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 .
Status of Claims
Claims 1, 3, 5-13, 15-19 & 39 are under examination on the merits.
The objection to the specification is withdrawn in light of Applicant’s amendments.
The objection to claims 11 & 17 is withdrawn in light of Applicant’s amendments.
The rejection of claims 1, 4-7 & 9-11 under 35 U.S.C. 101 is withdrawn in light of Applicant’s amendments.
The rejection of claims 1-19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of Applicant’s amendments.
The rejections of claims 6-8, 18 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, are withdrawn in light of Applicant’s amendments.
The rejection of claims 3 & 8 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is withdrawn in light of Applicant’s amendments.
The rejection of claims 1 & 6 under 35 U.S.C. 102(a)(1) as being anticipated by Jiang et al (2018) Phytopathology. 108(8): 980-987 is withdrawn in light of Applicant’s amendments.
The rejection of claims 1 & 7 under 35 U.S.C. 102(a)(1) as being anticipated by Li et al (2019) Frontiers in Plant Science. 10:417 is withdrawn in light of Applicant’s amendments.
The rejection of claims 1, 2, 6, 12, 13 & 19 under 35 U.S.C. 103 as being unpatentable over Jiang et al (2018) Phytopathology. 108(8): 980-987 in view of Barrantes et al (2014) Mol Breeding. 34:1817-1831 is withdrawn in light of Applicant’s amendments.
Objections
Claims 3 & 15 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 12 is objected to because of the following informalities:
Claim 12 (line 3): “a modified susceptibility gene (S-gene) encoding an RPS2-like resistance protein” should read --a modified susceptibility gene (S-gene)-- in light of lines 4-5, which read “wherein the S-gene encodes an RPS2-like resistance protein...”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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, 5-13, 16-19 & 39 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.
Due to Applicant' s amendment of the claims, the rejection is modified from the rejection as set forth in the Office action mailed 8/4/2025, as applied to claims 1, 2, 4-7, 9, 10-14, 16, 17 & 19. Applicant' s arguments filed 11/4/2025 have been fully considered but they are not persuasive.
A. Claims 1, 5-13, 16-19 & 39 require a plant comprising an S-gene that encodes an RPS2-like resistance protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 174.
Claims 1, 5-11 & 13 further require increasing expression or activity of the gene, and claims 1 & 5-11 require targeted DNA modification or introgressing a gene allele to increase or decrease the activity or expression of the gene. Claim 18 requires a plant comprising nucleotide modifications at a genomic locus flanked by Spov3_chr4_93275081 and Spov3_chr4_121142541, while claim 8 requires modification or an introgressed allele flanked by Spov3_chr4_93275081 and Spov3_chr4_121142541.
Claims 12-13, 16-19 & 39 broadly require any plant with reduced susceptibility to a pathogen and any nucleotide modification at a genomic locus encoding S-gene that encodes an RPS2-like resistance protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 174. An RPS2-like resistance protein with 90% identity to the 826 amino acid-long SEQ ID NO: 174 encompasses proteins with 82 amino acid substitutions relative to SEQ ID NO: 174. Claims 1 & 5-11 do not require modifying the RPS2-like gene directly or introducing it into a plant but encompass modifications or interventions to other loci that affect the activity and/or expression of RPS2.
Claims 8 & 18 require that the modification or introgressed allele is flanked by Spov3_chr4_93275081 and Spov3_chr4_121142541, a distance of 27,867,460 nucleotides which potentially encompasses multiple undescribed genes or regulatory elements.
The instant specification describes many RPSs-like resistance protein homologs: SEQ ID NO: 219-240 and 333 (page 39, like 35-page 40, line 2; tables 4 & 6). The specification also describes a SEQ ID NO: 171 with 99.8% sequence identity to SEQ ID NO: 174 and SEQ ID NO: 342 with 91.3% sequence identity to SEQ ID NO: 174. See alignments below. The next most similar sequence, SEQ ID NO: 333, has only 64.5% sequence identity to SEQ ID NO: 174. See third alignment below. Thus, the examples of RPS-like resistance proteins described in the instant specification are not representative of the full scope of the RPS2-like resistance proteins claimed. The specification envisions methods of modifying the S-gene locus and/or increasing activity or expression of the gene (page 7, lines 1-17; page 70 lines 17-30; page 73, lines 4-17). The specification describes mutations in an S-gene in spinach that resulted in resistance to Peronospora effusa (page 80, line -page 81 line), and thus describes removal of 2 C-terminal LRR motifs as associated with increased resistance. This is the only structural feature of the RPS2-like protein provided by the specification contributing to reduced susceptibility. The specification does not describe genes or regulatory elements, and modifications thereto, that affect the activity or expression of RPS2-like genes.
