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
Claims 5-8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 8/8/2025.
Applicant's election with traverse of Group I (current claims 1-4 & 11-22) in the reply filed on 8/8/2025 is acknowledged. The traversal is on the ground(s) that a search for methods of producing and selecting a Raphanus sativus plant comprising a gene that encodes a protein that confers resistance would likely encompass search results for markers used for identifying and selecting the resistant plants. Applicant urges that all groups involve Raphanus sativus plants comprising a gene that encodes a protein that confers resistance to Albugo candida or markers for identifying and selecting the resistant plants. Applicant urges that the search would likely be co-extensive and would not present undue burden (Remarks, page 11, paragraphs 2-4).
This argument is not found persuasive because a marker encompassed by group II which detects a thymine at position 2240 of SEQ ID NO: 2 or at a corresponding position of a homologous sequence need not only be used for the identification of a Raphanus sativus plant having a gene encoding a Albugo candida resistance protein. A marker capable of detecting a thymine at position 2240 of a sequence that has at least 95% sequence identity to SEQ ID NO: 2 need not even be specific to this single position in Raphanus sativus, so determining the presence of the marker in claim 5 would not even necessarily require the gene with at least 95% sequence identity to SEQ ID NO: 2 to be present in a Raphanus sativus plant. The search for all encompassed markers of Group II is much broader than the search for the plants and methods of Group I and is not co-extensive. Group II thus presents an undue search burden.
The requirement is still deemed proper and is therefore made FINAL.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Status of Claims
Claims 1-4 & 11-22 are under examination on the merits.
Claims 5-8 have been withdrawn.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
Claim Objections
Claims 1 & 4 are objected to because of the following informalities:
Claim 1 (line 28), claim 16 (line 23), claim 17 (line 26), claim 18 (line 21) and claim 22 (line 17): the acronym LRR should be written out in full in its first usage in a claim.
Claim 4 (line 3) and claim 13 (line 2): the acronym NCIMB should be written out in full in its first usage in a claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 3 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.
Claim 3 recites the limitation “the nucleotide sequence having the coding sequence having at least 95% sequence identity to SEQ ID NO: 2" in line 2. There is insufficient antecedent basis for this limitation in the claim. A nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 2, as required by claim 1, still encompasses many potential sequences and it is unclear which specific nucleotide sequence is “the” sequence required in claim 3.
Claim 3 requires that the gene comprises a thymine at a corresponding position of a homologous sequence that has at least 95% sequence identity to SEQ ID NO: 2. It is unclear if the gene, which has the coding sequence having at least 95% sequence identity to SEQ ID NO: 2 (lines 1-3), must also have a thymine at any corresponding position of a sequence homologous to this first sequence that also has 95% sequence identity to instant SEQ ID NO: 2 (lines 4-5), which could potentially be any position. Alternatively, it is possible that this limitation was meant to convey that the gene comprises a thymine at a corresponding position to any thymine in SEQ ID NO: 2. Because there are multiple interpretations as to what the corresponding position of a homologous sequence is meant to encompass, claim 3 is indefinite.
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, 3, & 11-22 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.
Claims 1, 3, 11-12 & 14-22 require a gene encoding a protein conferring resistance to Albugo candida comprising a nucleotide sequence having a coding sequence of at least 95% sequence identity to SEQ ID NO: 2 or encoding a protein having an amino acid sequence of at least 95% sequence identity to SEQ ID NO: 3 or comprising a nucleotide sequence encoding at least the amino acids at position 15 to position 195, position 209 to position 432, or position 540 to position 1023 of SEQ ID NO: 3, or a nucleotide sequence encoding an LRR domain having at least 95% sequence identity to the amino acids at position 540 to 1023 of SEQ ID NO: 3. Claim 13 requires that the gene is introgressed from NCIMB 43737 or from a progeny plant thereof that has retained the gene. Because a progeny plant may have undergone crossing over or spontaneous mutation, a plant encompassed by claim 13 will not necessarily comprise a nucleotide sequence with 100% sequence identity to SEQ ID NO: 2 or encoding an amino acid sequence with 100% identity to instant SEQ ID NO: 3.
Nucleotide sequences encoding a protein having an amino acid sequence of at least 95% sequence identity to the 1128 amino acid-long SEQ ID NO: 3 encompass sequences with 56 substitutions relative to SEQ ID NO: 3. Nucleotide sequences having a coding sequence of at least 95% sequence identity to the 3384 nucleotide-long SEQ ID NO: 2 encompass sequences with 169 substitutions relative to SEQ ID NO: 2, including sequences where every substitution is in a position that results in a different amino acid. This would result in an amino acid sequence with 169 substitutions relative to instant SEQ ID NO: 3, or 85% sequence identity to SEQ ID NO: 3.
A nucleotide sequence encoding an LRR domain having at least 95% sequence identity to the amino acids at position 540 to 1023 of SEQ ID NO: 3 encompasses sequences with 24 substitutions relative to the 483 amino acid long segment. Such a sequence would only need to share 459 amino acids with the 1128 amino acid long protein of SEQ ID NO: 3, or 40% sequence identity. Similarly, a sequence encoding the amino acids at position 15 to position 195 of SEQ ID NO: 3 encompasses sequences that share only 180 amino acids with SEQ ID NO: 3, or 16% identity, and a sequence encoding the amino acids at position 209 to position 432 encompasses sequences that share only 223 amino acids with instant SEQ ID NO: 3, or 19.8% identity.
Moreover, “an” amino acid sequence of SEQ ID NO: 3 encompasses any amino acid sequence of at least two consecutive amino acids found in SEQ ID NO: 3 and “a” coding sequence of SEQ ID NO: 2 encompasses any nucleic acid sequence of at least two consecutive nucleotides found in SEQ ID NO: 2. Therefore, claims 1 & 16-22 encompass any gene conferring resistance to Albugo candida comprising a nucleotide sequence of at least 2 consecutive nucleic acids either found in SEQ ID NO: 2 or capable of encoding 2 consecutive amino acids found in SEQ ID NO: 3.
The instant specification has provided a single example of a genomic nucleic acid sequence (SEQ ID NO: 1) with a single coding sequence (SEQ ID NO: 2) encoding one protein with an amino acid sequence (SEQ ID NO: 3). The instant specification has not taught any variants of the provided nucleic and amino acid sequences that do not have 100% sequence identity to SEQ ID NOs: 1 & 2 or 3 respectively or that comprise positions 15 to 195, 209 to 432 or 540 to 1023 of SEQ ID NO: 3 but do not comprise SEQ ID NO: 3 in its entirety.
The specification describes the protein of SEQ ID NO: 3 as a TIR-NBS-LRR protein comprising a Toll/Interleukin-1 receptor (TIR), nucleotide binding site (NBS) domain, and Leucine Rich Repeat (LRR) domain (paragraph [0014]). The specification describes that TIR-NBS-LIRR proteins are R-proteins providing resistance to a wide array of pathogens and abiotic stress factors and that the LRR domain is involved in protein-protein interaction with the pathogen and assumed to play a key role in providing resistance (paragraph [0014]). The specification describes that position 15-192 of SEQ ID NO: 3 is a TIR domain, positions 209-432 of SEQ ID NO: 3 define an NBS domain, and positions 540-1023 define the LRR domain of SEQ ID NO: 3 (paragraph [0028]). A Raphanus sativus plant comprising the described gene has been deposited under accession number 43737 at NCIMB (paragraph [0035]). The specification describes radish plants that comprise this gene with resistance to 3 isolates of Albugo candida (paragraph [0079-0081], table 3).
