DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 6/22/2026 is acknowledged.
Claim 63 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/22/2026.
The restriction is made FINAL.
Status of Claims
Claims 1, 3, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 43, 45-47 & 61-62 are under examination on the merits.
Claim 63 is withdrawn.
Claim Objections
Claims 26, 28, 39, 40, 41 & 45 are objected to because of the following informalities:
Claim 26 (line 2): "comprises" should read --comprising--.
Claim 26 (line 3, line 7) and claim 39 (lines 7-8): "one rust diseases" should read --one rust disease--.
Claim 28 (line 2) and claim 40 (line 2): "and" or another conjunction is needed before "said control plant”.
Claim 41 (line 3): "a" should be inserted before "phenotypically".
Claim 45 (line 10): "NO57" should read --NO: 57-- and "NO59" should read --NO: 59--.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 61-62 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claim(s) recite(s) a DNA construct comprising an isolated polynucleotide encoding an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 1 and further comprising at least one plant compatible expression regulatory element. Claim 62 further requires that the construct comprise a nucleic acid sequence having at least 70% identity to SEQ ID NO: 6 over its entire length.
This judicial exception is not integrated into a practical application because the claim is drawn to a DNA construct, which is a product without markedly different characteristics from a DNA polynucleotide that may be found in nature. The specification describes that the DNA construct can be a plant expression vector and comprise heterologous elements (page 13, lines 28-30) but this is not required by definition. The polynucleotide encoding SEQ ID NO: 1 (SEQ ID NO: 6) was discovered by Applicant as a result of sequencing Aegilops longissima accessions (specification, page 42, line 1-page 43, line 4). Thus, DNA polynucleotides of SEQ ID NO: 6, which read on DNA constructs, are naturally found in Ae. longissima plants.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception, because a plant compatible expression regulatory element encompasses the natural promoters or other regulatory elements that would be found in operable linkage with the coding sequence for the polypeptide of SEQ ID NO: 1 in a naturally occurring plant. The specification specifically describes embodiments wherein the promoter is the natural promoter driving expression of the gene in Ae. longissima (page 6, lines 13-16). Furthermore, an “isolated” but otherwise unchanged polynucleotide lacks markedly different characteristics from a naturally occurring polynucleotide. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977.
Claim Rejections - 35 USC § 112
Indefiniteness
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.
Claims 20, 21, 26, 28, 34-35, 39-41, 43 & 45-47 are 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. All dependent claims are included in the rejections below.
Claim 20 is drawn to the Triticeae plant of claim 1-19, wherein the rust disease is caused by a fungus of the genus Puccinia. Claim 20 and dependent claim 21 are indefinite because they require the material found in canceled claims 2, 4-5, 7-14 & 16-19. In addition, there is insufficient antecedent basis for “the” Triticeae plant of claim 1-19 in claim 20 (line 1), since at least claims 1, 3, 6 & 15 recite plants with different limitations, making each plant distinct. It is indefinite which plant is “the” plant or if all plants of the claims are required.
Claim 45 requires amplifying at least one marker by “a pair comprising SEQ ID NO: 14 and SEQ ID NO: 15; a pair comprising SEQ ID NO: 16 and SEQ ID NO: 17; a pair of primers…” selected from a group. It is unclear if this list represents three distinct pairs of primers and all three are required for the amplification of the at least one marker. Alternatively, claim 45 could be interpreted as requiring just one pair of primers for the amplification of the marker, and SEQ ID NO: 14-15 and SEQ ID NO: 16-17 are options in addition to the Markush group of primer pairs. Because claim 45 has two distinct interpretations, the claim is indefinite.
Claim 26 requires “a corresponding control plant” in line 7 and requires that the Triticeae plant comprising a heterologous polynucleotide has an enhanced tolerance or resistance compared to the control plant. Similarly, claim 39 requires a control Triticeae plant (line 5) that a plant of claim 1 has enhanced resistance when compared to. One of ordinary skill in the art would understand a control plant to be a plant lacking the heterologous polynucleotide. However, claims 28 (depending on claim 26) and claim 40 (depending on claim 39) further require that the control plant is lacking the heterologous polynucleotide and is susceptible to the at least one disease. If claims 28 & 40 require the control plant to lack the heterologous polynucleotide, but claims 26 and 39 do not, then it is unclear what constitutes a control plant. Because the interpretation of “control plant” in claims 26 & 39 is unclear, the evaluation of enhanced resistance compared to said control plant is unclear and the scope of the claim 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, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 43, & 45-47 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, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 43, & 45-47 require a polynucleotide encoding a polypeptide having at least 80% identity to SEQ ID NO: 1 capable of conferring or enhancing tolerance and/or resistance of a Triticeae plant to at least one rust disease. Claim 3 further requires that the polynucleotide comprises a sequence having at least 70% identity to SEQ ID NO: 6. Claims 6, 43, 45 further require that the polynucleotide comprises a sequence having at least 88% identity to SEQ ID NO: 3.
Polynucleotides encoding polypeptides having at least 80% identity to SEQ ID NO: 1 and capable of conferring tolerance to a rust disease in a Triticeae plant are essential to the claimed invention.