US-18-294-306A-171
Sequence 171, US/18294306A
GENERAL INFORMATION
APPLICANT: KWS Vegetables B.V. (en)
TITLE OF INVENTION: DURABLE DOWNY MILDEW RESISTANCE IN SPINACH (en)
FILE REFERENCE: P14647US00
CURRENT APPLICATION NUMBER: US/18/294,306A
CURRENT FILING DATE: 2024-02-01
NUMBER OF SEQ ID NOS: 342
SEQ ID NO 171
LENGTH: 826
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..826
QUALIFIERS: mol_type = protein
organism = Spinacia oleracea
Query Match 99.8%; Score 4295; Length 826;
Best Local Similarity 99.9%;
Matches 825; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 MAHQIQIPIKMISIIANLFGIGRYHRGVPCDGGTLDNHQSELSSVLIQPQNKRRKVEEFL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAHQIQIPIKMISIIANLFGIGRYHRGVPCDGGTLDNHQSELSSVLIQPQNKRRKVEEFL 60
Qy 61 WFNTEYVDRIIGWLKDSEIDTIGVYGMGGVGKTTLATQLQTRLLNHVVAWVSVGVDFTVY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 WFNTEYVDRIIGWLKDSEIDTIGVYGMGGVGKTTLATQLQTRLLNHVVAWVSVGVDFTVY 120
Qy 121 KLQQDIAGSFGLDLQGDRDAIRRAAMISEFLCRNHNCVLFLDDLWGDFRREDVGIPRKCK 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 KLQQDIAGSFGLDLQGDRDAIRRAAMISEFLCRNHNCVLFLDDLWGDFRREDVGIPRKCK 180
Qy 181 LIVISRLLDVCRKLRCKKVVKVEPLQEEESWQLFNRSIGYGVLNSVDVCRIRKLVYDKCV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LIVISRLLDVCRKLRCKKVVKVEPLQEEESWQLFNRSIGYGVLNSVDVCRIRKLVYDKCV 240
Qy 241 GLPLAITSLATSLRKMVDDDNPSSWREVLENFDLLSAKQPHLEDTFSQLRLSYERLNNKL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GLPLAITSLATSLRKMVDDDNPSSWREVLENFDLLSAKQPHLEDTFSQLRLSYERLNNKL 300
Qy 301 QRCFLYSALFPKGYAIRKEELIRVWIGMELIDDVPSLQARYNMGHSILNKLVDSCLLETY 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QRCFLYSALFPKGYAIRKEELIRVWIGMELIDDVPSLQARYNMGHSILNKLVDSCLLETY 360
Qy 361 DNDNIIKINDLVRHMALSIAGDSYMVEAGIPTNFEFRENLRVVSLVNSSIPSIPSGASLI 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 DNDNIIKINDLVRHMALSIAGDSYMVEAGIPTNFEFRENLRVVSLVNSSIPSIPSGASLI 420
Qy 421 KCHCLSTLLLQHNSLEFIPESFFLHMRGLRVLNLSDTNLIRLPSSIDALEELRVLDLSFC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 KCHCLSTLLLQHNSLEFIPESFFLHMRGLRVLNLSDTNLIRLPSSIDALEELRVLDLSFC 480
Qy 481 QNLKQVTSLSKLLKLQFLNLSQTGIGPAPRSLENLKSLTELNLSSIPEPQKIPSGVLPAL 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 QNLKQVTSLSKLLKLQFLNLSQTGIGPAPRSLENLKSLTELNLSSIPEPQKIPSGVLPAL 540
Qy 541 FRLKRLACYVVEAAIHELQNVNSLEVLDARFLNLCDLSSYVRSQHWCILESYHLQVGFEV 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 FRLKRLACYVVEAAIHELQNVNSLEVLDARFLNLCDLSSYVRSQHWCILESYHLQVGFEV 600
Qy 601 RSEQPYNRRVSLSGCSLTGQEGDYVVLPSNIQELYVDNCRDFRCLSDVLLPVAYRHRNCQ 660
||||||||||||| ||||||||||||||||||||||||||||||||||||||||||||||
Db 601 RSEQPYNRRVSLSRCSLTGQEGDYVVLPSNIQELYVDNCRDFRCLSDVLLPVAYRHRNCQ 660
Qy 661 NGASVDSCNGEQAEVFAGLEMCIISRCQDVKTLFAPSWVEENLQSLELLQVENCRQVKEI 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 NGASVDSCNGEQAEVFAGLEMCIISRCQDVKTLFAPSWVEENLQSLELLQVENCRQVKEI 720
Qy 721 IAEEVVECGHSEGKDAVISLPQLTRLVLTLLPQVHSVYKGLLVCSSLLWCTFMDCPKLKR 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 IAEEVVECGHSEGKDAVISLPQLTRLVLTLLPQVHSVYKGLLVCSSLLWCTFMDCPKLKR 780
Qy 781 LPFSNMDRLEWIEGQEKWWDLLEWDEPESKASLRPLFRCKSVDGDR 826
||||||||||||||||||||||||||||||||||||||||||||||
Db 781 LPFSNMDRLEWIEGQEKWWDLLEWDEPESKASLRPLFRCKSVDGDR 826
US-18-294-306A-342
Sequence 342, US/18294306A
GENERAL INFORMATION
APPLICANT: KWS Vegetables B.V. (en)
TITLE OF INVENTION: DURABLE DOWNY MILDEW RESISTANCE IN SPINACH (en)
FILE REFERENCE: P14647US00
CURRENT APPLICATION NUMBER: US/18/294,306A
CURRENT FILING DATE: 2024-02-01
NUMBER OF SEQ ID NOS: 342
SEQ ID NO 342
LENGTH: 763
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..763
QUALIFIERS: mol_type = protein
organism = Spinacia oleracea
Query Match 91.3%; Score 3929.5; Length 763;
Best Local Similarity 92.1%;
Matches 761; Conservative 0; Mismatches 2; Indels 63; Gaps 2;
Qy 1 MAHQIQIPIKMISIIANLFGIGRYHRGVPCDGGTLDNHQSELSSVLIQPQNKRRKVEEFL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAHQIQIPIKMISIIANLFGIGRYHRGVPCDGGTLDNHQSELSSVLIQPQNKRRKVEEFL 60
Qy 61 WFNTEYVDRIIGWLKDSEIDTIGVYGMGGVGKTTLATQLQTRLLNHVVAWVSVGVDFTVY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 WFNTEYVDRIIGWLKDSEIDTIGVYGMGGVGKTTLATQLQTRLLNHVVAWVSVGVDFTVY 120