Putative radish TIR-NBS-LRR resistance genes have been described in the art, including 21 resistance gene analogs identified from the transcriptome (Wang et al (2017) Scientia Horticulturae. 216: 284-292, published 1/19/2017, hereafter Wang: page 286, right column, paragraph 2-page 287, left column, paragraph 1). Wang also describes that many resistance gene analogs that are nonfunctional pseudogenes exist in plant genomes (page 290, left column, paragraph 1). TIR-NBS-LRR genes are considered to be involved in recognizing “species-specific” pathogens, and the LRR domain exhibits high diversity and has been associated with pathogen recognition (Priyamedha et al (2020) in Brassica Improvement. Wani et al (eds) pages 147-157, available online 3/14/2020, hereafter Priyamedha: Page 149, paragraph 1-page 150, paragraph 1). Priyamedha describes resistance loci for Albugo candida in Brassica crops, including a CC-NB-LRR R gene (page 152, paragraph 4).
Xu et al (2022) Horticulturae. 8. 1164. Published 12/8/2022, after the effective filing date of the instant application; hereafter Xu) describes a total of 187 NBS-LRR genes in radish (abstract). Xu describes that the TIR domain plays a crucial function in pathogen recognition through NADase activity (page 1, paragraph 1). In addition to structural differences, NBS-LRR genes in radish can have tissue-specific expression, which indicates that some NBS-LRR genes play crucial roles in tissue-specific disease resistance (page 9, paragraph 2).
Sequences with at least 95% identity to SEQ ID NO: 2 or 3 are not described in the art, although Engelen et al (WO 2019/178554 filed 3/15/2019) teaches a Brassica napus protein sequence with 61% sequence identity to instant SEQ ID NO: 3 or potentially 74% sequence similarity to the amino acid sequence encoded by instant SEQ ID NO: 2 that provides clubroot resistance in Brassica napus and comprises a Toll-Interleukin receptor domain (Engelen SEQ ID NO: 3, see alignment below; paragraphs [12 & 31]).
Sequence 3, PC/TUS1922601A
GENERAL INFORMATION
APPLICANT: BASF Agricultural Solutions Seed US LLC
TITLE OF INVENTION: Brassica plant resistant to Plasmodiophora brassicae (clubroot)
FILE REFERENCE: BCS18-2008
CURRENT APPLICATION NUMBER: PCT/US19,22601
CURRENT FILING DATE: 2019-03-15
NUMBER OF SEQ ID NOS: 12
SEQ ID NO 3
LENGTH: 1207
TYPE: PRT
ORGANISM: Brassica napus
Instant SEQ ID NO: 3
Query Match 61.7%; Score 3602; Length 1207;
Best Local Similarity 64.9%;
Matches 740; Conservative 111; Mismatches 189; Indels 100; Gaps 11;
Qy 1 MALSLASSSSSSRTWVYDVFPSFSGADVRVTFLSHFRKELDRKLIISFKDNEIERSRSLD 60
|||||||| || |||:||||||||| ||||||||| || |:||| :|||||||||||||
Db 1 MALSLASSPSSCRTWLYDVFPSFSGVDVRVTFLSHLLKEFDKKLITAFKDNEIERSRSLD 60
Qy 61 PELKQAIRDSRIAVVIFSENYASSSWCLNELLEIVKCRDECGQMVIPVFYRLDPSHVRKQ 120
|||||||:||||||||||:||||||||||||||||| ||||||||||||||||||||
Db 61 PELKQAIKDSRIAVVIFSQNYASSSWCLNELLEIVK----CGQMVIPVFYRLDPSHVRKQ 116
Qy 121 TDDFGQIFEKTCHNETEEVKMQWRRALTNVANITGFHSVNWGNEAKMIEEIVSDVLEKLL 180
| |||: ||:||:|:||| |:|||||||:||| |:||||||||| ||||| :|||:|||
Db 117 TGDFGKFFEETCNNKTEEEKIQWRRALTDVANTLGYHSVNWGNEAAMIEEIANDVLDKLL 176
Qy 181 LTPSKDSENFVGIEGHIADLSVLLELELEEVRMVGLWGASGIGKTTIARVLFNRLSRHFQ 240
|| ||||||||||| |:| |||||:|: ||||||||||:||||||||||||| ||||||:
Db 177 LTSSKDSENFVGIEDHVAKLSVLLQLDAEEVRMVGLWGSSGIGKTTIARVLFQRLSRHFR 236
Qy 241 GSIFIDRAFISKSTEVFSRANPGDYSMMLHLQSRFLSKILGKNDIEISQLGELAGRLKHH 300
|||||||||:||: |:| ||| ||:| |||| |||:|||| ||:|: | : |||:
Db 237 GSIFIDRAFVSKTMEIFKAANPDDYNMKLHLQRNFLSEILGKGDIKINHLSAVGERLKNQ 296
Qy 301 KVLIFIDDFNDQVVLDSLVGQTQWFGSGSRIVVVTNDKHHLRSHGIDHIYEVCLPSQKLA 360
|||||||||:|||||::||||||||||||||||||||| :||:|||:|||:||||::|||
Db 297 KVLIFIDDFDDQVVLEALVGQTQWFGSGSRIVVVTNDKQYLRAHGINHIYKVCLPTKKLA 356
Qy 361 VEMFCRSAFNENSPPEGFEVLVAEITRLAGSLPLGLSVLGSSLRGRDKEYWVDLLPTLQT 420
||| ||||| : : ||||| |||::| |||||||||:|||| |||||||||:|||| ||
Db 357 VEMLCRSAFRKKAAPEGFEELVAKVTGLAGSLPLGLNVLGSYLRGRDKEYWMDLLPRLQN 416
Qy 421 GIDGKIERTLKVSYEGLSSKGDKTLFRHIACLFNGEKVTYLKLLLADSDLSVNVGMENLA 480
|:|||||:||:|||:||:|: || ||||||||| ||||||||||||| ||| ||:||||
Db 417 GLDGKIEKTLRVSYDGLTSEEDKALFRHIACLFQWEKVTYLKLLLADSGLSVTVGLENLA 476
Qy 481 DKSLIHVSPWGHVEMHRLLQEMGRSIVRLDEPGTREFLMDSQDICDVLSDGTGTQKILGI 540
||||||| :|:|||||:|||| ||||||| ||||:|:|||||||| ||| |||||
Db 477 DKSLIHVRE-DYVKMHRLLEEMGRRIVRLDEPEKREFLVDAQDICDVLSQDTGTHKILGI 535
Qy 541 SLDTDEIDELHIHENAFTGMRNLRFLKFYSR----YGVGTVKLHIPKSFDYLPLKLKSLC 596
|: ||||||::||||| ||||||||: :|: :| |::|:|::||||| ||| |
