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 .
Election/Restrictions
Applicant’s election without traverse of Group I of claims 1-9, and 19-20, in the reply filed on September 04, 2025 is acknowledged. Claims 10-18, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Additionally, Applicant’s species election of SEQ ID NO: 1 in the reply filed on September 04, 2025, is acknowledged.
The restriction is made FINAL.
Claim Status
Claims 1-20, are pending.
Claims 10-18, are withdrawn for being directed to non-elected inventions and not examined on its merits.
Claims 1-9, and 19-20, are examined in the instant application.
Priority
This application is claiming the priority benefit of provisional App# 63/463,338 filed May 02, 2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 10, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Page 47, Paragraph [0197]
www.pdb.org
Appropriate correction is required.
Claim Objections
Claim 20, is objected to because the preamble/claim is missing a verb (“comprises”, “encodes”, etc.); cf. preceding claim 19. In the interest of compact prosecution, the claim is nonetheless examined.
Appropriate correction is required.
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 19-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to a natural phenomenon without conveying a “markedly different” characteristic. As described in MPEP § 2106, subsection III, Step 2A of the Office’s eligibility analysis is the first part of the Alice/Mayo test, i.e., the Supreme Court’s "framework for distinguishing patents that claim laws of nature, natural phenomena, and abstract ideas from those that claim patent-eligible applications of those concepts." Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217-18, 110 USPQ2d 1976, 1981 (2014) (citing Mayo, 566 U.S. at 77-78, 101 USPQ2d at 1967-68).
In regard to claim 19, it is directed to a nucleic acid encoding npr1 (SAL) protein. Therefore, the naturally occurring npr1 nucleic acid is found in nature and not patent-eligible. For example, NCBI et al. (regulatory protein (NPR1) [Arabidopsis thaliana] NCBI Reference Sequence: NP_176610.1. 2022(U)) having 99.49% sequence identity to Applicants SEQ ID NO: 1 is a naturally occurring npr1 protein.
LOCUS NP_176610 593 aa linear PLN 20-OCT-2022
DEFINITION regulatory protein (NPR1) [Arabidopsis thaliana].
ACCESSION NP_176610
VERSION NP_176610.1
DBLINK BioProject: PRJNA116
BioSample: SAMN03081427
DBSOURCE REFSEQ: accession NM_105102.3
KEYWORDS RefSeq.
SOURCE Arabidopsis thaliana (thale cress)
ORGANISM Arabidopsis thaliana
Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae;
Pentapetalae; rosids; malvids; Brassicales; Brassicaceae;
Camelineae; Arabidopsis.
REFERENCE 1 (residues 1 to 593)
AUTHORS Theologis,A., Ecker,J.R., Palm,C.J., Federspiel,N.A., Kaul,S.,
White,O., Alonso,J., Altafi,H., Araujo,R., Bowman,C.L.,
Brooks,S.Y., Buehler,E., Chan,A., Chao,Q., Chen,H., Cheuk,R.F.,
Chin,C.W., Chung,M.K., Conn,L., Conway,A.B., Conway,A.R.,
Creasy,T.H., Dewar,K., Dunn,P., Etgu,P., Feldblyum,T.V., Feng,J.,
Fong,B., Fujii,C.Y., Gill,J.E., Goldsmith,A.D., Haas,B.,
Hansen,N.F., Hughes,B., Huizar,L., Hunter,J.L., Jenkins,J.,
Johnson-Hopson,C., Khan,S., Khaykin,E., Kim,C.J., Koo,H.L.,
Kremenetskaia,I., Kurtz,D.B., Kwan,A., Lam,B., Langin-Hooper,S.,
Lee,A., Lee,J.M., Lenz,C.A., Li,J.H., Li,Y., Lin,X., Liu,S.X.,
Liu,Z.A., Luros,J.S., Maiti,R., Marziali,A., Militscher,J.,
Miranda,M., Nguyen,M., Nierman,W.C., Osborne,B.I., Pai,G.,
Peterson,J., Pham,P.K., Rizzo,M., Rooney,T., Rowley,D., Sakano,H.,
Salzberg,S.L., Schwartz,J.R., Shinn,P., Southwick,A.M., Sun,H.,
Tallon,L.J., Tambunga,G., Toriumi,M.J., Town,C.D., Utterback,T.,
Van Aken,S., Vaysberg,M., Vysotskaia,V.S., Walker,M., Wu,D., Yu,G.,
Fraser,C.M., Venter,J.C. and Davis,R.W.