Qy 121 KLQQDIAGSFGLDLQGDRDAIRRAAMISEFLCRNHNCVLFLDDLWGDFRREDVGIPRKCK 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 KLQQDIAGSFGLDLQGDRDAIRRAAMISEFLCRNHNCVLFLDDLWGDFRREDVGIPRKCK 180
Qy 181 LIVISRLLDVCRKLRCKKVVKVEPLQEEESWQLFNRSIGYGVLNSVDVCRIRKLVYDKCV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LIVISRLLDVCRKLRCKKVVKVEPLQEEESWQLFNRSIGYGVLNSVDVCRIRKLVYDKCV 240
Qy 241 GLPLAITSLATSLRKMVDDDNPSSWREVLENFDLLSAKQPHLEDTFSQLRLSYERLNNKL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GLPLAITSLATSLRKMVDDDNPSSWREVLENFDLLSAKQPHLEDTFSQLRLSYERLNNKL 300
Qy 301 QRCFLYSALFPKGYAIRKEELIRVWIGMELIDDVPSLQARYNMGHSILNKLVDSCLLETY 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QRCFLYSALFPKGYAIRKEELIRVWIGMELIDDVPSLQARYNMGHSILNKLVDSCLLETY 360
Qy 361 DNDNIIKINDLVRHMALSIAGDSYMVEAGIPTNFEFRENLRVVSLVNSSIPSIPSGASLI 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 DNDNIIKINDLVRHMALSIAGDSYMVEAGIPTNFEFRENLRVVSLVNSSIPSIPSGASLI 420
Qy 421 KCHCLSTLLLQHNSLEFIPESFFLHMRGLRVLNLSDTNLIRLPSSIDALEELRVLDLSFC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 KCHCLSTLLLQHNSLEFIPESFFLHMRGLRVLNLSDTNLIRLPSSIDALEELRVLDLSFC 480
Qy 481 QNLKQVTSLSKLLKLQFLNLSQTGIGPAPRSLENLKSLTELNLSSIPEPQKIPSGVLPAL 540
|||||||||| |
Db 481 QNLKQVTSLSNL------------------------------------------------ 492
Qy 541 FRLKRLACYVVEAAIHELQNVNSLEVLDARFLNLCDLSSYVRSQHWCILESYHLQVGFEV 600
| ||||||||||||||||||||||||||||||||||||||||||||
Db 493 -------C--------ELQNVNSLEVLDARFLNLCDLSSYVRSQHWCILESYHLQVGFEV 537
Qy 601 RSEQPYNRRVSLSGCSLTGQEGDYVVLPSNIQELYVDNCRDFRCLSDVLLPVAYRHRNCQ 660
||||||||||||| ||||||||||||||||||||||||||||||||||||||||||||||
Db 538 RSEQPYNRRVSLSRCSLTGQEGDYVVLPSNIQELYVDNCRDFRCLSDVLLPVAYRHRNCQ 597
Qy 661 NGASVDSCNGEQAEVFAGLEMCIISRCQDVKTLFAPSWVEENLQSLELLQVENCRQVKEI 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 598 NGASVDSCNGEQAEVFAGLEMCIISRCQDVKTLFAPSWVEENLQSLELLQVENCRQVKEI 657
Qy 721 IAEEVVECGHSEGKDAVISLPQLTRLVLTLLPQVHSVYKGLLVCSSLLWCTFMDCPKLKR 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 658 IAEEVVECGHSEGKDAVISLPQLTRLVLTLLPQVHSVYKGLLVCSSLLWCTFMDCPKLKR 717
Qy 781 LPFSNMDRLEWIEGQEKWWDLLEWDEPESKASLRPLFRCKSVDGDR 826
||||||||||||||||||||||||||||||||||||||||||||||
Db 718 LPFSNMDRLEWIEGQEKWWDLLEWDEPESKASLRPLFRCKSVDGDR 763
US-18-294-306A-333
Sequence 333, US/18294306A
GENERAL INFORMATION
APPLICANT: KWS Vegetables B.V. (en)
TITLE OF INVENTION: DURABLE DOWNY MILDEW RESISTANCE IN SPINACH (en)
FILE REFERENCE: P14647US00
CURRENT APPLICATION NUMBER: US/18/294,306A
CURRENT FILING DATE: 2024-02-01
NUMBER OF SEQ ID NOS: 342
SEQ ID NO 333
LENGTH: 826
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..826
QUALIFIERS: mol_type = protein
organism = Beta vulgaris
Query Match 64.5%; Score 2775.5; Length 826;
Best Local Similarity 67.4%;
Matches 566; Conservative 96; Mismatches 135; Indels 43; Gaps 13;
Qy 11 MISIIANLFGIGRYHRGVPCDGGTLD-------NHQSELSSVLIQPQNKRRK-VEEFLWF 62
| :| | | : | : |||| :| |:|||| : || :||||: |: | |
Db 1 MNAIFTKFFRIELFWRDLRCDGGRIDTRVETVVNNQSELGTGHIQQENKRRRLVQPSLCF 60
Qy 63 NTEYVDRIIGWLKDSEIDTIGVYGMGGVGKTTLATQLQTRLLN--------HVVAWVSVG 114
|:| ||||| || : |:|||||||| |||||||||||:||||| | || ||||
Db 61 NSECVDRIISWLDNDEVDTIGVYGMCGVGKTTLATQLETRLLNHDIRFSASHDVAGVSVG 120
Qy 115 VDFTVYKLQQDIAGSFGLDLQGDRDAIRRAAMISEFLCRNHNCVLFLDDLWGDFRREDVG 174
|: :||||||||||:||:||||| | ||||:|| || | ||| ||||||||||:|||
Db 121 VNCSVYKLQQDIAGAFGIDLQGDEDKIRRASMIEAFLSRRDKCVLILDDLWGDFRRKDVG 180
Qy 175 IPRKCKLIVISRLLDVCRKLRCKKVVKVEPLQEEESWQLFNRSIGYGVLNSVDVCRIRKL 234
||::|||::||: ||||| | |:||:||||| | ::|:||| ||| ||||: ||||||||
Db 181 IPKECKLVLISQSLDVCRVLGCEKVLKVEPLSEGKTWKLFNHSIGGGVLNNEDVCRIRKL 240
Qy 235 VYDKCVGLPLAITSLATSLRKMVDDDNPSSWREVLENFDLLSAKQPHLEDTFSQLRLSYE 294
||||| |||||| || ||||| ||| ||||||| : |:: ||||||| |:||||
Db 241 VYDKCAGLPLAIVELAKRLRKMV-DDNGFSWREVLEGTNPFSSRSMHLEDTFSHLKLSYE 299
Qy 295 RLNN-KLQRCFLYSALFPKGYAIRKEELIRVWIGMELIDDVPSLQARYNMGHSILNKLVD 353
||:: |||:||||||::|||:|| :||||||||| :||||: || |:|: ||||||||::
Db 300 RLSDIKLQQCFLYSAIYPKGHAISREELIRVWIGEKLIDDISSLLAQYDKGHSILNKLIN 359
Qy 354 SCLLET-YDNDNIIKINDLVRHMALSIAGDSYMVEAGIPTNFEFRENLRVVSLVNSSIPS 412
||||| | |||:::||||||||||||:|:|||:|: ||||||:|||||:|| |
Db 360 SCLLEACEDYKGCIKIHEVVRHMALSIAGDSFMIEAGVPSKFEFRENVRVVSLINSLISP 419