Db 536 KLNIDEIDELNVHENAFKGMRNLRFLEIHSQNRHEFGNEEVRIHLPENFDYLPPKLKILD 595
Qy 597 WPRYPMRCLPSTFRPENLTELKMQGSKLEKLWEGVVSLPCLKKMDLSFSHNLIEMPDLSK 656
| |||||||| |||| | :||| |||||||||:||| |||||::| | ||||||||||
Db 596 WYEYPMRCLPSKFRPEKLVKLKMVNSKLEKLWEGIVSLTCLKKMNMSGSQNLIEMPDLSK 655
Qy 657 ATNLETLDLDDCYSLVKLPSSIPHPNKLMRLHLMNCQNLEIIPIGISLKSLEELYLDGCS 716
||||||| |:||:||||||||||||||| | | ||:|:| ||||||||||: | ||||
Db 656 ATNLETLYLEDCFSLVKLPSSIPHPNKLTTLILKNCRNVETIPIGISLKSLKNLRTDGCS 715
Qy 717 RLRNFPQILTNIETINIDETRIEEIPSNLHLEDGRLRELSMQNAKSKKPWERVKPLILLT 776
|:| |||| : || : | | |||||||| | | :| : || ||||: | |||
Db 716 RMRTFPQISSTIEDVYIGATSIEEIPSNLSLCFENLHTFTMHS--PKKLWERVQLLTLLT 773
Qy 777 AIMSPPLKYLYLSDMPTLVELPSSFQNLHQLTHLEITDCINLETLPTGINLRSLDDLYLN 836
|||| | || ||| | ||||||||:||| | ||| :|:||||||||||| || | |
Db 774 TIMSPSLWYLDLSDNPGLVELPSSFKNLHNLRRLEIRNCVNLETLPTGINLGSLKILDLR 833
Qy 837 GCSRLSTFPDISTNIKVLSLIATAIEDVPGSVDKFSVLEELRMERCINLKILPSGINLAS 896
||||
Db 834 GCSR-------------------------------------------------------- 837
Qy 897 LKFLGFSGCPQLSTFPDISTNIEVLYLNETAIEEVPCWVEKFTRLGVLEMKGCNKLKFVS 956
| |||||||:| |||: | |||:|| :|||:||| | | ||| |::|:
Db 838 -----------LRTFPDISTHITHLYLSGTGIEEIPCSIEKFSRLGSLHMNGCNNLEYVN 886
Qy 957 LNISKLKRLGRVELSD--CLNLDQEAL---KTYSDCLLKLSSEEVPSYFIHRTTVTSSFS 1011
||: ||| | |: || ||||||||| |||| | |||| ||||||| |||| || |
Db 887 LNLFKLKHLHEVDFSDCKCLNLDQEALFQKKTYSVCQLKLSGEEVPSYFTHRTTGTS--S 944
Qy 1012 SLTVPLLPSSLSQPFLQFTACLV--HTWDNMSEIDAMPSFTNRFWNSSDSYVQEQDFYG- 1068
|||:||| | :|| ||:| ||:| || | | | | |||| | |||
Db 945 SLTIPLLHSCISQSFLRFRACIVFDSDKDNESYSRCAFRFKGSFRNCSDSYNQAQDFCAV 1004
Qy 1069 -------TCTSDRHMLTLVYYIFLSRDRDILAQMNYTHVDVQLDIKNRSPSEFKEWGIRL 1121
: | :| | | : | :||: :|::: | :: | ||||:
Db 1005 TDDYKIRSYKKDGCLLVLDYQM-----SQIPLEMNFDGLDLKIHIDYCRSAKIKGWGIRI 1059
Instant SEQ ID NO: 2
Length: 1207
Score: 3602.00 Matches: 740
Percent Similarity: 74.6% Conservative: 111
Best Local Similarity: 64.9% Mismatches: 189
Query Match: 61.0% Indels: 100
Gaps: 11
US-18-673-456-2 (1-3384) x PCT-US19-22601A-3 (1-1207)
Qy 1 ATGGCTCTCTCATTAGCTTCTTCTTCTTCCTCTTCTCGCACTTGGGTGTACGATGTTTTC 60
|||||||||||||||||||||||| |||||| |||||||||:::||||||||||||
Db 1 MetAlaLeuSerLeuAlaSerSerProSerSerCysArgThrTrpLeuTyrAspValPhe 20
Qy 61 CCGAGCTTCAGTGGGGCAGACGTCCGTGTTACTTTCCTCAGCCACTTTCGAAAGGAGCTT 120
||||||||||||||| ||||||||||||||||||||||||||| ||||||
Db 21 ProSerPheSerGlyValAspValArgValThrPheLeuSerHisLeuLeuLysGluPhe 40
Qy 121 GACCGGAAACTGATCATTTCTTTCAAAGACAACGAGATAGAGAGAAGCCGGTCACTGGAT 180
|||:::||||||||| :::|||||||||||||||||||||||||||||||||||||||
Db 41 AspLysLysLeuIleThrAlaPheLysAspAsnGluIleGluArgSerArgSerLeuAsp 60
Qy 181 CCAGAGCTTAAACAAGCCATAAGAGATTCGAGGATCGCCGTGGTTATCTTCTCTGAAAAC 240
|||||||||||||||||||||:::||||||||||||||||||||||||||||||:::|||
Db 61 ProGluLeuLysGlnAlaIleLysAspSerArgIleAlaValValIlePheSerGlnAsn 80
Qy 241 TACGCATCTTCAAGCTGGTGTCTAAATGAGTTGCTGGAGATCGTCAAGTGCAGGGATGAG 300
||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 TyrAlaSerSerSerTrpCysLeuAsnGluLeuLeuGluIleValLys------------ 96
Qy 301 TGTGGTCAAATGGTGATACCTGTTTTCTACCGTTTGGATCCTTCCCATGTCAGGAAACAA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 97 CysGlyGlnMetValIleProValPheTyrArgLeuAspProSerHisValArgLysGln 116
Qy 361 ACTGATGACTTTGGACAGATCTTTGAAAAAACATGCCACAACGAAACGGAGGAGGTGAAA 420
||| |||||||||::: ||||||:::||||||:::|||:::||||||||| |||
Db 117 ThrGlyAspPheGlyLysPhePheGluGluThrCysAsnAsnLysThrGluGluGluLys 136
Qy 421 ATGCAATGGAGGAGAGCTTTGACAAATGTAGCTAATATCACCGGATTCCATTCTGTAAAC 480
:::|||||||||||||||||||||:::||||||||| |||:::||||||||||||
Db 137 IleGlnTrpArgArgAlaLeuThrAspValAlaAsnThrLeuGlyTyrHisSerValAsn 156
Qy 481 TGGGGTAACGAAGCAAAAATGATTGAAGAAATTGTCAGTGATGTTTTGGAGAAACTACTT 540
||||||||||||||| ||||||||||||||| :::|||||||||:::|||||||||
Db 157 TrpGlyAsnGluAlaAlaMetIleGluGluIleAlaAsnAspValLeuAspLysLeuLeu 176
Qy 541 TTAACTCCATCGAAGGATTCTGAGAACTTTGTGGGCATCGAAGGTCATATCGCAGATCTG 600
|||||| ||||||||||||||||||||||||||||||||| |||:::||| |||
Db 177 LeuThrSerSerLysAspSerGluAsnPheValGlyIleGluAspHisValAlaLysLeu 196
Qy 601 AGTGTATTGCTGGAGTTGGAATTAGAGGAAGTGAGGATGGTTGGTTTATGGGGTGCTTCA 660
||||||||||||:::|||::: ||||||||||||||||||||||||||||||:::|||
Db 197 SerValLeuLeuGlnLeuAspAlaGluGluValArgMetValGlyLeuTrpGlySerSer 216
Qy 661 GGGATTGGCAAGACTACAATTGCAAGAGTTCTGTTCAACCGACTTTCTCGACACTTTCAA 720
|||||||||||||||||||||||||||||||||||| ||||||||||||||||||:::
Db 217 GlyIleGlyLysThrThrIleAlaArgValLeuPheGlnArgLeuSerArgHisPheArg 236
Qy 721 GGTAGCATTTTCATTGACAGGGCTTTCATATCTAAGAGTACTGAAGTTTTCAGCAGAGCT 780