TITLE Sequence and analysis of chromosome 1 of the plant Arabidopsis
thaliana
JOURNAL Nature 408 (6814), 816-820 (2000)
PUBMED 11130712
REFERENCE 2 (residues 1 to 593)
CONSRTM NCBI Genome Project
TITLE Direct Submission
JOURNAL Submitted (19-OCT-2022) National Center for Biotechnology
Information, NIH, Bethesda, MD 20894, USA
REFERENCE 3 (residues 1 to 593)
AUTHORS Krishnakumar,V., Cheng,C.-Y., Chan,A.P., Schobel,S., Kim,M.,
Ferlanti,E.S., Belyaeva,I., Rosen,B.D., Micklem,G., Miller,J.R.,
Vaughn,M. and Town,C.D.
TITLE Direct Submission
JOURNAL Submitted (18-JUL-2017) Plant Genomics, J. Craig Venter Institute,
9704 Medical Center Dr, Rockville, MD 20850, USA
REMARK Protein update by submitter
REFERENCE 4 (residues 1 to 593)
AUTHORS Krishnakumar,V., Cheng,C.-Y., Chan,A.P., Schobel,S., Kim,M.,
Ferlanti,E.S., Belyaeva,I., Rosen,B.D., Micklem,G., Miller,J.R.,
Vaughn,M. and Town,C.D.
TITLE Direct Submission
JOURNAL Submitted (17-MAY-2016) Plant Genomics, J. Craig Venter Institute,
9704 Medical Center Dr, Rockville, MD 20850, USA
REMARK Protein update by submitter
REFERENCE 5 (residues 1 to 593)
AUTHORS Swarbreck,D., Lamesch,P., Wilks,C. and Huala,E.
CONSRTM TAIR
TITLE Direct Submission
JOURNAL Submitted (18-FEB-2011) Department of Plant Biology, Carnegie
Institution, 260 Panama Street, Stanford, CA, USA
COMMENT REVIEWED REFSEQ: This record has been curated by TAIR and Araport.
The reference sequence is identical to AEE34220.
Method: conceptual translation.
FEATURES Location/Qualifiers
source 1..593
/organism="Arabidopsis thaliana"
/db_xref="taxon:3702"
/chromosome="1"
/ecotype="Columbia"
Protein 1..593
/product="regulatory protein (NPR1)"
/calculated_mol_wt=65901
Region 47..194
/region_name="BTB_POZ_NPR_plant"
/note="BTB (Broad-Complex, Tramtrack and Bric a brac) /POZ
(poxvirus and zinc finger) domain found in plant
regulatory proteins, NPR1-4, and similar proteins;
cd18310"
/db_xref="CDD:349619"
Region 231..271
/region_name="DUF3420"
/note="Domain of unknown function (DUF3420); pfam11900"
/db_xref="CDD:314729"
Region <271..>371
/region_name="ANKYR"
/note="Ankyrin repeat [Signal transduction mechanisms];
COG0666"
/db_xref="CDD:440430"
Region 298..326
/region_name="ANK repeat"
/note="ANK repeat [structural motif]"
/db_xref="CDD:293786"
Region 328..359
/region_name="ANK repeat"
/note="ANK repeat [structural motif]"
/db_xref="CDD:293786"
Region 370..564
/region_name="NPR1_like_C"
/note="NPR1/NIM1 like defence protein C terminal;
pfam12313"
/db_xref="CDD:372037"
CDS 1..593
/gene="NPR1"
/locus_tag="AT1G64280"
/gene_synonym="ARABIDOPSIS NONEXPRESSER OF PR GENES 1;
ATNPR1; F15H21.6; F15H21_6; NIM1; NON-INDUCIBLE IMMUNITY
1; NONEXPRESSER OF PR GENES 1; REGULATORY PROTEIN NPR1;
SAI1; SALICYLIC ACID INSENSITIVE 1"
/coded_by="NM_105102.3:252..2033"
/inference="Similar to RNA sequence,
EST:INSD:EL201365.1,INSD:BP666956.1,INSD:BP598549.1,
