established patent law, a gene's structure dictates its function (i.e., structure reads on function). The instantly claimed functional properties and characteristics, are inherently present in the naturally occurring plant so long as there is increased expression or activity of the ARSK protein kinase or a protein kinase having at least 80% sequence identity to the amino acid sequence for the stress responsive genes set forth in SEQ ID NO: 1 as recited by Applicant. Since the Patent Office does not have the facilities to examine and compare the plant of Applicant’s with that of a naturally occurring plant having undergone DNA methylation, demethylation, acetylation, the burden of proof is upon the Applicant to show an unobvious distinction between the claimed plant and the plant of the prior art. See In re Best, 562F.2d 1252, 195 USPQ 430 (CCPA 1977).
The claimed plant containing a modification in at least one genomic sequence, and having the inherent properties that are recited in the claims is indistinguishable from a naturally occurring plant, the naturally occurring genomic sequence therein, and the naturally occurring process of demethylation the genomic sequence is naturally subject to. The claimed invention does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed invention is directed to naturally-occurring process(es), genes, cells, and organisms, with naturally occurring gene.. The judicial exception is not integrated into a practical application because the claimed invention is directed to naturally-occurring gene and processes. A claim that focuses on use of a natural principle must also include additional elements or steps to show that the inventor has practically applied, or added something significant to, the natural principle itself. Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. __, 132 S.Ct. 1289,101 USPQ2d 1961 (2012), at 1966. To show integration, the additional elements or steps must relate to the natural principle in a significant way to impose a meaningful limit on the claim scope.
Thus, the claimed products are not patent-eligible pursuant to the Supreme Court decision in Ass'n. for Molecular Pathology v. Myriad Genetics (formerly v. USPTO), 653 F.3d 1329, 99 USPQ2d 1398 (Fed. Cir. 2011), cert. granted, judgment vacated and remanded to the Court of Appeals for the Federal Circuit, No. 11-725, 80 U.S.L.W. 3380, 2012 BL 72224 (U.S. Mar. 26, 2012), reversed, ---- S.Ct. ----, 106 USPQ2d 1972, 1974-75 (2013). The claimed invention does not rise to a level that is markedly different in structure from what exists in nature. See “The 2019 Revised Patent Subject Matter Eligibility Guidance”, issued January 7, 2019, available from the USPTO website at https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 6-9, 12, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Alexandrov (U.S. Patent Application Publication No. 20060150283A1, assigned to Nickolai Alexandrov and Vyacheslav Brover, titled 'Sequence-determined DNA fragments and corresponding polypeptides encoded thereby', published 2006). Details are listed below.
This rejection is made on the basis that Phosphorus is a nutrient and one that is typically included in fertilizers and is a part of the metabolic activities of a plant.
Alexandrov, in the field of molecular genetics, teaches that “polynucleotides, both endogenous polynucleotides and created [i.e., modified] variants, polypeptides, cells, and whole organisms, can be exploited to engineer old and new plant traits” (para 0007), wherein the traits or utility of the “Phenotype Modulated by a Gene” include but are not limited to:
“increasing or decreasing plant biomass, optimizing plant stature to increase yield under various diverse environmental conditions, e.g., when water or nutrients are limiting”, (table bridging pages 39-42, row 21-22)
“increase metabolic efficiency” (row 33)
“increase[d] root biomass,” “control on the depth of root growth in soil to access water and nutriennts” (row 39)
Thus, Alexandrov teaches of “a plant or plant cell thereof with increased phosphorus efficiency or tolerance to phosphorus deficiency” (c.f., claim 1 preamble).
Alexandrov teaches and claims SEQ ID NO: 97386, a polynucleotide which has 100% sequence identity to the nucleotide sequence set forth in instant SEQ ID NO: 2 and encodes the protein kinase polypeptide sequence set forth in SEQ ID NO: 97387 (Alexandrov claim 1) (data/alignment not shown). Alexandrov’s SEQ ID NO: 97387, claimed in Alexandrov’s claim 11, is a sequence for a protein kinase polypeptide which has at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1 see snippet below). Thus, SEQ ID NO: 97386 is a “polynucleotide encoding a protein kinase having at least… 99% sequence identity to at least one of the amino acid sequences set forth in SEQ ID NOs: 1” (c.f., instant claim 1).