Polypeptides with 80% identity to SEQ ID NO: 1 encompass amino acid sequences with 302 substitutions relative to the 1510 amino acid-long SEQ ID NO: 1. Polynucleotides with 70% identity to the 16207-nucleotide long SEQ ID NO: 6 would have 4862 nucleotide substitutions relative to SEQ ID NO: 6, and polynucleotides with 88% identity to the 4533 nucleotide-long SEQ ID NO: 3 would have 543 substitutions relative to SEQ ID NO: 3. Because these nucleic acids encompass those in which substitution occurs across different codons and in which every substitution results in codon that encodes a different amino acid, the recited polynucleotide sequences do not narrow the breadth of encoded amino acid sequences encompassed by the instant invention.
While the claims are drawn to polynucleotides capable of conferring tolerance to a rust disease and encoding a polypeptide with 80% identity to SEQ ID NO: 1, the specification describes only one polypeptide with at least 80% identity to SEQ ID NO: 1: SEQ ID NO: 1. See tables 5 & 6 of the specification. The specification describes two sequences encoding SEQ ID NO: 1, SEQ ID NOs: 3 & 6, and no polynucleotides encoding sequences with as little as 80% identity to SEQ ID NO: 1. The specification additionally provides SEQ ID NO: 68, which comprises both the coding sequence and an endogenous promoter and terminator. Thus, the specification does not describe species over the full scope of the polypeptides, and thus does not describe the full scope of the claimed nucleic acids.
The specification describes the Lr/Yr5458 gene, which encodes SEQ ID NO: 1, as belonging to the family of NLR disease resistance genes (page 21, lines 3-9) but rare because it is the first NLR gene cloned in wheat conferring resistance to two different wheat pathogens (page 32, lines 4-13). The specification describes that tolerance from Lr/Yr5458 does not lead to a hyper-sensitive response but slows down pathogen development and disease progression and is stable across ages, so it is not an adult plant resistance gene (page 32, line 14-25). The specification describes that mechanism of the resistance against two different pathogen species is unclear but proposes that Lr/Yr548 could possibly recognize two alternative effectors or that the rust diseases contain a common effector (page 32, line 26-page 33, line 3). The specification describes domains within the resistance conferring gene, including Rx_N domain, NB-ARC domain, and LRR domains (table 3).
The specification describes that the Lr/Yr548 gene's closest homolog is an uncharacterized RGA2 gene with 87% identity from Ae. tauschii, but that this homolog is not a functional homolog of Lr/Yr548 (page 33, lines 4-12). The specification also describes an RGA2-like putative disease resistance gene from Triticum urartu with 83% identity to SEQ ID NO: 3, but all other predicted genes had less than 80% homology or 80% coverage (page 46, line 4-13; tables 5, 6). The specification describes an Ae. sharonensis resistance gene similar to Lr/Yr548 that has only minor sequence homology and that the CC domain differs from common CC domains (page 49, line 10-page 50, line 9). The instant specification suggests that there is no functional homologue of the Lr/Yr548 gene in current databases (page 49, lines 8-9).
The specification describes constructing a genomic construct comprising artificially shortened exons for transformation as well as a construct comprising cDNA (page 38, line 14-page 39, line 1). Both constructs were introduced into wheat (page 44, line 5-page 45, line 6) and only the gDNA transgene lines had resistance (figure 9). The introns were described to be important for proper gene expression (page 45, lines 4-6), although features of the introns responsible for proper gene expression are not described in the specification.
To summarize, the instant specification describes a Rx_N domain, a NB-ARC domain, and LRR domains as being present in the Lr/Yr5458 gene and that non-coding regions are important for expression of this gene, but the features of the non-coding regions responsible for expression (and the resistant phenotype) and the features of the polypeptide responsible for conferring resistance to two different rust diseases are not described and no functional homologs or homologs with at least 80% identity to SEQ ID NO: 1 are known.
A polynucleotide encoding a polypeptide of instant SEQ ID NO: 1 is known in the art. US 20240218356A1 (published post filing, but with an effective filing date of 5/11/2021) describes a nucleic acid with 99% similarity to instant SEQ ID NO: 3 encoding a protein with 100% similarity to instant SEQ ID NO: 1. See alignments below.