|||||||||||||||||||||||||||:::||||||::: |||:::||| |||
Db 237 GlySerIlePheIleAspArgAlaPheValSerLysThrMetGluIlePheLysAlaAla 256
Qy 781 AATCCGGGCGACTACAGCATGATGTTGCATTTGCAATCGAGATTCCTATCGAAAATTCTA 840
|||||| ||||||:::||| |||||||||||| |||||||||:::||||||
Db 257 AsnProAspAspTyrAsnMetLysLeuHisLeuGlnArgAsnPheLeuSerGluIleLeu 276
Qy 841 GGGAAAAATGACATAGAGATAAGTCAATTAGGCGAGTTAGCAGGGAGGCTGAAGCACCAT 900
|||||| ||||||:::|||::: ||| ::: |||||||||:::
Db 277 GlyLysGlyAspIleLysIleAsnHisLeuSerAlaValGlyGluArgLeuLysAsnGln 296
Qy 901 AAAGTTCTTATTTTCATTGATGATTTCAACGACCAAGTGGTGCTAGATTCCTTGGTTGGT 960
|||||||||||||||||||||||||||:::|||||||||||||||::::::|||||||||
Db 297 LysValLeuIlePheIleAspAspPheAspAspGlnValValLeuGluAlaLeuValGly 316
Qy 961 CAAACTCAATGGTTTGGAAGTGGGAGCAGAATCGTTGTGGTTACAAATGATAAGCATCAT 1020
|||||||||||||||||||||||||||||||||||||||||||||||||||||| :::
Db 317 GlnThrGlnTrpPheGlySerGlySerArgIleValValValThrAsnAspLysGlnTyr 336
Qy 1021 TTACGATCCCATGGGATTGATCACATTTACGAGGTTTGTCTCCCATCTCAAAAGCTAGCT 1080
||||||:::|||||||||:::|||||||||:::||||||||||||::::::|||||||||
Db 337 LeuArgAlaHisGlyIleAsnHisIleTyrLysValCysLeuProThrLysLysLeuAla 356
Qy 1081 GTTGAGATGTTTTGTCGATCTGCTTTCAACGAAAACTCTCCACCTGAAGGTTTTGAGGTG 1140
||||||||| ||||||||||||||| ::: ::: |||||||||||||||
Db 357 ValGluMetLeuCysArgSerAlaPheArgLysLysAlaAlaProGluGlyPheGluGlu 376
Qy 1141 CTTGTAGCTGAAATTACAAGACTTGCGGGTAGTCTTCCTTTAGGTCTTAGTGTTTTGGGT 1200
|||||||||::::::||| |||||||||||||||||||||||||||:::|||||||||
Db 377 LeuValAlaLysValThrGlyLeuAlaGlySerLeuProLeuGlyLeuAsnValLeuGly 396
Qy 1201 TCATCTCTACGGGGGAGGGATAAAGAGTACTGGGTAGATTTGTTGCCAACGCTTCAGACT 1260
||| |||||||||||||||||||||||||||:::|||||||||||| ||||||
Db 397 SerTyrLeuArgGlyArgAspLysGluTyrTrpMetAspLeuLeuProArgLeuGlnAsn 416
Qy 1261 GGTATAGATGGGAAAATCGAGAGAACATTGAAAGTCAGCTACGAAGGATTAAGTAGCAAA 1320
|||:::|||||||||||||||:::||||||:::|||||||||:::||||||:::|||:::
Db 417 GlyLeuAspGlyLysIleGluLysThrLeuArgValSerTyrAspGlyLeuThrSerGlu 436
Qy 1321 GGAGATAAAACGCTATTTCGACATATCGCATGCCTTTTCAATGGTGAAAAAGTCACATAC 1380
|||||| ||||||||||||||||||||||||||| |||||||||||||||
Db 437 GluAspLysAlaLeuPheArgHisIleAlaCysLeuPheGlnTrpGluLysValThrTyr 456
Qy 1381 CTAAAGTTGTTGCTCGCAGATAGTGACTTGAGTGTTAATGTTGGGATGGAAAACCTAGCT 1440
|||||||||||||||||||||||| ||||||||| ||||||:::||||||||||||
Db 457 LeuLysLeuLeuLeuAlaAspSerGlyLeuSerValThrValGlyLeuGluAsnLeuAla 476
Qy 1441 GATAAGTCCCTCATTCATGTAAGTCCGTGGGGTCATGTGGAGATGCACCGTTTGCTACAA 1500
||||||||||||||||||||| :::|||:::|||||||||||||||:::
Db 477 AspLysSerLeuIleHisValArgGlu---AspTyrValLysMetHisArgLeuLeuGlu 495
Qy 1501 GAGATGGGTAGAAGTATTGTTCGTCTTGACGAGCCTGGGACACGAGAATTTCTTATGGAC 1560
|||||||||||| ||||||||||||||||||||| ||||||||||||:::|||
Db 496 GluMetGlyArgArgIleValArgLeuAspGluProGluLysArgGluPheLeuValAsp 515
Qy 1561 TCACAAGATATATGTGATGTACTCAGTGATGGCACTGGGACTCAAAAGATATTAGGTATA 1620
:::|||||||||||||||||||||||| ||||||||| |||||||||||||||
Db 516 AlaGlnAspIleCysAspValLeuSerGlnAspThrGlyThrHisLysIleLeuGlyIle 535
Qy 1621 TCACTGGACACCGATGAGATTGATGAGTTGCATATACATGAGAACGCCTTCACAGGGATG 1680
|||::: ||||||||||||||||||::::::||||||||||||||| ||||||
Db 536 LysLeuAsnIleAspGluIleAspGluLeuAsnValHisGluAsnAlaPheLysGlyMet 555
Qy 1681 CGTAATCTCCGTTTCCTAAAATTTTACTCGAGA------------TATGGAGTTGGCACA 1728
||||||||||||||||||::: :::|||::: :::|||
Db 556 ArgAsnLeuArgPheLeuGluIleHisSerGlnAsnArgHisGluPheGlyAsnGluGlu 575
Qy 1729 GTGAAATTGCACATACCCAAAAGCTTCGACTATTTGCCGCTTAAACTGAAATCATTGTGT 1788
|||::::::|||:::|||::::::||||||||||||||| ||||||||| |||
Db 576 ValArgIleHisLeuProGluAsnPheAspTyrLeuProProLysLeuLysIleLeuAsp 595
Qy 1789 TGGCCGAGATATCCAATGAGATGTCTTCCTTCTACATTTCGTCCTGAAAACCTCACCGAG 1848
||| |||||||||||||||||||||||| |||||||||||| ||| :::
Db 596 TrpTyrGluTyrProMetArgCysLeuProSerLysPheArgProGluLysLeuValLys 615
Qy 1849 CTTAAAATGCAGGGTAGCAAGCTCGAGAAGCTGTGGGAAGGGGTTGTGTCGCTTCCATGT 1908
||||||||| |||||||||||||||||||||||||||:::||||||||| |||
Db 616 LeuLysMetValAsnSerLysLeuGluLysLeuTrpGluGlyIleValSerLeuThrCys 635
Qy 1909 CTCAAGAAGATGGATTTGAGTTTTTCTCACAACCTGATAGAAATGCCAGATCTTTCAAAG 1968
||||||||||||::::::||| ||| ||||||||||||||||||||||||||||||
Db 636 LeuLysLysMetAsnMetSerGlySerGlnAsnLeuIleGluMetProAspLeuSerLys 655
Qy 1969 GCCACCAATCTGGAGACACTTGATCTTGACGATTGCTATAGTTTGGTGAAGCTTCCTTCC 2028
||||||||||||||||||||| |||:::||||||:::|||||||||||||||||||||
Db 656 AlaThrAsnLeuGluThrLeuTyrLeuGluAspCysPheSerLeuValLysLeuProSer 675
Qy 2029 TCTATCCCACATCCCAACAAACTGATGAGATTGCACCTGATGAATTGTCAAAATCTGGAG 2088
|||||||||||||||||||||||| ||| ||| ||||||:::|||:::|||