INSD:BP622100.1,INSD:BP571537.1,INSD:BP577700.1,
INSD:EH838194.1,INSD:BP571734.1,INSD:EL137225.1,
INSD:AV557971.1,INSD:AV792794.1,INSD:AI997958.1,
INSD:EL235963.1,INSD:AV803934.1,INSD:AV796340.1,
INSD:AV538866.1,INSD:BU636357.1,INSD:EL154260.1,
INSD:EL154331.1,INSD:BP580253.1,INSD:DR750055.1,
INSD:EG528533.1,INSD:BP581315.1,INSD:BP856785.1,
INSD:T22612.1,INSD:AV551266.1,INSD:BP570007.1,
INSD:DR377801.1,INSD:BP566856.1,INSD:BX839797.1,
INSD:BP581392.1,INSD:DR750054.1,INSD:BP868377.1,
INSD:EL286142.1,INSD:BP797190.1,INSD:BP779221.1,
INSD:DR290816.1,INSD:AA395706.1,INSD:DR290817.1,
INSD:BP644819.1,INSD:EG528500.1,INSD:EL054377.1,
INSD:BP824743.1,INSD:BP669451.1,INSD:AV825882.1,
INSD:BP666819.1"
/inference="similar to RNA sequence,
mRNA:INSD:AY088183.1,INSD:AY050455.1,INSD:BX817021.1,
INSD:BX813873.1,INSD:AY093992.1,INSD:BX815924.1,
INSD:U76707.1"
/note="NONEXPRESSER OF PR GENES 1 (NPR1); CONTAINS
InterPro DOMAIN/s: BTB/POZ (InterPro:IPR013069), NPR1/NIM1
like, C-terminal (InterPro:IPR021094), BTB/POZ fold
(InterPro:IPR011333), Ankyrin repeat-containing domain
(InterPro:IPR020683), BTB/POZ-like (InterPro:IPR000210),
Ankyrin repeat (InterPro:IPR002110); BEST Arabidopsis
thaliana protein match is: Ankyrin repeat family protein /
BTB/POZ domain-containing protein (TAIR:AT4G26120.1); Has
5193 Blast hits to 3365 proteins in 257 species: Archae -
2; Bacteria - 309; Metazoa - 2278; Fungi - 110; Plants -
802; Viruses - 16; Other Eukaryotes - 1676 (source: NCBI
BLink)."
/db_xref="Araport:AT1G64280"
/db_xref="GeneID:842733"
/db_xref="TAIR:AT1G64280"
ORIGIN
1 mdttidgfad syeisstsfv atdntdssiv ylaaeqvltg pdvsalqlls nsfesvfdsp
61 ddfysdaklv lsdgrevsfh rcvlsarssf fksalaaakk ekdsnntaav klelkeiakd
121 yevgfdsvvt vlayvyssrv rpppkgvsec adencchvac rpavdfmlev lylafifkip
181 elitlyqrhl ldvvdkvvie dtlvilklan icgkacmkll drckeiivks nvdmvsleks
241 lpeelvkeii drrkelglev pkvkkhvsnv hkaldsddie lvklllkedh tnlddacalh
301 favaycnvkt atdllkldla dvnhrnprgy tvlhvaamrk epqlilslle kgasaseatl
361 egrtalmiak qatmavecnn ipeqckhslk grlcveileq edkreqiprd vppsfavaad
421 elkmtlldle nrvalaqrlf pteaqaamei aemkgtcefi vtslepdrlt gtkrtspgvk
481 iapfrileeh qsrlkalskt velgkrffpr csavldqimn cedltqlacg eddtaekrlq
541 kkqrymeiqe tlkkafsedn lelgnssltd stsstskstg gkrsnrklsh rrr
In regard to claim 20, it is directed to a nucleic acid encoding Arabidopsis npr1 (SAL) protein. Therefore, the naturally occurring npr1 nucleic acid is found in nature and not patent-eligible, (see above).
The claims do 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 nucleic acid(s) and protein(s). The claimed nucleic acids, proteins, and plant(s) have the inherent property/ies that are recited in the claims. The judicial exception is not integrated into a practical application because the claimed invention is directed to naturally-occurring nucleotides, cells, organisms, 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.