US-18-558-574-26
Sequence 26, US/18558574
Publication No. US20240218356A1
GENERAL INFORMATION
APPLICANT: Two Blades Foundation
APPLICANT: Moscou, Matthew J
APPLICANT: van Esse, Hendrikus P
TITLE OF INVENTION: METHODS FOR PREPARING A LIBRARY OF PLANT DISEASE RESISTANCE GENES
TITLE OF INVENTION: FOR FUNCTIONAL TESTING FOR DISEASE RESISTANCE
FILE REFERENCE: 070294.0225
CURRENT APPLICATION NUMBER: US/18/558,574
CURRENT FILING DATE: 2023-11-02
PRIOR APPLICATION NUMBER: PCT/US2022/028686
PRIOR FILING DATE: 2022-05-11
PRIOR APPLICATION NUMBER: US 63/186,986
PRIOR FILING DATE: 2021-05-11
NUMBER OF SEQ ID NOS: 188
SEQ ID NO 26
LENGTH: 1510
TYPE: PRT
ORGANISM: Aegilops sharonensis
Query Match 100.0%; Score 7946; Length 1510;
Best Local Similarity 100.0%;
Matches 1510; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSGVGEMIASAVVKQITSRLIKLLEDETTMQWKFKGEVDKMAEKMKYLAAVMHDADDKVR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSGVGEMIASAVVKQITSRLIKLLEDETTMQWKFKGEVDKMAEKMKYLAAVMHDADDKVR 60
Qy 61 RGGRVGETVGLWLLKLKSISHDVEDLLDDLDTKNNEAKLKVFFSGNNQAYRWITRPHRLK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RGGRVGETVGLWLLKLKSISHDVEDLLDDLDTKNNEAKLKVFFSGNNQAYRWITRPHRLK 120
Qy 121 DVGKRIEEIKKEGCEFNLDPKAQVEQRQEETYATISATTGMQGRSAEKEKLINLILRSQA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DVGKRIEEIKKEGCEFNLDPKAQVEQRQEETYATISATTGMQGRSAEKEKLINLILRSQA 180
Qy 181 NERISIIPIVGLGGIGKTTLARSVWADEKFNIFDIKAWVHVSDKFDLHKIARTIIRSVDT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 NERISIIPIVGLGGIGKTTLARSVWADEKFNIFDIKAWVHVSDKFDLHKIARTIIRSVDT 240
Qy 241 DINLDSNDLHFLQNILRVKLAGKKYLIFLDDIWEEDGDKLDKLKDMLQHGSNGSRIIITT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 DINLDSNDLHFLQNILRVKLAGKKYLIFLDDIWEEDGDKLDKLKDMLQHGSNGSRIIITT 300
Qy 301 RNQRIVETMSTGILAHERVILPVHESDRIKLGVLPTDDCWELMKIRAFGPDDDQTPLKQI 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RNQRIVETMSTGILAHERVILPVHESDRIKLGVLPTDDCWELMKIRAFGPDDDQTPLKQI 360
Qy 361 GYEIASKCGGIPLVANAFGKVMSGNKSIAAWQYIKDRMVDLGLRDEDQKDTLESLKLSYY 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GYEIASKCGGIPLVANAFGKVMSGNKSIAAWQYIKDRMVDLGLRDEDQKDTLESLKLSYY 420
Qy 421 FMKLEFKICFSYLAAFPKGFIIDTNRLIQQWNALGYIYSEHDGKNCIDYLLGMSFLQISG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FMKLEFKICFSYLAAFPKGFIIDTNRLIQQWNALGYIYSEHDGKNCIDYLLGMSFLQISG 480
Qy 481 PSSASQSPACANASGELTMHDLVHDLALVITVDEFLVLDADATGPRTWKKAIHCRHAELI 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 PSSASQSPACANASGELTMHDLVHDLALVITVDEFLVLDADATGPRTWKKAIHCRHAELI 540
Qy 541 QYKNQSNVFEHLPKKLRSLHIRDSLKWKLPPKAFSRCKYMRVLDLACLVGQLSEGQSTSS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 QYKNQSNVFEHLPKKLRSLHIRDSLKWKLPPKAFSRCKYMRVLDLACLVGQLSEGQSTSS 600
Qy 601 NMRLPRSINKMKLLRYLDATGLPVSSLSKSLHILQNMETLIMSNCSLETLPDNVCSLHKL 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 NMRLPRSINKMKLLRYLDATGLPVSSLSKSLHILQNMETLIMSNCSLETLPDNVCSLHKL 660
Qy 661 SYLDLSGNRSLNKLPTSLGKLSKLSFLNLSGCSVLQGVPKSICQLTCLQYLDMSECRAVQ 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 SYLDLSGNRSLNKLPTSLGKLSKLSFLNLSGCSVLQGVPKSICQLTCLQYLDMSECRAVQ 720
Qy 721 NLPDKFGSLPNISFLNLSGCSKLTKLPDIVNLESLEHFDLSSCHELKDLPQDFGNLQNLV 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 NLPDKFGSLPNISFLNLSGCSKLTKLPDIVNLESLEHFDLSSCHELKDLPQDFGNLQNLV 780
Qy 781 FLSLSDCYKVSVLPESFCQLIHLKYLDLSDCHGLRELPECFGNLSELDSLNLISCSKLQV 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 FLSLSDCYKVSVLPESFCQLIHLKYLDLSDCHGLRELPECFGNLSELDSLNLISCSKLQV 840