Qy 413 IPSGASLIKCHCLSTLLLQHNSLEFIPESFFLHMRGLRVLNLSDTNLIRLPSSIDALEEL 472
|||||| | | ||||||||| || |||| || || ||||||||| |||||||| |||||
Db 420 IPSGAS-SKYHTLSTLLLQHNPLELIPESLFLQMRALRVLNLSDTRLIRLPSSIGALEEL 478
Qy 473 RVLDLSFCQNLKQVTSLSKLLKLQFLNLSQTGIGPAPRSLENLKSLTELNLSSIPEPQKI 532
|||||||||||||| :||||||||||||||| | | ||| || |||||||||||| ||
Db 479 RVLDLSFCQNLKQVAALSKLLKLQFLNLSQTTIEKVPCSLEKLKRLTELNLSSIPEPTKI 538
Qy 533 PSGVLPALFRLKRLACYVVEAAIHELQNVNSLEVLDARFLNLCDLSSYVRSQHWCILESY 592
|| || || |||:| |:|: ||||| :||||:||||| :|||||:|||||||||||||
Db 539 PSVVLLALCRLKKLTCHVI-GTIHELQRMNSLEILDARFFSLCDLSAYVRSQHWCILESY 597
Qy 593 HLQVGFEVRSEQPYNRRVSLSGCSLTGQEGDYVVLPSNIQELYVDNCRDFRCLSDVLLPV 652
||:| ||::|||| ||||| | |||||| |:||||||||||||||| || ||||: ||
Db 598 SLQLGCEVQAEQPYIRRVSLQGFSLTGQE-QYIVLPSNIQELYVDNCRGFRRLSDVMYPV 656
Qy 653 AYRHRNCQNGASVDSCNGEQAEVFAGLEMCIISRCQDVKTLFAPSWVEENLQSLELLQVE 712
||:|::||| ||| ||:|:|||| ||:|||| :|| ||||||||||||
Db 657 AYQHKSCQN-----------YEVFLSLEICVISRCPDVETLFAANWV-ENLQSLELLQVE 704
Qy 713 NCRQVKEIIAEEVVECG-HSEGKDAVISLPQLTRLVLTLLPQVHSVYKGLLVCSSLLWCT 771
:| |:||:| || || | : || | |:| |: :|: | |||: |:||| |||:||| ||
Db 705 DCGQLKEVITEEFVERGVYPEGISAPINLLQIRQLIFTRLPQMESIYKGQLVCASLLSCT 764
Qy 772 FMDCPKLKRLPFSNMD--------RLEWIEGQEKWWDLLEWDEPESKASLRPLFRCKSVD 823
|:||||| ||||| | |||||||::|||::||||:| |:| :|||||||:|
Db 765 FLDCPKLTRLPFSCMGNGEETFPWRLEWIEGEKKWWEMLEWDQPGSEALFKPLFRCKSLD 824
This instant specification describes 9 markers within the chromosomal region flanked by Spov3_chr4_93275081 and Spov3_chr4_121142541 (Table 1). The instant specification describes that a chromosome region can contain one or more ORFs associated with disease resistance, and describes that three genes were identified in the region of the instant claims (page 36, lines 5-17). The instant specification does not describe non-coding elements present within the recited region that influence the expression or activity of the RPS2-like resistance protein gene.
RPS2-like resistance proteins are known in the prior art. RPS2 in Arabidopsis, for which the genus of proteins is named, induces a defense response in a gene-for-gene interaction (Mauricio et al (2003) Genetics 163: 735–746. Published 2/1/2003, hereafter Mauricio. page 735, left column, paragraph 1). RPS2-like proteins contain a nucleotide-binding site and leucine-rich repeat region (LRR); the LRR determines resistance specificity by recognizing avirulence products of pathogens or their downstream products (Mauricio, page 735, left column paragraph 2-right column paragraph 1). Given their role in pathogen recognition, it is understood in the art that different RPS2-like proteins within a plant do not necessarily respond to a given pathogen in the same way if at all. For example, in tea plants exposed to Exobasidium vexans, genes annotated as RPS2-like were upregulated at all time points while others were not upregulated at different infection stages (Jayaswall et al (2016) Scientific Reports. 6:30412. published 7/28/2016: figure 5A, page 11 page 3). Even within species, different alleles of RPS2-like genes may provide different levels of resistance or susceptibility. Multiple RPS2 alleles are known from different Arabidopsis ecotypes (Mauricio tables 1, 2) and variation of amino acid residues in the N-terminal end of RPS2 may be consistent with diversifying selection on the gene (Mauricio page 744, right column, paragraph 1).
RPS2-like resistance proteins with an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 174 are not described in the prior art over the scope of the claims. A gene encoding a hypothetical resistance protein in spinach was known prior to filing of the instant application with >99% sequence identity to SEQ ID NO: 174 (NCBI reference sequence XP_021845706.1, available 8/1/2017; see alignment below). In other species, the closest protein sequence of NCBI Reference Sequence XP_010696096.1 (available 11/28/2016) shared 67% sequence identity with SEQ ID NO: 174 (see second alignment below). The Beta vulgaris gene is annotated to be an RPS2-like resistance protein.
Spinacia oleracea
Score
Expect
Method
Identities
Positives
Gaps
1681 bits(4353)
0.0
Compositional matrix adjust.