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Alexandrov teaches and claims “A plant or cell of a plant which comprises a nucleic acid molecule according to claim 1 which is exogenous or heterologous to said plant or plant cell” (i.e., claim 1 alternative (i): where in the plant comprises a heterologous polynucleotide encoding a protein kinase having at least 99% identity to SEQ ID NO: 1) (Alexandrov claim 15).
Regarding claim 1 alternative (ii), Alexandrov teaches “III.B. Enhanced Expression,” “III.B.2. Regulatory Sequence Modulation,” and “duplication of enhancer elements” (paras 0712, 0714, and
Regarding claim 2, Alexandrov’s SEQ ID NO: 97386 encodes SEQ ID NO: 97387, making it equivalent to “the polynucleotide encoding the protein kinase has at least… 99% sequence identity to at least one of the nucleotide sequences set forth in SEQ ID NO: 2” (c.f., instant claim 2).
Regarding claims 3 and 4, Alexandrov teaches that the “coding region from [Alexandrov’s SEQ ID NO: 97386] might be operably linked to a promoter that is functional in a plant” (para 0099) where the promoter is “a constitutive promoter permitting expression in any cell in a host organism or a promoter that directs transcription only in particular cells or times during a host cell life cycle or in response to environmental stimuli” (para 0717).
Regarding claim 7, Alexandrov teaches that “polynucleotides, both endogenous polynucleotides and created [i.e., modified] variants, polypeptides, cells, and whole organisms, can be exploited to engineer… a vast range of… plants” (para 0007) “including species from the genera..., Brassica, …Glycine [soybean], Gossypium [cotton], …Solanum [potato], Triticum [wheat],…and, Zea [maize]“ (c.f., instant claim 7)(para 0750.
Regarding claims 8 and 9, as a matter of scientific principle and established patent law, a gene's structure inherently dictates its function (i.e., structure reads on function). Because the prior art teaches the exact same coding region (Alexandrov’s SEQ ID NO: 97386 shares 100% identity with instant SEQ ID NO: 2), the instantly claimed functional properties and characteristics, are inherently present in the prior art plant. Accordingly, the claimed invention is anticipated by, or in the alternative, is obvious in view of the prior art. Since the Patent Office does not have the facilities to examine and compare the plant of Applicant’s with that of the prior art, the burden of proof is upon the Applicant to show an unobvious distinction between the claimed plant and the plant of the prior art. See In re Best, 562F.2d 1252, 195 USPQ 430 (CCPA 1977).
Regarding claim 12, Alexandrov specifically teaches that “duplication of enhancer elements or insertion of exogenous enhancer elements increases expression of a desired gene from a particular promoter” (i.e., instant claim 12, wherein the modification comprises an insertion of one or more nucleotides in a transcription regulatory region of the genomic sequence) (para 0878-0879).
Regarding claim 17, Alexandrov teaches that “subsequently produced (T1) seed [are] collected” (para 1269).
Thus, the claimed inventions are anticipated by Alexandrov.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-4, 7-9, 12-13, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Heuer (Heuer, S., et al. 2017. Improving phosphorus use efficiency: a complex trait with emerging opportunities. Plant J, 90: 868-885. https://doi.org/10.1111/tpj.13423, published 2017), Gallego-Bartolomé (J. Gallego-Bartolomé, et al., Targeted DNA demethylation of the Arabidopsis genome using the human TET1 catalytic domain, Proc. Natl. Acad. Sci. U.S.A. 115 (9) E2125-E2134, https://doi.org/10.1073/pnas.1716945115 (2018), published 2018) and Alexandrov (U.S. Patent Application Publication No. 20060150283A1, assigned to Nickolai Alexandrov and Vyacheslav Brover, titled 'Sequence-determined DNA fragments and corresponding polypeptides encoded thereby', published 2006). Details are listed below.
Heuer teaches “the importance of root traits and metabolic changes” in “approaches aiming at the development of crops with enhanced PUE [Phosphorus-use efficiency]” (i.e., plants with increased phosphorus use efficiency) (page 880, col 2, last full para) where “genes… such as [Protein Kinase] CIPK23 [and serine/threonine kinase OsPSTOL1], hold promise and provide first entry points for optimizing root growth in crops” (page 872, col 1, first full para).