Qy 841 LPDSFCSLFKLRHLNLSYCMRLEKLPSSLGDLKLRLLDISAATFHDLPDSIRGMTTLTKL 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 LPDSFCSLFKLRHLNLSYCMRLEKLPSSLGDLKLRLLDISAATFHDLPDSIRGMTTLTKL 900
Qy 901 VVSTAQLGVHNKVRDIRQHLNLPGEIVHTVHLTENKGCSSIVELAQLTCQNLKVLQLQNV 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 VVSTAQLGVHNKVRDIRQHLNLPGEIVHTVHLTENKGCSSIVELAQLTCQNLKVLQLQNV 960
Qy 961 RHPEDAERAKLRDKSDLRVLWLCWGLQREEDIYVLERLVPPRNLEHFTLDGYMSKDFPNW 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 RHPEDAERAKLRDKSDLRVLWLCWGLQREEDIYVLERLVPPRNLEHFTLDGYMSKDFPNW 1020
Qy 1021 ISHISTYLPYLTFLTLCNLGACDNLPPFGQLPNLRCLEMNYIPNITKIGKEFYGEGGTCR 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 ISHISTYLPYLTFLTLCNLGACDNLPPFGQLPNLRCLEMNYIPNITKIGKEFYGEGGTCR 1080
Qy 1081 KLRSIQLKSMENLVEWWTALSGEKNEESLIPNLHCLSIRNCPKLKFLPYPPRSMFWHLDN 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 KLRSIQLKSMENLVEWWTALSGEKNEESLIPNLHCLSIRNCPKLKFLPYPPRSMFWHLDN 1140
Qy 1141 SSMVSPKEGFGKLSSYAFPFLMVVRNCNFAPDKWDWLQHLPTLEIFYVESINGLRALPEA 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 SSMVSPKEGFGKLSSYAFPFLMVVRNCNFAPDKWDWLQHLPTLEIFYVESINGLRALPEA 1200
Qy 1201 MQCLNSLTRLNLWSLKDLEKLPEWLGDLTSLEYIHIKDCPMVTSLPVRMKCLAALRELCL 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 MQCLNSLTRLNLWSLKDLEKLPEWLGDLTSLEYIHIKDCPMVTSLPVRMKCLAALRELCL 1260
Qy 1261 AECRGLEVLPEWLGHLTSLQEFYIMSCPNLTSLPESMKCLTALRVLRLMECEGLEVLPEW 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 AECRGLEVLPEWLGHLTSLQEFYIMSCPNLTSLPESMKCLTALRVLRLMECEGLEVLPEW 1320
Qy 1321 LGHLTSLQEFYIIRCPNLTSLPKSMKCLTALRVLWLTECEGLEVFPEWLGHLISLQEFYI 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 LGHLTSLQEFYIIRCPNLTSLPKSMKCLTALRVLWLTECEGLEVFPEWLGHLISLQEFYI 1380
Qy 1381 TCCSNLTCLPVSMKRLTALRLLWLGQCEGLDVLPEWLGQLISLQEFNIVGCPNLTHFPES 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 TCCSNLTCLPVSMKRLTALRLLWLGQCEGLDVLPEWLGQLISLQEFNIVGCPNLTHFPES 1440
Qy 1441 TRNLTALKKLNIWGCPSLVERCQGEDADLISHIPEVLLEGKTRELWSTSGDAEASTSGAS 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 TRNLTALKKLNIWGCPSLVERCQGEDADLISHIPEVLLEGKTRELWSTSGDAEASTSGAS 1500
Qy 1501 TAEEAGPSTS 1510
||||||||||
Db 1501 TAEEAGPSTS 1510
US-18-558-574-25
Sequence 25, US/18558574
Publication No. US20240218356A1
GENERAL INFORMATION
APPLICANT: Two Blades Foundation
APPLICANT: Moscou, Matthew J
APPLICANT: van Esse, Hendrikus P
TITLE OF INVENTION: METHODS FOR PREPARING A LIBRARY OF PLANT DISEASE RESISTANCE GENES
TITLE OF INVENTION: FOR FUNCTIONAL TESTING FOR DISEASE RESISTANCE
FILE REFERENCE: 070294.0225
CURRENT APPLICATION NUMBER: US/18/558,574
CURRENT FILING DATE: 2023-11-02
PRIOR APPLICATION NUMBER: PCT/US2022/028686
PRIOR FILING DATE: 2022-05-11
PRIOR APPLICATION NUMBER: US 63/186,986
PRIOR FILING DATE: 2021-05-11
NUMBER OF SEQ ID NOS: 188
SEQ ID NO 25
LENGTH: 4530
TYPE: DNA
ORGANISM: Aegilops sharonensis
FEATURE:
NAME/KEY: CDS
LOCATION: (1)..(4530)
Query Match 99.8%; Score 4525.2; Length 4530;
Best Local Similarity 99.9%;
Matches 4527; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 1 ATGAGCGGGGTTGGGGAGATGATCGCGAGTGCCGTGGTGAAGCAAATCACTAGCAGGCTA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGAGCGGGGTTGGGGAGATGATCGCGAGTGCCGTGGTGAAGCAAATCACTAGCAGGCTA 60
Qy 61 ATCAAACTCCTCGAAGATGAGACCACTATGCAGTGGAAGTTTAAAGGCGAGGTGGATAAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ATCAAACTCCTCGAAGATGAGACCACTATGCAGTGGAAGTTTAAAGGCGAGGTGGATAAA 120