823/826(99%)
825/826(99%)
0/826(0%)
Query 1 MAHQIQIPIKMISIIANLFGIGRYHRGVPCDGGTLDNHQSELSSVLIQPQNKRRKVEEFL 60
MAHQIQIPIKMISIIANLFGIGRYHRGVPCDGGTLDNHQSELSSVLIQPQNKRRKVEEFL
Sbjct 1 MAHQIQIPIKMISIIANLFGIGRYHRGVPCDGGTLDNHQSELSSVLIQPQNKRRKVEEFL 60
Query 61 WFNTEYVDRIIGWLKDSEIDTIGVYGMGGVGKTTLATQLQTRLLNHVVAWVSVGVDFTVY 120
WFNTEYVDRIIGWLKDSEIDTIGVYGMGGVGKTTLATQLQTRLLNHVVAWVSVGVDFTVY
Sbjct 61 WFNTEYVDRIIGWLKDSEIDTIGVYGMGGVGKTTLATQLQTRLLNHVVAWVSVGVDFTVY 120
Query 121 KLQQDIAGSFGLDLQGDRDAIRRAAMISEFLCRNHNCVLFLDDLWGDFRREDVGIPRKCK 180
KLQQDIAGSFGLDLQGDRDAIRRAAMISEFLCRNHNCVLFLDDLWGDFRREDVGIPRKCK
Sbjct 121 KLQQDIAGSFGLDLQGDRDAIRRAAMISEFLCRNHNCVLFLDDLWGDFRREDVGIPRKCK 180
Query 181 LIVISRLLDVCRKLRCKKVVKVEPLQEEESWQLFNRSIGYGVLNSVDVCRIRKLVYDKCV 240
LIVISRLLDVCRKLRCKKVVKVEPLQEEESWQLFNRSIGYGVLNSVDVCRIRKLVYDKCV
Sbjct 181 LIVISRLLDVCRKLRCKKVVKVEPLQEEESWQLFNRSIGYGVLNSVDVCRIRKLVYDKCV 240
Query 241 GLPLAITSLATSLRKMVDDDNPSSWREVLENFDLLSAKQPHLEDTFSQLRLSYERLNNKL 300
GLPLAITSLATSLRKMVDDDNPSSWREVLENFDLLSAKQPHLEDTFSQLRLSYERLNNK
Sbjct 241 GLPLAITSLATSLRKMVDDDNPSSWREVLENFDLLSAKQPHLEDTFSQLRLSYERLNNKP 300
Query 301 QRCFLYSALFPKGYAIRKEELIRVWIGMELIDDVPSLQARYNMGHSILNKLVDSCLLETY 360
QRCFLYSAL+PKGYAIRKEELIRVWIGMELIDDVPSLQARYNMGHSIL+KLVDSCLLETY
Sbjct 301 QRCFLYSALYPKGYAIRKEELIRVWIGMELIDDVPSLQARYNMGHSILSKLVDSCLLETY 360
Query 361 DNDNIIKINDLVRHMALSIAGDSYMVEAGIPTNFEFRENLRVVSLVNSSIPSIPSGASLI 420
DNDNIIKINDLVRHMALSIAGDSYMVEAGIPTNFEFRENLRVVSLVNSSIPSIPSGASLI
Sbjct 361 DNDNIIKINDLVRHMALSIAGDSYMVEAGIPTNFEFRENLRVVSLVNSSIPSIPSGASLI 420
Query 421 KCHCLSTLLLQHNSLEFIPESFFLHMRGLRVLNLSDTNLIRLPSSIDALEELRVLDLSFC 480
KCHCLSTLLLQHNSLEFIPESFFLHMRGLRVLNLSDTNLIRLPSSIDALEELRVLDLSFC
Sbjct 421 KCHCLSTLLLQHNSLEFIPESFFLHMRGLRVLNLSDTNLIRLPSSIDALEELRVLDLSFC 480
Query 481 QNLKQVTSLSKLLKLQFLNLSQTGIGPAPRSLENLKSLTELNLSSIPEPQKIPSGVLPAL 540
QNLKQVTSLSKLLKLQFLNLSQTGIGPAPRSLENLKSLTELNLSSIPEPQKIPSGVLPAL
Sbjct 481 QNLKQVTSLSKLLKLQFLNLSQTGIGPAPRSLENLKSLTELNLSSIPEPQKIPSGVLPAL 540
Query 541 FRLKRLACYVVEAAIHELQNVNSLEVLDARFLNLCDLSSYVRSQHWCILESYHLQVGFEV 600
FRLKRLACYVVEAAIHELQNVNSLEVLDARFLNLCDLSSYVRSQHWCILESYHLQVGFEV
Sbjct 541 FRLKRLACYVVEAAIHELQNVNSLEVLDARFLNLCDLSSYVRSQHWCILESYHLQVGFEV 600
Query 601 RSEQPYNRRVSLSGCSLTGQEGDYVVLPSNIQELYVDNCRDFRCLSDVLLPVAYRHRNCQ 660
RSEQPYNRRVSLSGCSLTGQEGDYVVLPSNIQELYVDNCRDFRCLSDVLLPVAYRHRNCQ
Sbjct 601 RSEQPYNRRVSLSGCSLTGQEGDYVVLPSNIQELYVDNCRDFRCLSDVLLPVAYRHRNCQ 660
Query 661 NGASVDSCNGEQAEVFAGLEMCIISRCQDVKTLFAPSWVEENLQSLELLQVENCRQVKEI 720
NGASVDSCNGEQAEVFAGLEMCIISRCQDVKTLFAPSWVEENLQSLELLQVENCRQVKEI
Sbjct 661 NGASVDSCNGEQAEVFAGLEMCIISRCQDVKTLFAPSWVEENLQSLELLQVENCRQVKEI 720
Query 721 IAEEVVECGHSEGKDAVISLPQLTRLVLTLLPQVHSVYKGLLVCSSLLWCTFMDCPKLKR 780
IAEEVVECGHSEGKDAVISLPQLTRLVLTLLPQVHSVYKGLLVCSSLLWCTFMDCPKLKR
Sbjct 721 IAEEVVECGHSEGKDAVISLPQLTRLVLTLLPQVHSVYKGLLVCSSLLWCTFMDCPKLKR 780
Query 781 LPFSNMDRLEWIEGQEKWWDLLEWDEPESKASLRPLFRCKSVDGDR 826
LPFSNMDRLEWIEGQEKWWDLLEWDEPESKASLRPLFRCKSVDGDR
Sbjct 781 LPFSNMDRLEWIEGQEKWWDLLEWDEPESKASLRPLFRCKSVDGDR 826
Beta vulgaris
Score
Expect
Method
Identities
Positives
Gaps
1071 bits(2771)
0.0
Compositional matrix adjust.