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 § 112(a)(Written Description)
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 1-9, and 19-20 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 written description requirement may be satisfied through sufficient description of a representative number of species by disclosing relevant and identifying characteristics such as structural or other physical and/or chemical properties, by disclosing 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 invention as claimed. See Eli Lilly,119 F.3d at 1568, 43 USPQ2d at 1406.
Applicant’s disclosure is as follows.
Applicant genetically modified Arabidopsis and Nicotiana benthamiana with SEQ ID NO: 1 having mutations at positions (Q400C/E401L/R506C), (see page 28 paragraph [0133], figure 1 and page 36 paragraph [0157] and figure 6), to increase gene expression of NPR1 and pathogen resistance against Pseudomonas syringae pv. maculicola ES4326.
Claims encompass any plant comprising any npr1(SAL) variant - in the specification only describes Arabidopsis and Nicotiana benthamiana comprising SEQ ID NO: 1.
The claimed invention lacks adequate written description for the following reasons. Claims 1-9 and 19-20, are directed to genetically modifying any plant species with a nucleic acid encoding the npr1(SAL) protein.
The specification has only described genetically modifying Arabidopsis and Nicotiana benthamiana with SEQ ID NO: 1 having mutations at positions (Q400C/E401L/R506C), resulting in conferring pathogen resistance against Pseudomonas syringae pv. maculicola ES4326. Applicant has provided sequence alignments of other NPR1 proteins, (see figures 9 and 15). However, these structures in the sequence alignment are not adequately described to result in said phenotype, which SEQ ID NO: 1 is the only example to confer said phenotype. Therefore, any other NPR1 protein, structure, or orthologs of NPR1 protein is not described to confer pathogen resistance against Pseudomonas syringae pv. maculicola ES4326. For example, a blast search of the top ten results shows proteins as unnamed, predicted, and hypothetical lacking adequate description of other npr1 proteins.
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Suggesting that a person skilled in the art does not know what is the function of said protein and that other sequences may have different functional roles.
Specifically, In regards to claim 8, where it claims that said npr1 would result in increased growth under any biotic and abiotic stress conditions in all plants. For example, Backer et al. (The NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1) and Related Family: Mechanistic Insights in Plant Disease Resistance. Frontiers in plant science vol. 10 102. 13 Feb. 2019, doi:10.3389/fpls.2019.00102 (V)), describes that “[t]he varied functional role of NPR1-like proteins suggests a complex functionally important family involved in plant immune responses and development.”, (see page 2 left column 3rd paragraph), suggesting many roles under this npr1 gene family. Therefore, one skilled in the art would find it unpredictable if one would express said gene or variants of said gene in a sequoia tree would it also result in increased growth.
As for claim 6, the Applicant claims that only two modified amino acids positions (400C and 506C) are required to produce said phenotype, while positions 401A, 401L, 402A, or 402L are optional and have not been reduced to practice. However, only describes positions 400C, 401L, and 506C are all essential for the observed phenotype, (see specification page 34 paragraph [0150] last sentence). Therefore, to see said phenotype SEQ ID NO: 1 needs these point mutations, which not all variations have said mutations.
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Furthermore, while SEQ ID NO: 1 comprises a total of 593 amino acids, the Applicant fails to describe the remaining 590 positions. Because these positions are relative to the AtNPR1 amino acid SEQ ID NO: 3, the disclosure is incomplete; it does not describe whether these remaining residues must be maintained for structural and functional integrity, or if they can be modified without loss of the claimed phenotype. For example, even a single amino acid substitution can radically alter a protein’s tertiary structure and biological activity, the absence of this description forces a person skilled in the art to engage in undue experimentation to determine which variations would still yield the claimed phenotype.
Additionally, Applicant has not described a representative number from the broad genus of plants comprising SEQ ID NO: 1 resulting in the claimed phenotype. Applicant has not described if other species of plants will also confer pathogen resistance against Pseudomonas syringae pv. maculicola ES4326. The resulting phenotype depends on the specific npr1 gene used, as the NPR1 (SAL) belongs to a gene family with diverse biological roles. Furthermore, the phenotype outcome is influence not only by the specific NPR1 gene but also by the host plant species in which the heterologous gene is being expressed. Backer describes that “NPR1-like proteins in different plant species increases, so does the complexity and variability in function.”, (see page 4 bottom section). Suggesting that the NPR1 gene family has many roles and vary between plant species.