Qy 121 ATGGCAGAGAAAATGAAATATCTGGCAGCTGTGATGCATGATGCTGATGATAAAGTGCGC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ATGGCAGAGAAAATGAAATATCTGGCAGCTGTGATGCATGATGCTGATGATAAAGTGCGC 180
Qy 181 CGAGGAGGAAGGGTTGGAGAAACAGTTGGGCTATGGCTCCTGAAATTGAAATCCATCTCC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CGAGGAGGAAGGGTTGGAGAAACAGTTGGGCTATGGCTCCTGAAATTGAAATCCATCTCC 240
Qy 241 CACGACGTTGAGGACCTGCTGGACGACTTGGACACTAAGAATAACGAAGCAAAGCTCAAG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CACGACGTTGAGGACCTGCTGGACGACTTGGACACTAAGAATAACGAAGCAAAGCTCAAG 300
Qy 301 GTATTCTTTTCGGGGAACAATCAAGCTTACCGGTGGATAACTAGGCCCCATCGTTTGAAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GTATTCTTTTCGGGGAACAATCAAGCTTACCGGTGGATAACTAGGCCCCATCGTTTGAAG 360
Qy 361 GACGTGGGGAAGAGAATAGAAGAAATAAAAAAGGAGGGCTGCGAGTTCAATCTGGATCCT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GACGTGGGGAAGAGAATAGAAGAAATAAAAAAGGAGGGCTGCGAGTTCAATCTGGATCCT 420
Qy 421 AAAGCACAAGTCGAACAAAGACAAGAAGAGACTTATGCAACCATCAGCGCGACAACTGGA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 AAAGCACAAGTCGAACAAAGACAAGAAGAGACTTATGCAACCATCAGCGCGACAACTGGA 480
Qy 481 ATGCAAGGGAGGAGCGCTGAAAAAGAAAAATTAATAAATTTGATATTGCGAAGCCAAGCT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 ATGCAAGGGAGGAGCGCTGAAAAAGAAAAATTAATAAATTTGATATTGCGAAGCCAAGCT 540
Qy 541 AATGAGCGTATCTCCATAATTCCAATTGTTGGCCTTGGTGGTATAGGGAAGACAACATTG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 AATGAGCGTATCTCCATAATTCCAATTGTTGGCCTTGGTGGTATAGGGAAGACAACATTG 600
Qy 601 GCTCGGTCAGTTTGGGCAGATGAGAAATTCAACATCTTCGACATCAAAGCCTGGGTTCAT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GCTCGGTCAGTTTGGGCAGATGAGAAATTCAACATCTTCGACATCAAAGCCTGGGTTCAT 660
Qy 661 GTGTCTGACAAGTTTGATTTGCATAAAATTGCGAGAACCATCATCAGAAGCGTAGATACC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GTGTCTGACAAGTTTGATTTGCATAAAATTGCGAGAACCATCATCAGAAGCGTAGATACC 720
Qy 721 GATATCAATCTTGATAGCAATGATTTGCATTTTCTGCAGAATATTCTTCGAGTCAAACTT 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GATATCAATCTTGATAGCAATGATTTGCATTTTCTGCAGAATATTCTTCGAGTCAAACTT 780
Qy 781 GCTGGTAAAAAGTACTTGATTTTTTTGGATGATATCTGGGAAGAAGATGGAGATAAGCTG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GCTGGTAAAAAGTACTTGATTTTTTTGGATGATATCTGGGAAGAAGATGGAGATAAGCTG 840
Qy 841 GACAAGCTGAAGGACATGCTACAGCATGGCTCCAACGGTAGCAGGATTATAATTACTACA 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 GACAAGCTGAAGGACATGCTACAGCATGGCTCCAACGGTAGCAGGATTATAATTACTACA 900
Qy 901 CGTAACCAAAGGATAGTGGAAACAATGAGCACCGGCATTCTTGCACATGAGAGGGTAATT 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 CGTAACCAAAGGATAGTGGAAACAATGAGCACCGGCATTCTTGCACATGAGAGGGTAATT 960
Qy 961 CTCCCGGTGCATGAGTCTGACAGAATCAAATTGGGTGTTCTGCCAACCGATGACTGCTGG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 CTCCCGGTGCATGAGTCTGACAGAATCAAATTGGGTGTTCTGCCAACCGATGACTGCTGG 1020
Qy 1021 GAATTAATGAAGATAAGGGCATTTGGTCCTGATGATGACCAGACTCCTTTGAAACAAATC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GAATTAATGAAGATAAGGGCATTTGGTCCTGATGATGACCAGACTCCTTTGAAACAAATC 1080
Qy 1081 GGGTATGAAATTGCAAGTAAATGTGGGGGTATACCACTCGTGGCAAATGCTTTCGGGAAA 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 GGGTATGAAATTGCAAGTAAATGTGGGGGTATACCACTCGTGGCAAATGCTTTCGGGAAA 1140
Qy 1141 GTAATGTCAGGGAATAAGTCCATCGCAGCATGGCAGTATATAAAAGATAGGATGGTTGAT 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 GTAATGTCAGGGAATAAGTCCATCGCAGCATGGCAGTATATAAAAGATAGGATGGTTGAT 1200
Qy 1201 TTGGGTTTGAGAGACGAAGATCAAAAAGACACATTAGAGTCTCTCAAGTTGAGTTATTAC 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 TTGGGTTTGAGAGACGAAGATCAAAAAGACACATTAGAGTCTCTCAAGTTGAGTTATTAC 1260