Heuer does not explicitly teach a heterologous polynucleotide encoding a protein kinase having at least 99% sequence identity to at least one of the amino acid sequence set forth in SEQ ID NO: 1 or a modification in at least one genomic sequence encoding a protein kinase having at least 99% sequence identity to at least one of the amino acid sequence set forth in SEQ ID NO: 1, and wherein the modification results in increased expression or activity of the protein kinase.
Gallego-Bartolomé, in the field of molecular genetics, teaches modification of plant genomic DNA in a targeted manner regarding “DNA methylation[,] an epigenetic modification” where DNA demethylation of the promoter region of a gene led to increased expression of the encoded protein(i.e., modification of a genomic sequence) (Abstract; entire paper).
Alexandrov, also in the field of molecular genetics, teaches and claims SEQ ID NO: 97386, a polynucleotide which has 100% sequence identity to the nucleotide sequence set forth in SEQ ID NO: 2 and encodes the protein kinase polypeptide sequence set forth in SEQ ID NO: 97387 (Alexandrov claim 1)(data not shown). Alexandrov’s SEQ ID NO: 97387, claimed in Alexandrov’s claim 11, is a sequence for a protein kinase polypeptide which has at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1 see snippet below). Thus, SEQ ID NO: 97386 is a polynucleotide or a genomic sequence encoding a protein kinase having at least 99% sequence identity to at least one of the amino acid sequences set forth in SEQ ID NOs: 1 (c.f., instant claim 1), and the polynucleotide encoding the protein kinase has at least 99% sequence identity to at least one of the nucleotide sequences set forth in SEQ ID NO: 2 (c.f., instant claim 2).
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Alexandrov, teaches that “polynucleotides, both endogenous polynucleotides and created [i.e., modified] variants, polypeptides, cells, and whole organisms, can be exploited to engineer old and new plant traits” (para 0007), wherein the traits or utility of the “Phenotype Modulated by a Gene” include but are not limited to:
“increasing or decreasing plant biomass, optimizing plant stature to increase yield under various diverse environmental conditions, e.g., when water or nutrients are limiting”, (table bridging pages 39-42, row 21-22)
“increase metabolic efficiency” (row 33)
“increase[d] root biomass,” “control on the depth of root growth in soil to access water and nutrients” (row 39)
Alexandrov also teaches that “PARSK1, the promoter from the Arabidopsis gene encoding a serine-threonine kinase enzyme, and which promoter is induced by dehydration, abscissic acid and sodium chloride. One of ordinary skill in the art would take an interest in the protein kinase encoded by the gene with the promoter PARSK1 and motivated to find homologs and orthologs using BLAST would be able to identify Alexandrov’s SEQ ID NO: 97387 as the ARSK1 protein kinase.
Thus, Alexandrov teaches of “a plant or plant cell thereof with increased phosphorus efficiency or tolerance to phosphorus deficiency” (c.f., instant claim 1 preamble).
Alexandrov also claims “A plant or cell of a plant which comprises a nucleic acid molecule according to claim 1 which is exogenous or heterologous to said plant or plant cell” (i.e., claim 1 alternative (i): where in the plant comprises a heterologous polynucleotide encoding a protein kinase having at least 99% identity to SEQ ID NO: 1)(Alexandrov claim 15).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined teachings of Heuer (root traits) and Alexandrov (SEQ ID NO: 97386 and heterologous expression) with the demethylation (i.e., modification of genomic sequences encoding protein kinases that are induced by abiotic stresses) teachings of Gallego-Bartolomé, arriving at the claimed inventions with a reasonable expectation of success and no surprising results. One would have been motivated to do this in order to “activat[e] genes normally silenced by DNA methylation [or] previously silenced transgenes” (Gallego-Bartolomé, page e2132, col 2, third full para) or express them exogenously.
Regarding claims 3 and 4, Alexandrov teaches that the “coding region from [Alexandrov’s SEQ ID NO: 97386] might be operably linked to a promoter that is functional in a plant” (para 0099) where the promoter is “a constitutive promoter permitting expression in any cell in a host organism or a promoter that directs transcription only in particular cells or times during a host cell life cycle or in response to environmental stimuli” (para 0717).