Specifically, Backer describes that “Clade 1 (AtNPR1 and AtNPR2) is involved with positive SAR regulation, clade 2 (AtNPR3 and AtNPR4) with negative SAR regulation and clade 3 (AtBOP1 and AtBOP2) with growth and development of leaves and flowers…. These clades are not always functionally robust and as such phylogenetic analyses alone are insufficient for functional annotation.”, (see page 4 bottom section). This suggests that only through a specific NPR1 gene will it confer the desired phenotype. Therefore, Applicant has only described Arabidopsis and Nicotiana benthamiana plants with SEQ ID NO:1 to arrive at said phenotype, they have not described that any other plant as claimed that can produce said phenotype and any NPR1 (SAL) protein producing a predictable phenotype.
This demonstrates that not all plants as broadly encompassed by the claims have been adequately described to genetically modify with an NPR1 gene and achieve the desired phenotype, further highlighting the unpredictable nature of all NPR1 genes and all plants. Therefore, the specification has not described a representative number of species of plants that genetically modified with an NPR1 protein to yield the claimed trait of increased growth under any biotic and abiotic stress conditions.
Accordingly, there is lack of adequate description to inform a skilled artisan that Applicant was in possession of the claimed invention at the time of filing. See Written Description guidelines published in Federal Register/ Vol.66, No. 4/ Friday, January 5, 2001/ Notices; p. 1099-1111
Claim Rejections - 35 USC § 112(a)(Enablement)
Claims 1-9 and 19-20, are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabled for only genetically modified Arabidopsis and Nicotiana benthamiana with SEQ ID NO: 1 having mutations at positions (Q400C/E401L/R506C), (see page 28 paragraph [0133], figure 1 and page 36 paragraph [0157] and figure 6), to increase gene expression of NPR1 and pathogen resistance against Pseudomonas syringae pv. maculicola ES4326, does not reasonably enable genetically any plant with any npr1 protein having any structure to get said phenotype. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
An “analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.” MPEP 2164.01. “A conclusion of lack of enablement means that. . . the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention [i.e. commensurate scope] without undue experimentation.” In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); MPEP 2164.01.
In in re Wands, 858 F.2d 731,8 USPQ2d 1400 (Fed. Cir. 1988), several factors implicated in determination of whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” are identified. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). No single factor is independently determinative of enablement; rather “[i]t is improper to conclude that a disclosure is not enabling based on an analysis of only one of the above factors while ignoring one or more of the others.” MPEP 2164.01. Likewise, all factors may not be relevant to the enablement analysis of any individual claim.
(A) The breadth of the claims
The claims broadly encompass genetically modifying any plant with any NPR1 (SAL) protein. However, Applicant has only taught only genetically modified Arabidopsis and Nicotiana benthamiana with SEQ ID NO: 1 having mutations at positions (Q400C/E401L/R506C), (see page 28 paragraph [0133], figure 1 and page 36 paragraph [0157] and figure 6), to increase gene expression of NPR1 and pathogen resistance against Pseudomonas syringae pv. maculicola ES4326.
(B) The nature of the invention.
The nature of the claimed invention is directed to any plant being genetically modified with NPR1(SAL) protein, resulting in the plant conferring pathogen resistance against Pseudomonas syringae pv. maculicola ES4326. The specification is not enabled for any plant and any NPR1 gene having any structure or function.
(C) The state of the prior art, (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The claimed invention lacks adequate enabling guidance for the following reasons. Claims 1-9, and 19-20, are directed to genetically modifying any plant species with a nucleic acid encoding the npr1(SAL) protein resulting in increased growth under any biotic and abiotic stress conditions.
The specification has only provided enabling guidance on genetically modifying Arabidopsis and Nicotiana benthamiana with SEQ ID NO: 1 having mutations at positions (Q400C/E401L/R506C), resulting in conferring pathogen resistance against Pseudomonas syringae pv. maculicola ES4326. Applicant has provided sequence alignments of other NPR1 proteins, (see figures 9 and 15). However, these structures in the sequence alignment are not adequately enabled to result in said phenotype, which SEQ ID NO: 1 is the only example to confer said phenotype. Therefore, any other NPR1 protein, structure, or orthologs of NPR1 protein is not enabled to confer pathogen resistance against Pseudomonas syringae pv. maculicola ES4326. For example, a blast search of the top ten results shows proteins as unnamed, predicted, and hypothetical lacking adequate enabling guidance of SEQ ID NO: 1 and/or other npr1 proteins.