Qy 1261 TTCATGAAGCTGGAGTTCAAAATTTGTTTCTCGTATTTGGCGGCATTTCCCAAGGGCTTC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 TTCATGAAGCTGGAGTTCAAAATTTGTTTCTCGTATTTGGCGGCATTTCCCAAGGGCTTC 1320
Qy 1321 ATTATAGACACCAACCGTTTAATCCAGCAATGGAATGCACTTGGATACATTTATTCAGAA 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 ATTATAGACACCAACCGTTTAATCCAGCAATGGAATGCACTTGGATACATTTATTCAGAA 1380
Qy 1381 CATGATGGTAAAAACTGCATCGACTACCTTCTTGGGATGTCCTTTCTTCAGATTTCAGGA 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 CATGATGGTAAAAACTGCATCGACTACCTTCTTGGGATGTCCTTTCTTCAGATTTCAGGA 1440
Qy 1441 CCTTCTTCGGCTAGTCAAAGTCCAGCGTGTGCCAATGCATCTGGGGAGCTTACCATGCAT 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 CCTTCTTCGGCTAGTCAAAGTCCAGCGTGTGCCAATGCATCTGGGGAGCTTACCATGCAT 1500
Qy 1501 GATCTGGTACATGATCTTGCGTTAGTAATTACTGTTGATGAATTCCTTGTTTTGGATGCT 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 GATCTGGTACATGATCTTGCGTTAGTAATTACTGTTGATGAATTCCTTGTTTTGGATGCT 1560
Qy 1561 GATGCTACTGGACCAAGGACTTGGAAAAAAGCTATTCACTGCCGACATGCAGAGTTGATA 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 GATGCTACTGGACCAAGGACTTGGAAAAAAGCTATTCACTGCCGACATGCAGAGTTGATA 1620
Qy 1621 CAATACAAGAATCAATCCAATGTTTTCGAGCATCTGCCAAAAAAGCTTAGATCCCTCCAT 1680
|||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||
Db 1621 CAATACAAGAATCAATCCAATGTTTTCGAGCATCTGCCGAAAAAGCTTAGATCCCTCCAT 1680
Qy 1681 ATTAGAGATTCACTGAAATGGAAACTCCCTCCAAAGGCCTTTTCTCGATGCAAGTACATG 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 ATTAGAGATTCACTGAAATGGAAACTCCCTCCAAAGGCCTTTTCTCGATGCAAGTACATG 1740
Qy 1741 CGTGTCTTGGACCTAGCATGTTTAGTAGGGCAACTCTCTGAAGGGCAATCAACGTCAAGC 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 CGTGTCTTGGACCTAGCATGTTTAGTAGGGCAACTCTCTGAAGGGCAATCAACGTCAAGC 1800
Qy 1801 AACATGAGGCTGCCACGTTCCATAAACAAAATGAAGCTACTTAGGTACCTTGATGCCACG 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 AACATGAGGCTGCCACGTTCCATAAACAAAATGAAGCTACTTAGGTACCTTGATGCCACG 1860
Qy 1861 GGATTGCCAGTTTCTTCACTTTCTAAGTCTTTGCATATACTTCAAAATATGGAAACTCTG 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1861 GGATTGCCAGTTTCTTCACTTTCTAAGTCTTTGCATATACTTCAAAATATGGAAACTCTG 1920
Qy 1921 ATAATGTCCAATTGCTCACTTGAAACCTTGCCTGACAATGTTTGTAGCCTCCACAAACTT 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1921 ATAATGTCCAATTGCTCACTTGAAACCTTGCCTGACAATGTTTGTAGCCTCCACAAACTT 1980
Qy 1981 AGCTATCTTGATCTGTCCGGTAATAGAAGCCTTAATAAGCTACCTACGTCGTTGGGCAAG 2040
|||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||
Db 1981 AGCTATCTTGATCTGTCCGGTAATAGAAGCCTTAATAAGCTACCTACGTCGTTGGGTAAG 2040
Qy 2041 CTCTCTAAGCTCTCTTTCCTCAACTTATCAGGGTGTTCCGTCCTCCAAGGGGTGCCTAAA 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2041 CTCTCTAAGCTCTCTTTCCTCAACTTATCAGGGTGTTCCGTCCTCCAAGGGGTGCCTAAA 2100
Qy 2101 TCCATTTGCCAGTTGACATGTTTACAATACCTAGACATGTCAGAGTGTCGTGCCGTTCAA 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2101 TCCATTTGCCAGTTGACATGTTTACAATACCTAGACATGTCAGAGTGTCGTGCCGTTCAA 2160
Qy 2161 AATCTTCCTGATAAGTTTGGTAGCCTACCAAATATCTCATTCCTAAATTTGTCCGGTTGC 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2161 AATCTTCCTGATAAGTTTGGTAGCCTACCAAATATCTCATTCCTAAATTTGTCCGGTTGC 2220
Qy 2221 TCAAAATTAACCAAACTACCTGACATTGTTAACCTTGAGTCTTTGGAGCATTTCGACCTA 2280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2221 TCAAAATTAACCAAACTACCTGACATTGTTAACCTTGAGTCTTTGGAGCATTTCGACCTA 2280
Qy 2281 TCAAGTTGCCACGAGCTAAAAGACCTCCCACAAGATTTTGGTAATCTTCAAAATCTTGTG 2340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2281 TCAAGTTGCCACGAGCTAAAAGACCTCCCACAAGATTTTGGTAATCTTCAAAATCTTGTG 2340