564/840(67%)
661/840(78%)
43/840(5%)
Query 11 MISIIANLFGIGRYHRGVPCDGGTLD-------NHQSELSSVLIQPQNKRRK-VEEFLWF 62
M +I F I + R + CDGG +D N+QSEL + IQ +NKRR+ V+ L F
Sbjct 2 MNAIFTKFFRIELFWRDLRCDGGRIDTRVETVVNNQSELGTGHIQQENKRRRLVQPSLCF 61
Query 63 NTEYVDRIIGWLKDSEIDTIGVYGMGGVGKTTLATQLQTRLLNHV--------VAWVSVG 114
N+E VDRII WL + E+DTIGVYGM GVGKTTLATQL+TRLLNH VA VSVG
Sbjct 62 NSECVDRIISWLDNDEVDTIGVYGMCGVGKTTLATQLETRLLNHDIRFSASHDVAGVSVG 121
Query 115 VDFTVYKLQQDIAGSFGLDLQGDRDAIRRAAMISEFLCRNHNCVLFLDDLWGDFRREDVG 174
V+ +VYKLQQDIAG+FG+DLQGD D RRA+MI F R CVL LDDLWGDFRR+DVG
Sbjct 122 VNCSVYKLQQDIAGAFGIDLQGDEDKTRRASMIEAFFSRRDKCVLILDDLWGDFRRKDVG 181
Query 175 IPRKCKLIVISRLLDVCRKLRCKKVVKVEPLQEEESWQLFNRSIGYGVLNSVDVCRIRKL 234
IP++CKL++IS+ LDVCR L C+KV+KVEPL E ++W+LFN SIG GVLN+ DVCRIRKL
Sbjct 182 IPKECKLVLISQSLDVCRVLGCEKVLKVEPLSEGKTWKLFNHSIGGGVLNNEDVCRIRKL 241
Query 235 VYDKCVGLPLAITSLATSLRKMVDDDNPSSWREVLENFDLLSAKQPHLEDTFSQLRLSYE 294
VYDKC GLPLAI LA LRKMV DDN SWREVLE + S++ HLEDTFS L+LSYE
Sbjct 242 VYDKCAGLPLAIVELAKRLRKMV-DDNGFSWREVLEGTNPFSSRSMHLEDTFSHLKLSYE 300
Query 295 RLNN-KLQRCFLYSALFPKGYAIRKEELIRVWIGMELIDDVPSLQARYNMGHSILNKLVD 353
RL++ KLQ+CFLYSA++PKG+AI +EELIRVWIG +LIDD+ SL A+Y+ GHSILNKL++
Sbjct 301 RLSDIKLQQCFLYSAIYPKGHAISREELIRVWIGEKLIDDISSLLAQYDKGHSILNKLIN 360
Query 354 SCLLET-YDNDNIIKINDLVRHMALSIAGDSYMVEAGIPTNFEFRENLRVVSLVNSSIPS 412
SCLLE D IKI+++VRHMALSIAGDS+M+EAG+P+ FEFREN+RVVSL+NS I
Sbjct 361 SCLLEACEDYKGCIKIHEVVRHMALSIAGDSFMIEAGVPSKFEFRENVRVVSLINSLISP 420
Query 413 IPSGASLIKCHCLSTLLLQHNSLEFIPESFFLHMRGLRVLNLSDTNLIRLPSSIDALEEL 472
IPSGAS K H LSTLLLQHN LE IPES FL MR LRVLNLSDT LIRLPSSI ALEEL
Sbjct 421 IPSGAS-SKYHTLSTLLLQHNPLELIPESLFLQMRALRVLNLSDTRLIRLPSSIGALEEL 479
Query 473 RVLDLSFCQNLKQVTSLSKLLKLQFLNLSQTGIGPAPRSLENLKSLTELNLSSIPEPQKI 532
RVLDLSFCQNLKQV +LSKLLKLQFLNLSQT I P SLE LK LTELNLSSIPEP KI
Sbjct 480 RVLDLSFCQNLKQVAALSKLLKLQFLNLSQTTIEKVPCSLEKLKRLTELNLSSIPEPTKI 539
Query 533 PSGVLPALFRLKRLACYVVEAAIHELQNVNSLEVLDARFLNLCDLSSYVRSQHWCILESY 592
PS VL AL RLK+L C+V+ IHELQ +NSLE+LDARF +LCDLS+YVRSQHWCILESY
Sbjct 540 PSVVLLALCRLKKLTCHVI-GTIHELQRMNSLEILDARFFSLCDLSAYVRSQHWCILESY 598
Query 593 HLQVGFEVRSEQPYNRRVSLSGCSLTGQEGDYVVLPSNIQELYVDNCRDFRCLSDVLLPV 652
LQ+G EV++EQPY RRVSL G SLTGQE Y+VLPSNIQELYVDNCR FR LSDV+ PV
Sbjct 599 SLQLGCEVQAEQPYIRRVSLQGFSLTGQE-QYIVLPSNIQELYVDNCRGFRRLSDVMYPV 657
Query 653 AYRHRNCQNGASVDSCNGEQAEVFAGLEMCIISRCQDVKTLFAPSWVEENLQSLELLQVE 712
AY+H++CQN EVF+ LE+C+ISRC DV+TLFA +WV ENLQSLELLQVE
Sbjct 658 AYQHKSCQN-----------YEVFSSLEICVISRCPDVETLFAANWV-ENLQSLELLQVE 705
Query 713 NCRQVKEIIAEEVVECG-HSEGKDAVISLPQLTRLVLTLLPQVHSVYKGLLVCSSLLWCT 771
+C Q+KE+I EE VE G + EG A I+L Q+ +L+ T LPQ+ S+YKG LVC+SLL CT
Sbjct 706 DCGQLKEVITEEFVERGVYPEGISAPINLLQIRQLIFTRLPQMESIYKGQLVCASLLSCT 765
Query 772 FMDCPKLKRLPFSNMD--------RLEWIEGQEKWWDLLEWDEPESKASLRPLFRCKSVD 823
F+DCPKL RLPFS M RLEWIEG++KWW++LEWD+P S+A +PLFRCKS+D
Sbjct 766 FLDCPKLTRLPFSCMGNGEETFPWRLEWIEGEKKWWEMLEWDQPGSEALFKPLFRCKSLD 825
One of skill in the art would not recognize that Applicant was in possession of the necessary common attributes or features of the genus of RPS2-like genes nor of the genus of other genes, including pathogen virulence genes, that influence the expression and activity of RPS2-like genes nor genetic elements within the region flanked by Spov3_chr4_93275081 and Spov3_chr4_121142541 that influence susceptibility to a pathogen, in view of the disclosed species.