Regarding claim 7, Alexandrov also teaches that “polynucleotides, both endogenous polynucleotides and created [i.e., modified] variants, polypeptides, cells, and whole organisms, can be exploited to engineer old and new plant traits in a vast range of… plants” (para 0007) “including species from the genera..., Brassica, …Glycine [soybean], Gossypium [cotton], …Solanum [potato], Triticum [wheat],…and, Zea [maize]“ (c.f., instant claim 7)(para 0750), wherein the traits or utility of the “Phenotype Modulated by a Gene” include but are not limited to:
“increasing or decreasing plant biomass, optimizing plant stature to increase yield under various diverse environmental conditions, e.g., when water or nutrients are limiting”, (table bridging pages 39-42, row 21-22)
“increase metabolic efficiency” (row 33)
“increase[d] root biomass,” “control on the depth of root growth in soil to access water and nutrients” (row 39)
Thus, Alexandrov also teaches of a plant or plant cell thereof with increased phosphorus efficiency or tolerance to phosphorus deficiency.
Regarding claims 8 and 9, as a matter of scientific principle and established patent law, a gene's structure inherently dictates its function (i.e., structure reads on function). Because the prior art teaches the exact same coding region (Alexandrov’s SEQ ID NO: 97386 shares 100% identity with instant SEQ ID NO: 2), the instantly claimed functional properties and characteristics, are inherently present in the prior art plant. Accordingly, the claimed invention is anticipated by, or in the alternative, is obvious in view of the prior art. Since the Patent Office does not have the facilities to examine and compare the plant of Applicant’s with that of the prior art, the burden of proof is upon the Applicant to show an unobvious distinction between the claimed plant and the plant of the prior art. See In re Best, 562F.2d 1252, 195 USPQ 430 (CCPA 1977).
Regarding claim 12, Alexandrov specifically teaches that “duplication of enhancer elements or insertion of exogenous enhancer elements increases expression of a desired gene from a particular promoter” (i.e., instant claim 12, wherein the modification comprises an insertion of one or more nucleotides in a transcription regulatory region of the genomic sequence)(para 0878-0879).
Regarding claim 13, Alexandrov teaches that “Genes can include non-coding sequences that modulate [or regulate] the genetic function that include, but are not limited to, those that specify polyadenylation, transcriptional regulation, DNA conformation, chromatin conformation, extent and position of base methylation and binding sites of proteins that control all of these” (para 0762) and then that “enhanced expression of a gene of interest in a host cell is accomplished by either (1) insertion of an exogenous gene; or (2) promoter modulation [i.e., modification in at least one genomic sequence encoding a protein kinase having at least 99% sequence identity to at least one of the amino acid sequences set forth in SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, or 21, and wherein the modification results in increased expression or activity of the protein kinase]” (para 0873) and further teaches “Regulatory Sequence Modulation” (para 0878) such that sequences that regulate the extent or position of a base methylation (i.e., methylation site) are included in regulatory sequences.
Further regarding claim 13, Gallego-Bartolomé explicitly teaches targeted “demethylation of the…promoter” region of genes (i.e., wherein the modification disrupts a methylation site within the transcription regulatory region) (page E2132, col 1, first full para).
Regarding claim 17, Alexandrov teaches that “subsequently produced (T1) seed [are] collected” (para 1269).
Subject Matter Free of Prior art
Regarding instant claim 6, Alexandrov’s claimed SEQ ID NO: 97387, like the amino acid sequence set forth in instant SEQ ID NO: 1, comprises a sequence that shares only 98% identity with the amino acid sequences set forth in SEQ ID NOs: 23 (see alignment below).
RESULT 1
US-11-056-355B-97387
Query Match 96.0%; Score 254.5; DB 1; Length 424;
Best Local Similarity 98.0%;
Matches 49; Conservative 0; Mismatches 0; Indels 1; Gaps 1;
Qy 1 SDFGL-KDGPEGEHTHVTTRVMGTQGYAAPEYIMTGHLTTMNDVYSFGVV 49
||||| ||||||||||||||||||||||||||||||||||||||||||||
Db 235 SDFGLAKDGPEGEHTHVTTRVMGTQGYAAPEYIMTGHLTTMNDVYSFGVV 284
Thus, Alexandrov does not teach the limitations of the instant claim 6.
Conclusion
No claims allowed.
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/YVETTE B. TAMUKONG/ Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/ Supervisory Patent Examiner, Art Units 1661 & 1662
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