Qy 2341 TTCTTGAGCCTCTCTGATTGCTACAAGGTTTCAGTGCTCCCGGAATCATTTTGCCAGCTT 2400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2341 TTCTTGAGCCTCTCTGATTGCTACAAGGTTTCAGTGCTCCCGGAATCATTTTGCCAGCTT 2400
Qy 2401 ATTCATTTGAAATACCTAGATCTTTCAGATTGCCATGGCCTCAGGGAACTCCCAGAGTGT 2460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2401 ATTCATTTGAAATACCTAGATCTTTCAGATTGCCATGGCCTCAGGGAACTCCCAGAGTGT 2460
Qy 2461 TTTGGTAACCTTTCTGAGCTTGACTCATTGAACCTAATAAGTTGTTCCAAGCTGCAAGTA 2520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2461 TTTGGTAACCTTTCTGAGCTTGACTCATTGAACCTAATAAGTTGTTCCAAGCTGCAAGTA 2520
Qy 2521 CTGCCTGACTCATTCTGTAGCTTGTTTAAGCTGAGGCATCTCAATTTGTCATACTGTATG 2580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2521 CTGCCTGACTCATTCTGTAGCTTGTTTAAGCTGAGGCATCTCAATTTGTCATACTGTATG 2580
Qy 2581 AGGCTTGAAAAGCTCCCATCCTCGTTAGGTGACCTTAAGCTTCGGTTATTGGACATCTCT 2640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2581 AGGCTTGAAAAGCTCCCATCCTCGTTAGGTGACCTTAAGCTTCGGTTATTGGACATCTCT 2640
Qy 2641 GCTGCAACTTTCCATGATTTACCGGATAGCATCCGTGGCATGACTACACTCACTAAACTT 2700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2641 GCTGCAACTTTCCATGATTTACCGGATAGCATCCGTGGCATGACTACACTCACTAAACTT 2700
Qy 2701 GTGGTCTCGACAGCACAACTAGGGGTTCATAACAAGGTTCGTGACATTCGGCAGCATCTG 2760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2701 GTGGTCTCGACAGCACAACTAGGGGTTCATAACAAGGTTCGTGACATTCGGCAGCATCTG 2760
Qy 2761 AATTTGCCAGGGGAGATAGTACATACTGTACATCTGACTGAAAACAAAGGATGTAGCAGT 2820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2761 AATTTGCCAGGGGAGATAGTACATACTGTACATCTGACTGAAAACAAAGGATGTAGCAGT 2820
Qy 2821 ATTGTAGAGTTAGCACAATTGACCTGTCAAAACTTGAAAGTCTTACAACTTCAGAATGTC 2880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2821 ATTGTAGAGTTAGCACAATTGACCTGTCAAAACTTGAAAGTCTTACAACTTCAGAATGTC 2880
Qy 2881 AGGCATCCGGAAGATGCAGAGAGAGCCAAGTTACGTGATAAATCAGATCTTCGGGTTCTA 2940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2881 AGGCATCCGGAAGATGCAGAGAGAGCCAAGTTACGTGATAAATCAGATCTTCGGGTTCTA 2940
Qy 2941 TGGCTTTGTTGGGGACTCCAGCGAGAAGAGGATATTTATGTGCTGGAGAGGCTTGTACCT 3000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2941 TGGCTTTGTTGGGGACTCCAGCGAGAAGAGGATATTTATGTGCTGGAGAGGCTTGTACCT 3000
Qy 3001 CCACGCAATCTTGAACATTTTACGCTAGATGGGTATATGAGCAAGGATTTCCCTAACTGG 3060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3001 CCACGCAATCTTGAACATTTTACGCTAGATGGGTATATGAGCAAGGATTTCCCTAACTGG 3060
Qy 3061 ATTTCTCACATCTCCACATACCTTCCTTATCTCACCTTTCTCACCCTTTGCAATTTAGGA 3120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3061 ATTTCTCACATCTCCACATACCTTCCTTATCTCACCTTTCTCACCCTTTGCAATTTAGGA 3120
Qy 3121 GCATGTGATAATCTTCCACCATTTGGGCAACTGCCAAATTTAAGATGTCTAGAGATGAAT 3180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3121 GCATGTGATAATCTTCCACCATTTGGGCAACTGCCAAATTTAAGATGTCTAGAGATGAAT 3180
Qy 3181 TATATTCCTAACATCACAAAAATTGGCAAGGAATTCTATGGAGAAGGTGGAACCTGTAGG 3240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3181 TATATTCCTAACATCACAAAAATTGGCAAGGAATTCTATGGAGAAGGTGGAACCTGTAGG 3240
Qy 3241 AAATTAAGAAGTATACAATTGAAGTCAATGGAGAATTTGGTGGAATGGTGGACTGCACTC 3300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3241 AAATTAAGAAGTATACAATTGAAGTCAATGGAGAATTTGGTGGAATGGTGGACTGCACTC 3300
Qy 3301 TCAGGTGAGAAAAATGAAGAGTCACTGATCCCTAATTTGCATTGTTTGTCAATAAGGAAC 3360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3301 TCAGGTGAGAAAAATGAAGAGTCACTGATCCCTAATTTGCATTGTTTGTCAATAAGGAAC 3360