Hence, Applicant has not described S-genes, modified or not, encoding RPS2-like resistance proteins at least 90% identical to SEQ ID NO: 174 providing reduced susceptibility to pathogens in any species of plant, nor factors, genes, or regulatory elements that increase expression or activity of an RPS2-like resistance gene over the full scope of the claims, and the specification fails to provide an adequate written description of the claimed invention. Therefore, given the lack of written description in the specification with regard to the structural and functional characteristics of the claimed compositions, Applicant does not appear to have been in possession of the claimed genus at the time this application was filed.
Applicant urges that the amended claims are directed to an RPS2-like resistance protein comprising an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 174. Applicant urges that because numerous sequences homologous to the RPS2-like resistance protein are described in tables 4 & 6 and two sequences have been provided with over 90% sequence identity to SEQ ID NO: 174, the claims are more narrowly tailored to what is described by the specification (Remarks, page 11, paragraphs 2-3).
This argument is unpersuasive, because 2 example sequences, which incorporate just 3 amino acid mismatches and a deletion (alignments above, or specification page 80, lines 3-20), do not encompass the full scope of the variation in DNA modifications encompassed by the instant claims. An amino acid sequence at least 90% identical to the sequence of SEQ ID NO: 174 encompasses sequences with as many as 82 amino acid substitutions. Applicant has not described sequences over this full scope that would function to reduce susceptibility to a pathogen in a plant. Moreover, claims 1 & 5-11 do not require modifying the RPS2-like gene directly or introducing it into a plant but encompass modifications or introgressions of other loci or alleles that affect the activity and/or expression of RPS2-like protein. Applicant has not described any other loci or regulatory elements that would influence the function or expression of the recited protein. Thus, one of skill in the art would not reasonably conclude that Applicant was in possession of plants comprising reduced susceptibility to a pathogen over the full scope of the claimed invention.
B. Claim 19 recites an F1 progeny plant from the plant of claim 12.
First generation progeny of an inbred line may be considered described, because one set of the inherited genome is known in all first-generation progeny. However, because of crossing over, first generation progeny of lines that are not inbred will not necessarily share any common genetic component. The plant of claim 12 is not required to be inbred or even homozygous for the one or more nucleotide modifications. Therefore, a plant that is an F1 progeny of the plant of claim 12 may not share any given trait with the parental plant or with other progeny, including the trait of a modified S-gene encoding an RPS2-like resistant protein or reduced susceptibility to a pathogen.
The specification fails to describe the structural features such as traits or genes that distinguish a plant that is an F1 progeny of the plant of claim 12 from other plants that are not F1 progeny of said plant.
The specification describes M2 families and seedlings from selfed M1 plants generated by EMS mutation of inbred line B11-509, as well as M3 families obtained by selfing M2 plants (page 77 line 3-13). The specification teaches an EMS22-20 line from an individual mutant M3 plant (page 79, lines 28-29 & page 86 line 32-page 87 line 1; table 7). The specification also describes backcross F2 populations for genetic mapping of the mutation (page 78 lines 1-6). The specification provides prophetic examples of plants of various species that comprise mutant alleles altering expression of the S-gene (examples 9-17) but these examples do not specifically teach progeny descended from the plants comprising the genetic modification.
Given the variety of the genus of “progeny” of the plant of claim 12 and the lack of a required shared feature, one of skill in the art would not recognize that Applicant was in possession of the necessary common attributes or features of the genus.
Applicant urges that claim 19 has been amended to specify F1 progeny and urges that F1 progeny are described by the specification (Remarks, page 12, paragraph 2).
This argument is unpersuasive, because while F1 progeny may be considered described in an inbred line or one homozygous for the trait, the plant of amended claim 12 is not required to be inbred or homozygous for the recited nucleotides modifications. Thus, an F1 progeny would not necessarily share any defining feature with the plant of claim 12 or other F1 progeny. Because there is no structural feature to define an F1 progeny of the plant of claim 12 from an F1 progeny of any other plant, Applicant has not demonstrated possession of F1 progeny over the full scope of the claims.
Page 17 of the Office Action mailed 8/4/2025 outlines the instant specification’s description of families of plants derived from an EMS mutation of an inbred line (page 17, paragraph 4) and states that the prophetic examples do not specifically teach progeny descended from plants comprising the genetic modification (page 18, paragraph 1). Claim 12 is not limited to plants derived from the inbred line(s) described in the specification, and so the specification does not provide sufficient Written Description over the full scope of the claimed genus of F1 progeny of a plant of claim 12.
Scope of Enablement
Claims 1, 5-13, 16-19 & 39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for reduced susceptibility to pathogens in a spinach plant comprising a modified locus encoding a protein with the sequence of SEQ ID NO: 174, does not reasonably provide enablement for any species of plant with reduced susceptibility to any pathogen or encoding a protein with a sequence at least 90% identity to SEQ ID NO: 174 or comprising modifications to other genes that affect the expression or activity of any gene encoding an RPS2-like protein. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Due to Applicant' s amendment of the claims, the rejection is modified from the rejection as set forth in the Office action mailed 8/4/2025, as applied to claims 1, 2, 4-7, 9, 10-14, 16, 17 & 19. Applicant' s arguments filed 11/4/2025 have been fully considered but they are not persuasive.