Db 676 SerIleProHisProAsnLysLeuThrThrLeuIleLeuLysAsnCysArgAsnValGlu 695
Qy 2089 ATTATTCCAATTGGCATTAGCCTCAAATCTCTCGAAGAGCTATATCTCGATGGATGCTCA 2148
||||||||||||||||||||||||||||||::: ||| ||||||||||||
Db 696 ThrIleProIleGlyIleSerLeuLysSerLeuLysAsnLeuArgThrAspGlyCysSer 715
Qy 2149 CGGTTGAGGAATTTTCCTCAAATCTTAACCAACATCGAAACGATCAATATAGACGAAACA 2208
|||:::||| |||||||||||| ::: |||||| ::: ||| |||
Db 716 ArgMetArgThrPheProGlnIleSerSerThrIleGluAspValTyrIleGlyAlaThr 735
Qy 2209 CGCATTGAAGAAATCCCTTCAAATTTGCATCTGGAGGATGGGCGTCTCAGGGAACTCAGT 2268
|||||||||||||||||||||||| ||| ||| :::
Db 736 SerIleGluGluIleProSerAsnLeuSerLeuCysPheGluAsnLeuHisThrPheThr 755
Qy 2269 ATGCAAAACGCAAAGAGTAAAAAACCATGGGAAAGGGTGAAGCCGCTTATTCTACTCACG 2328
||| ::: |||||| ||||||||||||::: ||| |||||||||
Db 756 MetHisSer------ProLysLysLeuTrpGluArgValGlnLeuLeuThrLeuLeuThr 773
Qy 2329 GCGATCATGTCTCCACCTTTGAAGTATTTGTATCTATCGGATATGCCAACCTTGGTGGAG 2388
|||||||||||| ||| |||||| ||||||||| ||| |||||||||
Db 774 ThrIleMetSerProSerLeuTrpTyrLeuAspLeuSerAspAsnProGlyLeuValGlu 793
Qy 2389 CTCCCTTCTTCATTTCAGAATCTCCATCAACTGACGCATTTGGAAATTACGGACTGCATA 2448
|||||||||||||||:::||||||||| ||| ||||||||| :::|||:::
Db 794 LeuProSerSerPheLysAsnLeuHisAsnLeuArgArgLeuGluIleArgAsnCysVal 813
Qy 2449 AATCTGGAGACTCTTCCCACCGGAATCAACCTCCGTTCTCTCGATGATCTCTATCTCAAT 2508
||||||||||||||||||||||||||||||||| |||||| ||| |||
Db 814 AsnLeuGluThrLeuProThrGlyIleAsnLeuGlySerLeuLysIleLeuAspLeuArg 833
Qy 2509 GGATGCTCAAGGTTGAGTACTTTTCCTGATATCTCAACCAACATCAAAGTCCTCAGCCTA 2568
||||||||||||
Db 834 GlyCysSerArg------------------------------------------------ 837
Qy 2569 ATCGCAACAGCCATTGAAGATGTTCCTGGGTCAGTTGATAAATTCTCTGTGCTTGAAGAG 2628
Db 837 ------------------------------------------------------------ 837
Qy 2629 CTAAGGATGGAAAGATGCATAAATCTGAAGATTCTTCCCTCTGGTATCAACCTCGCATCC 2688
Db 837 ------------------------------------------------------------ 837
Qy 2689 CTCAAATTCTTAGGTTTCAGTGGATGCCCACAGTTGAGTACTTTTCCAGATATCTCTACC 2748
||| |||||||||||||||||||||
Db 838 ---------------------------------LeuArgThrPheProAspIleSerThr 846
Qy 2749 AACATTGAAGTGCTCTATCTAAACGAAACAGCCATTGAAGAGGTTCCTTGTTGGGTTGAG 2808
:::||| |||||||||::: ||| |||||||||:::|||||| :::|||
Db 847 HisIleThrHisLeuTyrLeuSerGlyThrGlyIleGluGluIleProCysSerIleGlu 866
Qy 2809 AAATTCACCAGGCTTGGAGTCTTGGAGATGAAGGGATGCAATAAATTAAAATTTGTAAGC 2868
||||||:::||||||||| ||| ||| ||||||||| |||::::::|||:::
Db 867 LysPheSerArgLeuGlySerLeuHisMetAsnGlyCysAsnAsnLeuGluTyrValAsn 886
Qy 2869 TTAAACATTTCTAAACTCAAACGTCTTGGGAGAGTTGAGTTATCAGAC------TGCTTA 2922
||||||::: ||||||||| ||| |||::: |||||| ||||||
Db 887 LeuAsnLeuPheLysLeuLysHisLeuHisGluValAspPheSerAspCysLysCysLeu 906
Qy 2923 AACTTGGATCAAGAAGCTCTG---------AAAACATATTCAGATTGTCTACTGAAGTTG 2973
||||||||||||||||||||| |||||||||||| ||| |||||||||
Db 907 AsnLeuAspGlnGluAlaLeuPheGlnLysLysThrTyrSerValCysGlnLeuLysLeu 926
Qy 2974 TCAAGTGAAGAAGTGCCTTCATATTTCATTCACCGTACTACGGTAACCTCCTCCTTCTCC 3033
||| ||||||||||||||||||||| |||||||||||| |||||| |||
Db 927 SerGlyGluGluValProSerTyrPheThrHisArgThrThrGlyThrSer------Ser 944
Qy 3034 TCTTTAACCGTCCCTCTACTTCCCAGCTCTCTCTCGCAGCCATTCCTCCAATTCACGGCT 3093
|||||||||:::||||||||| ||| :::|||||| ||||||:::||| |||
Db 945 SerLeuThrIleProLeuLeuHisSerCysIleSerGlnSerPheLeuArgPheArgAla 964
Qy 3094 TGCCTTGTG------CATACTTGGGACAATATGTCAGAAATTGATGCTATGCCTAGTTTT 3147
|||:::||| |||||| ||| |||
Db 965 CysIleValPheAspSerAspLysAspAsnGluSerTyrSerArgCysAlaPheArgPhe 984
Qy 3148 ACAAACAGATTTTGGAACAGCTCTGATTCCTATGTTCAGGAACAAGACTTCTACGGA--- 3204
||| ||| |||||||||||| ||| |||||||||
Db 985 LysGlySerPheArgAsnCysSerAspSerTyrAsnGlnAlaGlnAspPheCysAlaVal 1004
Qy 3205 ---------------------ACATGTACGAGTGATAGGCATATGTTAACATTGGTCTAT 3243
::: ||| :::||| ||| |||
Db 1005 ThrAspAspTyrLysIleArgSerTyrLysLysAspGlyCysLeuLeuValLeuAspTyr 1024
Qy 3244 TATATCTTTCTAAGCAGAGATAGGGATATCCTAGCTCAAATGAACTACACGCATGTCGAT 3303
::: ||| :::||||||::: :::|||
Db 1025 GlnMet---------------SerGlnIleProLeuGluMetAsnPheAspGlyLeuAsp 1039
Qy 3304 GTGCAGCTTGATATTAAGAATCGTAGTCCCTCTGAGTTCAAAGAGTGGGGTATACGACTA 3363
::::::::: ||| :::::: ||| ||||||||||||:::
Db 1040 LeuLysIleHisIleAspTyrCysArgSerAlaLysIleLysGlyTrpGlyIleArgIle 1059
No genes are described in the art that have a coding sequence with 95% sequence identity to instant SEQ ID NO: 2 or that encode an amino acid sequence with 95% sequence to instant SEQ ID NO: 3 or that comprise positions 15 to 195, positions 209 to 432 or a sequence with 95% identity to positions 540 to 1023 of SEQ ID NO: 3. The specification fails to make up for the lack of knowledge on the art.