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Suggesting that a person skilled in the art does not know what is the function of said protein and that other sequences may have different functional roles.
Specifically, In regards to claim 8, where it claims that said npr1 would result in increased growth under any biotic and abiotic stress conditions in all plants. For example, Backer et al. (The NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1) and Related Family: Mechanistic Insights in Plant Disease Resistance. Frontiers in plant science vol. 10 102. 13 Feb. 2019, doi:10.3389/fpls.2019.00102 (V)), teaches that “[t]he varied functional role of NPR1-like proteins suggests a complex functionally important family involved in plant immune responses and development.”, (see page 2 left column 3rd paragraph). Therefore, one skilled in the art would find it unpredictable if one would express said gene in a sequoia tree would it also result in increased growth. Therefore, one skilled in the art would find it unpredictable if one would express said gene or variants of said gene in a sequoia tree would it also result in increased growth.
As for claim 6, the Applicant claims that only two modified amino acids positions (400C and 506C) are required to produce said phenotype, while positions 401A, 401L, 402A, or 402L are optional and have not been reduced to practice. However, only provides enabling guidance for positions 400C, 401L, and 506C are all essential for the observed phenotype, (see specification page 34 paragraph [0150] last sentence). Therefore, to see said phenotype SEQ ID NO: 1 needs these point mutations, which not all variations have said mutations.
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Greyscale
Furthermore, while SEQ ID NO: 1 comprises a total of 593 amino acids, the Applicant fails to enable the remaining 590 positions. Because these positions are relative to the AtNPR1 amino acid SEQ ID NO: 3, the disclosure is incomplete; it does not enable whether these remaining residues must be maintained for structural and functional integrity, or if they can be modified without loss of the claimed phenotype. For example, even a single amino acid substitution can radically alter a protein’s tertiary structure and biological activity, the absence of this enabling guidance forces a person skilled in the art to engage in undue experimentation to determine which variations would still yield the claimed phenotype.
Additionally, Applicant has not enabled a representative number from the broad genus of plants comprising SEQ ID NO: 1 resulting in the claimed phenotype. Applicant has not taught if other species of plants will also confer pathogen resistance against Pseudomonas syringae pv. maculicola ES4326. The resulting phenotype depends on the specific npr1 gene used, as the NPR1 (SAL) belongs to a gene family with diverse biological roles. Furthermore, the phenotype outcome is influence not only by the specific NPR1 gene but also by the host plant species in which the heterologous gene is being expressed. Backer describes that “NPR1-like proteins in different plant species increases, so does the complexity and variability in function.”, (see page 4 bottom section). Suggesting that the NPR1 gene family has many roles and vary between plant species.
Specifically, Backer teaches that “Clade 1 (AtNPR1 and AtNPR2) is involved with positive SAR regulation, clade 2 (AtNPR3 and AtNPR4) with negative SAR regulation and clade 3 (AtBOP1 and AtBOP2) with growth and development of leaves and flowers…. These clades are not always functionally robust and as such phylogenetic analyses alone are insufficient for functional annotation.”, (see page 4 bottom section). This suggests that only through a specific NPR1 gene will it confer the desired phenotype. Therefore, Applicant has only enabled Arabidopsis and Nicotiana benthamiana plants with SEQ ID NO:1 to arrive at said phenotype, they have not enabled that any other plant as claimed that can produce said phenotype and any NPR1 (SAL) protein producing a predictable phenotype.
This demonstrates that not all plants as broadly encompassed by the claims have been adequately enabled to genetically modify with an NPR1 gene and achieve the desired phenotype, further highlighting the unpredictable nature of all NPR1 genes and all plants. Therefore, the specification has not enabled a representative number of species of plants that genetically modified with an NPR1 protein to yield the claimed trait of increased growth under any biotic and abiotic stress conditions.
Given the breadth of the claims, the lack of sufficient guidance, the absence of working examples with all plants comprising any gene scope, the state of the prior art, and unpredictability in the art, one skilled in the art cannot make and use the claimed invention as commensurate in scope with the claims without excessive burden and undue experimentation.