Claims 1, 5-13, 16-19 & 39 require a plant comprising an S-gene that encodes an RPS2-like resistance protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 174.
Claims 1, 5-11 & 13 further require increasing expression or activity of the gene, and claims 1 & 5-11 require targeted DNA modification or introgressing a gene allele to increase or decrease the activity or expression of the gene. Claim 18 requires a plant comprising nucleotide modifications at a genomic locus flanked by Spov3_chr4_93275081 and Spov3_chr4_121142541, while claim 8 requires modification or an introgressed allele flanked by Spov3_chr4_93275081 and Spov3_chr4_121142541.
Claims 12-13, 16-19 & 39 broadly require any plant with reduced susceptibility to a pathogen and any nucleotide modification at a genomic locus encoding S-gene that encodes an RPS2-like resistance protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 174. An RPS2-like resistance protein with 90% identity to the 826 amino acid-long SEQ ID NO: 174 encompasses proteins with 82 amino acid substitutions relative to SEQ ID NO: 174. Claims 1 & 5-11 do not require modifying the RPS2-like gene directly or introducing it into a plant but broadly encompass modifications or interventions to other loci that affect the activity and/or expression of RPS2.
Claims 8 & 18 require that the modification or introgressed allele is flanked by Spov3_chr4_93275081 and Spov3_chr4_121142541, a distance of 27,867,460 nucleotides which potentially encompasses undescribed genes or regulatory elements.
The instant specification teaches a nucleotide modification resulting in increased expression of a RPS2-like gene in spinach and increased resistance to Peronospora effusa (figure 6, page 77, lines 3-34). The specification also teaches a mapping population for the resistance trait (page 78, lines 1-11). The resistant plants with crossovers or introgressions at the locus read on plants comprising one or more nucleotide modifications at a genomic locus wherein the genomic locus comprises a modified susceptibility gene (as required by claim 12). The specification teaches prophetic examples of plants of various species that comprise mutant alleles altering expression of the S-gene (examples 9-17) and orthologous RPS2-like genes in various species (tables 4 & 6) but these examples do not teach working examples of mutations in the genes resulting plants with increased expression or activity of the gene encoding an RPS2-like resistance protein or reduced susceptibility to a pathogen. The specification also does not teach genes or regulatory elements, and modifications thereto, that affect the activity or expression of RPS2-like genes.
This instant specification teaches 9 markers within the chromosomal region flanked by Spov3_chr4_93275081 and Spov3_chr4_121142541 (Table 1). The instant specification teaches three genes were identified in the region of the instant claims (page 36, lines 5-17). The instant specification does not teach non-coding elements or coding genes other than the RPS2-like resistance gene present within the recited region that influence the expression or activity of the RPS2-like resistance protein gene.
RPS2 in Arabidopsis is known in the art to induce a defense response in a gene-for-gene interaction (Mauricio et al (2003) Genetics 163: 735–746. Published 2/1/2003, hereafter Mauricio. page 735, left column, paragraph 1).
RPS2-like proteins contain a nucleotide-binding site and leucine-rich repeat region (LRR); the LRR determines resistance specificity by recognizing avirulence products of pathogens or their downstream products (Mauricio, page 735, left column paragraph 2-right column paragraph 1). Given their role in pathogen recognition, it is understood in the art that different RPS2-like proteins within a plant do not necessarily respond to a given pathogen in the same way as other RPS2-like proteins if at all. For example, in tea plants exposed to Exobasidium vexans, genes annotated as RPS2-like were upregulated at all time points while others were not upregulated at different infection stages (Jayaswall et al (2016) Scientific Reports. 6:30412. published 7/28/2016: figure 5A, page 11 page 3). In impatiens infected with Plasmopara obducens, not all genes functionally similar to RPS2-like proteins were significantly upregulated in resistant plants, and R genes such as RPS2 exhibit polymorphism regarding their role in defense (Bhattarai et al (2018) International Journal of Molecular Sciences. 19. 2057 (published 7/15/2018) page 12, paragraph 2).
Even within species different alleles of RPS2-like genes may provide different levels of resistance or susceptibility. Multiple RPS2 alleles are known from different Arabidopsis ecotypes (Mauricio tables 1, 2) and variation of amino acid residues in the N-terminal end of RPS2 may be consistent with diversifying selection on the gene (Mauricio page 744, right column, paragraph 1).
Given that RPS2-like proteins and their alleles are highly variable in structure, in expression patterns, and in pathogen recognition specificity especially across species, and given the few working examples provided by the Applicant, one of ordinary skill in the art would be required to generate and test an undue number of RPS2-like proteins to determine which proteins reduce susceptibility to a pathogen when increased in activity or expression. Thus, claims 1, 5-13, 16-19 & 39 are not enabled over the full scope of increasing the activity or expression of any S-gene encoding an RPS2-like resistance protein that is at least 90% identical to SEQ ID NO: 174 or a plant comprising one or more nucleotide modifications at any locus comprising a modified susceptibility gene at least 90% identical to SEQ ID NO: 174 or progeny thereof in any plant.
Applicant urges that claims 1 & 12 have been amended to specify the S-gene encodes an RPS2-like resistance protein comprising an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 174, and so the claims are narrowly tailored to the working examples and do not require testing an undue number of RPS2-like proteins (Remarks, page 12, paragraph 6-page 13, paragraph 1).
This argument is unpersuasive, because RPS2-like proteins are highly variable in structure, in expression patterns, and in pathogen recognition specificity especially across species. The two examples in spinach of sequences of RPS2-like proteins within the genus of RPS2-like resistance proteins comprising an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 174 would still require an undue amount of experimentation for one of ordinary skill in the art to generate and test a large number of RPS2-like proteins in different plant species and in response to different pathogens.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Victoria L DeLeo whose telephone number is (703)756-5998. The examiner can normally be reached M-F 8:00am-4pm EDT.
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/VICTORIA L DELEO/Examiner, Art Unit 1662
/Anne Kubelik/Primary Examiner, Art Unit 1663
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