The structural features that provide resistance to Albugo candida in genes with a coding sequence with 95% identity to SEQ ID NO: 2 or encoding an amino acid sequence with 95% identity to SEQ ID NO: 3 or encoding an amino acid sequence that comprise positions 15 to 195, positions 209 to 432 or a sequence with 95% identity to positions 540 to 1023 of SEQ ID NO: 3 from other proteins with the required sequence identity are not described in the specification.
Hence, Applicant has not, in fact, described nucleic acids that encode a protein that confers resistance to Albugo candida 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.
Claims 2 & 4, drawn to the plant wherein the gene comprises the nucleotide sequence having the coding sequence of SEQ ID NO: 2 or as comprised in the genus of a seed deposited with the NCIMB under NCIMB 43737 are supported by Written Description.
New Matter
Claims 1 & 11-22 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. This is a New Matter rejection.
Claims 1 & 11-22 are drawn to or require a Raphanus sativus plant comprising a gene that comprises a nucleotide sequence from a list of options. Neither the instant specification nor the originally filed claims appear to provide support for the phrase “a nucleotide sequence encoding at least the amino acids at position 15 to position 195 of SEQ ID NO: 3” (option e or v) or “a nucleotide sequence encoding at least the amino acids at position 209 to position 432 of SEQ ID NO: 3” (option f or vi).
Previous claimset option c) required, and the specification paragraph [0030] or [0088] described, a nucleotide sequence encoding at least the amino acids at position 15 to position 192 of SEQ ID NO: 3, the amino acid positions 209 to position 432 of SEQ ID NO: 3, and the amino acid positions 540 to 1023 of SEQ ID NO: 3. The genus of nucleotide sequences encoding all three of these segments is narrower than the amended claims to nucleotide sequences requiring only one of these segments. Furthermore, the prior disclosure is of a nucleotide sequence encoding amino acid positions 15 to 192 not 15 to 195.
Thus, such a concept constitutes NEW MATTER. In response to this rejection, Applicant is required to point to support for the concept or to cancel the new matter.
Although the instant specification or originally filed claims do not specifically recite a nucleotide sequence encoding at least the amino acids at position 540 to position 1023 of SEQ ID NO: 3 (current claim 1, option g), there is support found in the requirement for a nucleotide sequence encoding an LRR domain having at least 95% sequence identity to the amino acids at position 540 to position 1023 of SEQ ID NO: 3 (original claim 1, option d).
Scope of Enablement
Claims 1, 3, & 11-22 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 a gene encoding a protein which confers resistance to Albugo candida wherein the coding sequence of the gene is SEQ ID NO: 2 and the amino acid encoded is SEQ ID NO: 3 and the gene is as comprised in the genome of NCIMB deposit number 43737, does not reasonably provide enablement for any gene with a coding sequence with 95% identity to SEQ ID NO: 2 or encoding an amino acid sequence with 95% identity to SEQ ID NO: 3 or encoding an amino acid sequence that comprise positions 15 to 195, positions 209 to 432 or a sequence with 95% identity to positions 540 to 1023 of SEQ ID NO: 3. 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 the invention commensurate in scope with these claims.
Claims 1, 3, 11-12 & 14-22 are drawn to or require a Raphanus sativus plant comprising a gene encoding a protein conferring resistance to Albugo candida comprising a nucleotide sequence having a coding sequence of at least 95% sequence identity to SEQ ID NO: 2 or encoding a protein having an amino acid sequence of at least 95% sequence identity to SEQ ID NO: 3 or comprising a nucleotide sequence encoding at least the amino acids at position 15 to position 195, position 209 to position 432, or position 540 to position 1023 of SEQ ID NO: 3, or a nucleotide sequence encoding an LRR domain having at least 95% sequence identity to the amino acids at position 540 to 1023 of SEQ ID NO: 3. Claim 13 requires that the gene is introgressed from NCIMB 43737 or from a progeny plant thereof that has retained the gene. Because a progeny plant may have undergone crossing over or spontaneous mutation, a plant encompassed by claim 13 will not necessarily comprise a nucleotide sequence with 100% sequence identity to SEQ ID NO: 2 or encoding an amino acid sequence with 100% identity to instant SEQ ID NO: 3.
Nucleotide sequences encoding a protein having an amino acid sequence of at least 95% sequence identity to the 1128 amino acid-long SEQ ID NO: 3 encompass sequences with 56 substitutions relative to SEQ ID NO: 3. Nucleotide sequences having a coding sequence of at least 95% sequence identity to the 3384 nucleotide-long SEQ ID NO: 2 encompass sequences with 169 substitutions relative to SEQ ID NO: 2, including sequences where every substitution is in a position that results in a different amino acid. This would result in an amino acid sequence with 169 substitutions relative to instant SEQ ID NO: 3, or 85% sequence identity to SEQ ID NO: 3.
A nucleotide sequence encoding an LRR domain having at least 95% sequence identity to the amino acids at position 540 to 1023 of SEQ ID NO: 3 encompasses sequences with 24 substitutions relative to the 483 amino acid long segment. Such a sequence would only need to share 459 amino acids with the 1128 amino acid long protein of SEQ ID NO: 3, or 40% sequence identity. Similarly, a sequence encoding the amino acids at position 15 to position 195 of SEQ ID NO: 3 encompasses sequences that share only 180 amino acids with SEQ ID NO: 3, or 16% identity, and a sequence encoding the amino acids at position 209 to position 432 encompasses sequences that share only 223 amino acids with instant SEQ ID NO: 3, or 19.8% identity.
Moreover, “an” amino acid sequence of SEQ ID NO: 3 encompasses any amino acid sequence of at least two consecutive amino acids found in SEQ ID NO: 3 and “a” coding sequence of SEQ ID NO: 2 encompasses any nucleic acid sequence of at least two consecutive nucleotides found in SEQ ID NO: 2. Therefore, claims 1 & 16-22 encompass any gene conferring resistance to Albugo candida comprising a nucleotide sequence of at least 2 consecutive nucleic acids either found in SEQ ID NO: 2 or capable of encoding 2 consecutive amino acids found in SEQ ID NO: 3.
The instant specification teaches a single example of a genomic nucleic acid sequence (SEQ ID NO: 1) with a single coding sequence (SEQ ID NO: 2) encoding one protein with an amino acid sequence (SEQ ID NO: 3). The instant specification has not taught any variants of the provided nucleic and amino acid sequences that do not have 100% sequence identity to SEQ ID NOs: 1 & 2 or 3 respectively or that comprise positions 15 to 195, 209 to 432 or 540 to 1023 of SEQ ID NO: 3 but do not comprise SEQ ID NO: 3 in its entirety.