For at least this reason, the Specification does not teach a person with skill in the art how to make and/or use the subject matter within the full scope of these Claims.
Claim Rejections - 35 USC § 112(b)(Indefinite)
Claim 9 is 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.
Regarding claim 9, the phrase "similar" (plant) renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "similar"), thereby rendering the scope of the claim(s) unascertainable. What is the plant similar in appearance? in genus? In species? in age? In genotype? what is similar? it is unknow how to compare? See MPEP § 2173.05(d).
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 1-5, 8-9, and 19-20, are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dong et al. ( US 2002/0138872 A1 (A)).
Regarding claim 1 only requires genetically modify any plant with any nucleic acid encoding a NPR1(SAL) protein. In regard to claim 1, Dong discloses transforming plants with npr1 (i.e. genetically modifying a plant with npr1 (SAL) protein), (see page 13 paragraph [0132] and figure 2b).
Further regarding claims 2-5 and 19-20, Dong discloses “[i]n one working example, constitutive ectopic expression of the NPR1 gene of Arabidopsis (FIG. 5; SEQ ID NO:2) or the NPR1 homolog of Nicotiana glutinosa (FIG. 7A; SEQ ID NO:13) in Russet Burbank potato is used to control Phytophthora infestans infection” (i.e. heterologous nucleic acid encoding the npr1(SAL) protein) and (Arabidopsis npr1(SAL))(i.e. derived from the same species), (see paragraph [0225]). Additionally, Dong’s nucleic acid sequence SEQ ID NO: 2 encodes the amino acid sequence SEQ ID NO: 3, having 99.2% sequence identity to Applicants SEQ ID NO: 1, which is an ortholog of an Arabidopsis npr1(SAL), which also reads on claim 4 section (a), (see alignment below).
RESULT 2
US-08-908-884-3
(NOTE: this sequence has 37 duplicates in the database searched)
Sequence 3, US/08908884
Publication No. US20020138872A1
GENERAL INFORMATION
APPLICANT: Dong et al.
TITLE OF INVENTION: ACQUIRED RESISTANCE GENES AND USES THEREOF
CURRENT APPLICATION NUMBER: US/08/908,884
PRIOR APPLICATION NUMBER: 60/023,851
PRIOR FILING DATE: August 9, 1996
PRIOR APPLICATION NUMBER: 60/035,166
PRIOR FILING DATE: January 10, 1997
PRIOR APPLICATION NUMBER: 60/046,769
PRIOR FILING DATE: May 16, 1997
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 3
LENGTH: 593
TYPE: PRT
Query Match 99.2%; Score 2965; Length 593;
Best Local Similarity 99.5%;
Matches 590; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 1 MDTTIDGFADSYEISSTSFVATDNTDSSIVYLAAEQVLTGPDVSALQLLSNSFESVFDSP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDTTIDGFADSYEISSTSFVATDNTDSSIVYLAAEQVLTGPDVSALQLLSNSFESVFDSP 60
Qy 61 DDFYSDAKLVLSDGREVSFHRCVLSARSSFFKSALAAAKKEKDSNNTAAVKLELKEIAKD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DDFYSDAKLVLSDGREVSFHRCVLSARSSFFKSALAAAKKEKDSNNTAAVKLELKEIAKD 120
Qy 121 YEVGFDSVVTVLAYVYSSRVRPPPKGVSECADENCCHVACRPAVDFMLEVLYLAFIFKIP 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 YEVGFDSVVTVLAYVYSSRVRPPPKGVSECADENCCHVACRPAVDFMLEVLYLAFIFKIP 180
Qy 181 ELITLYQRHLLDVVDKVVIEDTLVILKLANICGKACMKLLDRCKEIIVKSNVDMVSLEKS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ELITLYQRHLLDVVDKVVIEDTLVILKLANICGKACMKLLDRCKEIIVKSNVDMVSLEKS 240
Qy 241 LPEELVKEIIDRRKELGLEVPKVKKHVSNVHKALDSDDIELVKLLLKEDHTNLDDACALH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LPEELVKEIIDRRKELGLEVPKVKKHVSNVHKALDSDDIELVKLLLKEDHTNLDDACALH 300
Qy 301 FAVAYCNVKTATDLLKLDLADVNHRNPRGYTVLHVAAMRKEPQLILSLLEKGASASEATL 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 FAVAYCNVKTATDLLKLDLADVNHRNPRGYTVLHVAAMRKEPQLILSLLEKGASASEATL 360
Qy 361 EGRTALMIAKQATMAVECNNIPEQCKHSLKGRLCVEILECXDKREQIPRDVPPSFAVAAD 420