The specification teaches that the protein of SEQ ID NO: 3 is a TIR-NBS-LRR protein comprising a Toll/Interleukin-1 receptor (TIR), nucleotide binding site (NBS) domain, and Leucine Rich Repeat (LRR) domain (paragraph [0014]). The specification teaches that TIR-NBS-LIRR proteins are R-proteins providing resistance to a wide array of pathogens and abiotic stress factors and that the LRR domain is involved in protein-protein interaction with the pathogen and assumed to play a key role in providing resistance (paragraph [0014]). The specification teaches that position 15-192 of SEQ ID NO: 3 is a TIR domain, positions 209-432 of SEQ ID NO: 3 define an NBS domain, and positions 540-1023 define the LRR domain of SEQ ID NO: 3 (paragraph [0028]). A Raphanus sativus plant comprising the gene of the invention has been deposited under accession number 43737 at NCIMB (paragraph [0035]). The specification teaches radish plants that comprise this gene with resistance to 3 isolates of Albugo candida (paragraph [0079-0081], table 3).
TIR-NBS-LRR genes are involved in recognizing “species-specific” pathogens, and the LRR domain exhibits high diversity and has been associated with pathogen recognition (Priyamedha et al (2020) in Brassica Improvement. Wani et al (eds) pages 147-157, available online 3/14/2020, hereafter Priyamedha: Page 149, paragraph 1-page 150, paragraph 1). Priyamedha teaches resistance loci for Albugo candida in Brassica crops, including a CC-NB-LRR R gene (page 152, paragraph 4).
Xu et al (2022) Horticulturae. 8. 1164. Published 12/8/2022, after the effective filing date of the instant application; hereafter Xu) teaches a total of 187 NBS-LRR genes in radish (abstract) and teaches that the TIR domain plays a crucial function in pathogen recognition through NADase activity (page 1, paragraph 1). In addition to structural differences, NBS-LRR genes in radish can have tissue-specific expression, which indicates that some NBS-LRR genes play crucial roles in tissue-specific disease resistance (page 9, paragraph 2).
Sequences with at least 95% identity to SEQ ID NO: 2 or 3 are not described in the art, although Engelen et al (WO 2019/178554 filed 3/15/2019) teaches a Brassica napus protein sequence with 61% sequence identity to instant SEQ ID NO: 3 or potentially 74% sequence similarity to the amino acid sequence encoded by instant SEQ ID NO: 2 that provides clubroot resistance in Brassica napus and comprises a Toll-Interleukin receptor domain (Engelen SEQ ID NO: 3, see alignments above; paragraphs [12 & 31]).
Given NBS-LRR genes’ pathogen specific recognition based on the TIR and LRR domains and on expression in specific tissues, and given the lack of guidance in the in instant specification regarding what amino acids or expression profiles may be important in providing Albugo candida resistance, one of ordinary skill in the art would not readily recognize which sequences with 95% identity to SEQ ID NO: 2 or encoding an amino acid sequence with 95% identity to SEQ ID NO: 3 or encoding an amino acid sequence that comprise positions 15 to 195, positions 209 to 432 or a sequence with 95% identity to positions 540 to 1023 of SEQ ID NO: 3, or a sequence found in a progeny of the seeds deposited as NCIMB 43737 would confer the required resistance. One of ordinary skill in the art would be required to conduct undue experimentation to determine which encompassed sequences, if any, provide resistance to Albugo candida. Thus, the instant disclosure does not reasonably enable one of ordinary skill in the art to make the gene of the instant invention over the full scope of claimed genus of sequences.
Claims 2 & 4, drawn to the plant wherein the gene comprises the nucleotide sequence having the coding sequence of SEQ ID NO: 2 or as comprised in the genus of a seed deposited with the NCIMB under NCIMB 43737 are Enabled.
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.
Claim(s) 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Van Andel (US 8,063,271 B2; patented 11/22/2011, hereafter Van Andel).
Claim 19 is drawn to a hybrid seed produced by the method of claim 18, wherein a first Raphanus sativus parent plant is crossed with a second Raphanus sativus parent plant wherein the first or second parent plant comprises in its genome a gene encoding a protein that confers resistance to Albugo candida. Claim 20 is drawn to a plant grown from the hybrid seed.
Van Andel discloses a radish inbred line NIZ-AC2 with resistance to Albugo candida and discloses F1 hybrids between NIZ-AC2 as a male parent and radish hybrids (column 19, lines 12-38 & table 3). Van Andel claim 7 is drawn to a hybrid radish seed produced by crossing a plant of inbred line NIZ-AC2 with a different radish plant and harvesting the resultant seed, and Van Andel claim 8 is drawn to a plant produced by the hybrid radish seed.
Because instant claim 18 encompasses methods wherein the first and/or second parent plant of that comprises the resistance gene may be heterozygous, the hybrid seed of instant claim 19 and the plant of instant claim 20 are not required to comprise a gene encoding a protein that confers resistance to Albugo candida, including a gene with the nucleotide sequences of claim 18 options a)-i). Claims 19-20 are product by process claims, but the process of crossing a first and second heterozygous parent plant will not necessarily result in a hybrid seed product that comprises any one specific gene in the hybrid offspring. Thus, the seed and plant of instant claims 19-20 will not necessarily comprise any distinctive structural characteristics to the final product of another method of crossing between a first and second Raphanus sativus parent plant. See MPEP 2113.
Because the method of instant claim 18 will impart no distinctive structural characteristics to distinguish instant claims 19 & 20, the Raphanus sativus hybrid seed and plant grown from the hybrid seed of Van Andel anticipate instant claims 19 & 20.
Claim Rejections - 35 USC §§ 102, 103
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 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.
Claim(s) 1-4, 11-20 & 22 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Bonnet (1981) Cruciferae Newsletter. No. 6, 60 ref. 2. (available 1/1/1982, hereafter Bonnet).
Claims 1-4, 11-20 & 22 are drawn to a Raphanus sativus plant, seed, propagation material, or a method of selecting or producing such a plant, comprising a gene encoding a protein which confers resistance to Albugo candida wherein the gene comprises a nucleotide sequence encoding a protein having an amino acid sequence of SEQ ID NO: 3.
Bonnet teaches plants of a round scarlet radish variety, Rubiso, with resistance to Albugo candida (page 60, paragraph 2). Bonnet teaches a cross between resistant plant Rubiso 2 and a susceptible line and teaches progeny that are selfed, F1, F2, F3, and backcross 1 generations (page 60, paragraph 3-4). Bonnet teaches that segregation analysis of the progeny of Rubiso 2, which reads on genetic analysis, suggests that the resistance is from a single dominant gene and teachings obtaining homozygous resistant lines (page 60, paragraphs 3-4).
Although the art is silent regarding the presence or absence of a nucleic acid encoding a protein with 95% sequence identity to SEQ ID NO: 3 or having the coding sequence of SEQ ID NO: 2, Rubiso plants with white rust resistance appear to be radish plants within the scope of the claims. The instant specification defines agronomically elite as having a genotype that as a result of human intervention comprises an accumulation of distinguishable and desirable agronomic traits which allow a producer to harvest a product of commercial significance (paragraph [0045]). Under this definition, the white rust resistant Rubiso radish plants of Bonnet read on the Raphanus sativus plant of instant claims 1-3. The white rust resistant plants and their progeny also comprise or make obvious a seed from such a plant or leaves or roots, which read on the seed of claim 14 and the propagation material of claim 15.
Bonnet teaches homozygous resistant lines from selfing Rubiso radish plants, which reads on having the gene homozygously present, instant claim 11. The F1 progeny between Rusbiso and the susceptible line read on a hybrid variety (instant claim 12).
The art is also silent as to whether the resistance gene found in Rubisco is as comprised in the genome of seed deposited under NCIMB 43737, so this plant reads on instant claim 4. Because the process of introgression of claim 13 can be progeny of any generation, the only defining feature of the claimed product is the resistance gene itself. There is no reason why introgression of the single gene from NCIMB 43737 would impart structural characteristics to differentiate the resulting plant from any other introgression history that resulted in a plant with the same resistance gene. So, instant claim 13 is obvious over the Rubisco radish of Bonnet.