||||||||||||||||||||||||||||||||||||||| |||||||||||||||||||
Db 361 EGRTALMIAKQATMAVECNNIPEQCKHSLKGRLCVEILEQEDKREQIPRDVPPSFAVAAD 420
Qy 421 ELKMTLLDLENRVALAQRLFPTEAQAAMEIAEMKGTCEFIVTSLEPDRLTGTKRTSPGVK 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 ELKMTLLDLENRVALAQRLFPTEAQAAMEIAEMKGTCEFIVTSLEPDRLTGTKRTSPGVK 480
Qy 481 IAPFRILEEHQSRLKALSKTVELGKCFFPRCSAVLDQIMNCEDLTQLACGEDDTAEKRLQ 540
||||||||||||||||||||||||| ||||||||||||||||||||||||||||||||||
Db 481 IAPFRILEEHQSRLKALSKTVELGKRFFPRCSAVLDQIMNCEDLTQLACGEDDTAEKRLQ 540
Qy 541 KKQRYMEIQETLKKAFSEDNLELGNSSLTDSTSSTSKSTGGKRSNRKLSHRRR 593
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 KKQRYMEIQETLKKAFSEDNLELGNSSLTDSTSSTSKSTGGKRSNRKLSHRRR 593
In regard to claims 8-9, Dong teaches on increasing resistance against Phytophthora infestans and Pseudomonas syrinigae pv maculicola ES4326, (see figures 7-8 and paragraphs [0151] and [0225]), both of which represent biotic stress. Regarding, the claim of increased growth: since both the prior art and the Applicant utilize the identical solution of genetically modifying a plant with NPR1(SAL) protein to increase pathogen resistance, the resulting transgenic plants would inherently exhibit increased growth under those conditions. Because this growth response is a natural physiological result of the same genetic modification disclosed in the prior art, additional reduction to practice is not required.
Accordingly, the claims are anticipated.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 7, is rejected under 35 U.S.C. 103 as being unpatentable over Dong et al. ( US 2002/0138872 A1 (A)), as applied to claims 1-5, 8-9, and 19-20 above, and further in view of Dong et al.(WO 2021262685 A2 (N)).
In regard to claim 7, and the teachings of Dong (A) as applied to claims 1-5, 8-9, and 19-20.
In regard to claim 7, Dong (A) does not teach on using CRISPR.
In regard to claim 7, Dong (N) teaches “[m]ethods of producing a plant that expresses a npr1 protein as described herein or genetically modifying a plant to express a npr1 protein as described herein using a CRISPR/Cas system”, (see page 1354 last paragraph 1st sentence).
Given that Dong (A) teaches on genetically modifying a plant with NPR1 protein, along with Dong’s (N) teaching on using CRISPR to genetically modify a plant with NPR1, it would have been obvious to try to combine teachings knowing that one skilled the art can readily use CRISPR to modify endogenous NPR1 gene. Additionally, both prior art teachings teach on genetically modifying a plant with NPR1.
Therefore, prior to the effective filing date it would have been prima facie obvious to one of ordinary skill in the art to modify the teachings of Dong (A) in view of Dong (N) because one skilled in the art would readily substitute one method of genetically modifying with another.
One would have a reasonable expectation of success in this approach because Dong (A) teaches on genetically modifying a plant with NPR1 to improve biotic or abiotic stress tolerance, while Dong (N) teaches a predictable method for modifying NPR1 using CRISPR editing systems. Consequently, based on the teachings of Dong (A) in view of Dong (N), one would reasonably expect producing a plant with NPR1 with said phenotype.
Subject matter free of prior art
Instant claim 6, appears to be free of the prior art, because even though the concept of expressing npr1 is known the art these particular substitutions or single point mutations have not been taught in the prior art.
Conclusion
No claims are allowed.
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/CHRISTIAN JOSE ORDAZ/Examiner, Art Unit 1663
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662