The method taught by Bonnet to produce crosses between Rubiso and a susceptible parent and then perform segregation analysis to determine that the resistance is controlled by a single gene reads on a method of instant claim 17, comprising crossing a first parent plant and a second parent plant to obtain an F1 population performing one or more rounds of selfing or crossing with a plant from the F1 population, and selecting from the resulting population a plant that comprises the gene that confers resistance. In order to determine the genetic source of the resistance, Bonnet had to identify, and select, plants that have resistance to perform the analysis. The cross between Rubiso and a susceptible parent also reads on a method for producing hybrid Raphanus sativus seed comprising crossing the first and second parent plant and harvesting the hybrid seed (instant claim 18). The F1 generation plants read on or make obvious the hybrid seed (instant claim 19) and the plant grown from the seed (instant claim 20). The method also reads on a method of claim 22 because introgressing a resistance gene reads on introducing a gene encoding a protein that confers resistance into the genome of the plant to produce a plant exhibiting resistance to Albugo candida.
Because there is no required order to steps in a method claim, Bonnet’s method to determine that resistance is due to a single gene reads on the method of claim 16, comprising selecting a plant that comprises the gene (because Bonnet had to select plants that had resistance and therefore comprised the gene) and identifying by genetic analysis the presence of the gene encoding the protein that confers resistance.
Thus, instant claims 1-4, 11-20 & 22 are anticipated or obvious over Bonnet.
Claim(s) 21 is rejected under 35 U.S.C. 103 as being unpatentable over Bonnet as applied to claims 1-4, 11-20 & 22 above, and further in view of Van Andel (US 8,063,271 B2; patented 11/22/2011, hereafter Van Andel).
Claim 21 is drawn to a method for selecting a plant that is resistant to Albugo candida comprising, identifying by genetic analysis the presence of a gene encoding a protein that confers resistance, selecting a plant that comprises the gene, further testing the selected plant for resistance to Albugo candida, and selecting the further tested plant that exhibits resistance.
Bonnet teaches a method of crossing the Albugo candida resistant Rubisco radish with another parent plant to produce offspring and performing genetic analysis to describe the genetic source of resistance as a single dominant gene.
Bonnet does not teach further testing the selected plant for resistance and selecting the further tested plants that exhibit resistance.
Van Andel teaches a method of backcrossing with a radish line comprising resistance to Albugo candida (Van Andel claim 13), comprising crossing a line with another line, selecting progeny plants that have a desired trait such as disease resistance, crossing the progeny, and selecting backcross progeny that have the desired trait and physiological and morphological characteristics. Van Andel teaches that backcrossing methods may include a test of the progeny to determine if desired characteristics have been transferred, including through genetically associated markers (column 16, lines 20-29). Although Van Andel suggests genetically associated markers are necessary for recessive alleles as opposed to dominant alleles, Van Andel also teaches that backcrossing methods are used in radish and that at the end of backcrossing, transferred genes will be heterozygous. Selfing after the backcross coupled with selection will produce homozygosity for the gene for which the improvement program was undertaken (column 16, lines 42-56).
Before the filing of the instant application, it would have been obvious to one of ordinary skill in the art to modify the method of Bonnet of backcrossing a resistant radish plant and a susceptible line with the method suggested by Van Andel to test progeny with genetic markers as well as screening for disease resistance and further selecting resistant offspring. One of ordinary skill in the art would have been motivated to use both testing for resistance and selecting a plant with the gene identified by genetic analysis, because backcrossed plants will be heterozygous. Testing by phenotype alone will not determine which selfed progeny are homozygous, which is desirable in a backcross program. One of ordinary skill in the art would have had reasonable expectation of success, because backcrossing in radish to incorporate disease resistance traits was routine prior to the filing date of the instant application. Therefore, claims 1-4 & 11-22 are obvious over Bonnet and Van Andel.
Conclusion
No claims are allowed.
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/VICTORIA L DELEO/Examiner, Art Unit 1662
/Anne Kubelik/Primary Examiner, Art Unit 1662
Request for Information under 37 CFR § 1.105
Applicant and the assignee of this application are required under 37 CFR § 1.105 to provide the following information that the examiner has determined is reasonably necessary to the examination of this application.
This request is being made for the following reasons:
Applicant is claiming a Raphanus sativus plant, seed, propagation material, or a method of selecting or producing such a plant, comprising a gene encoding a protein which confers resistance to Albugo candida and which was identified in a source accession of internal denomination 970917 and wherein the gene is as comprised in the genome of seeds of deposit NCIMB 43737, but the instant specification is silent about what starting materials and methods were used to produce Raphanus sativus deposit NCIMB 43737. The requested information is required to make a meaningful and complete search of the prior art.
In response to this requirement, please provide answers to each of the following interrogatories eliciting factual information:
Please supply all of the public or commercial designations/denominations used for the parents of Raphanus sativus deposit NCIMB 43737. Also provide:
Information pertaining to the public availability of the parents of Raphanus sativus deposit NCIMB 43737, especially source accession 970917.
Application or serial numbers of any patent applications or patents in which the instant variety is claimed.
The breeding methodology and history regarding the development of Raphanus sativus deposit NCIMB 43737, such as whether single seed descent, bulk method, backcross method, or some other method was used.
If either of the parents of NCIMB 43737is not publicly available or has no publication, patent application, or patent in which it is claimed, provide the following:
All of the public or commercial designations/denominations used for the parental lines used in making the parents of NCIMB 43737.
Information pertaining to the public availability of the parental lines in making the parents of NCIMB 43737.
The breeding methodology and history regarding the development of the parents of NCIMB 43737, such as whether single seed descent, bulk method, backcross method, or some other method was used.
The filial generation in which the parents of NCIMB 43737 were chosen.
For any parent of the parents of NCIMB 43737 that was obtained from an outside source, please detail that source.
Application or serial numbers of any patent applications or patents in which the parents or sibs of the parents of NCIMB 43737 are claimed.
If Applicant views any or all of the above requested information as a Trade Secret, then Applicant should follow the guidance of MPEP § 724.02 when submitting the requested information. If any part of the response is marked DO NOT SCAN or TRADE SECRET, Applicant is reminded that a cover letter, not so marked, is to be included.
In responding to those requirements that require copies of documents, where the document is a bound text or a single article over 50 pages, the requirement may be met by providing copies of those pages that provide the particular subject matter indicated in the requirement, or where such subject matter is not indicated, the subject matter found in applicant' s disclosure. Please indicate where the relevant information can be found.
The fee and certification requirements of 37 CFR § 1.97 are waived for those documents submitted in reply to this requirement. This waiver extends only to those documents within the scope of this requirement under 37 CFR § 1.105 that are included in the applicant' s first complete communication responding to this requirement. Any supplemental replies subsequent to the first communication responding to this requirement and any information disclosures beyond the scope of this requirement under 37 CFR § 1.105 are subject to the fee and certification requirements of 37 CFR § 1.97 if submitted subsequent to a first Office action on the merits.
The applicant is reminded that the reply to this requirement must be made with candor and good faith under 37 CFR § 1.56. Where the applicant does not have or cannot readily obtain an item of required information, a statement that the item is unknown or cannot be readily obtained may be accepted as a complete reply to the requirement for that item.
This requirement is an attachment of the enclosed Office action. A complete reply to the enclosed Office action must include a complete reply to this requirement. The time period for reply to this requirement coincides with the time period for reply to the enclosed Office action.
/SHUBO (JOE) ZHOU/Supervisory Patent Examiner, Art Units 1661 and 1662
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