Qy 3361 TGCCCCAAGTTGAAGTTCCTACCATATCCCCCGAGGAGTATGTTTTGGCACTTGGATAAT 3420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3361 TGCCCCAAGTTGAAGTTCCTACCATATCCCCCGAGGAGTATGTTTTGGCACTTGGATAAT 3420
Qy 3421 AGCAGCATGGTTTCGCCAAAAGAGGGATTTGGAAAGCTTTCTTCTTACGCTTTTCCTTTT 3480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3421 AGCAGCATGGTTTCGCCAAAAGAGGGATTTGGAAAGCTTTCTTCTTACGCTTTTCCTTTT 3480
Qy 3481 CTCATGGTAGTAAGAAACTGCAACTTTGCTCCAGACAAATGGGATTGGCTTCAACACCTC 3540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3481 CTCATGGTAGTAAGAAACTGCAACTTTGCTCCAGACAAATGGGATTGGCTTCAACACCTC 3540
Qy 3541 CCCACCCTTGAGATATTTTATGTTGAGAGCATCAATGGCTTGAGGGCATTGCCAGAGGCC 3600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3541 CCCACCCTTGAGATATTTTATGTTGAGAGCATCAATGGCTTGAGGGCATTGCCAGAGGCC 3600
Qy 3601 ATGCAATGTTTAAACTCTCTCACAAGACTAAATTTGTGGTCATTAAAGGACCTGGAGAAA 3660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3601 ATGCAATGTTTAAACTCTCTCACAAGACTAAATTTGTGGTCATTAAAGGACCTGGAGAAA 3660
Qy 3661 CTGCCAGAATGGTTGGGGGACCTCACTTCTCTAGAATACATTCACATCAAAGATTGTCCC 3720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3661 CTGCCAGAATGGTTGGGGGACCTCACTTCTCTAGAATACATTCACATCAAAGATTGTCCC 3720
Qy 3721 ATGGTGACATCTTTGCCTGTAAGAATGAAGTGTCTTGCTGCTCTTAGAGAACTTTGCCTG 3780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3721 ATGGTGACATCTTTGCCTGTAAGAATGAAGTGTCTTGCTGCTCTTAGAGAACTTTGCCTG 3780
Qy 3781 GCGGAGTGCAGAGGCCTAGAAGTATTGCCAGAATGGCTGGGACATCTGACTTCCCTACAA 3840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3781 GCGGAGTGCAGAGGCCTAGAAGTATTGCCAGAATGGCTGGGACATCTGACTTCCCTACAA 3840
Qy 3841 GAGTTCTATATCATGAGTTGCCCCAACCTGACTTCTTTGCCTGAAAGCATGAAGTGTCTT 3900
||||||||||||||||||||||||||||||||||| ||||||||||||||||||||||||
Db 3841 GAGTTCTATATCATGAGTTGCCCCAACCTGACTTCCTTGCCTGAAAGCATGAAGTGTCTT 3900
Qy 3901 ACTGCTCTCAGAGTACTTCGGCTGATGGAGTGCGAAGGCCTAGAAGTATTGCCAGAATGG 3960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3901 ACTGCTCTCAGAGTACTTCGGCTGATGGAGTGCGAAGGCCTAGAAGTATTGCCAGAATGG 3960
Qy 3961 CTGGGACATCTCACTTCCCTACAAGAGTTCTATATCATCCGTTGCCCCAACCTGACTTCT 4020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3961 CTGGGACATCTCACTTCCCTACAAGAGTTCTATATCATCCGTTGCCCCAACCTGACTTCT 4020
Qy 4021 TTGCCTAAAAGCATGAAGTGTCTTACTGCTCTCAGAGTACTTTGGCTGACGGAGTGCGAA 4080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4021 TTGCCTAAAAGCATGAAGTGTCTTACTGCTCTCAGAGTACTTTGGCTGACGGAGTGCGAA 4080
Qy 4081 GGCCTAGAAGTATTCCCAGAATGGCTAGGACATCTCATTTCCCTACAAGAGTTTTACATC 4140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4081 GGCCTAGAAGTATTCCCAGAATGGCTAGGACATCTCATTTCCCTACAAGAGTTTTACATC 4140
Qy 4141 ACCTGTTGCTCCAACCTGACTTGTTTGCCTGTAAGCATGAAGCGTCTTACTGCTCTGAGA 4200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4141 ACCTGTTGCTCCAACCTGACTTGTTTGCCTGTAAGCATGAAGCGTCTTACTGCTCTGAGA 4200
Qy 4201 TTACTCTGGTTGGGCCAGTGTGAAGGTCTAGACGTATTGCCAGAATGGTTGGGACAGCTC 4260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4201 TTACTCTGGTTGGGCCAGTGTGAAGGTCTAGACGTATTGCCAGAATGGTTGGGACAGCTC 4260
Qy 4261 ATCTCCCTTCAAGAATTTAACATCGTCGGTTGCCCGAACTTGACACATTTTCCTGAAAGC 4320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4261 ATCTCCCTTCAAGAATTTAACATCGTCGGTTGCCCGAACTTGACACATTTTCCTGAAAGC 4320
Qy 4321 ACACGGAACCTTACCGCCTTGAAGAAACTGAATATTTGGGGATGTCCGAGTCTTGTTGAG 4380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4321 ACACGGAACCTTACCGCCTTGAAGAAACTGAATATTTGGGGATGTCCGAGTCTTGTTGAG 4380
Qy 4381 AGGTGCCAAGGGGAGGATGCTGACCTGATTTCTCATATCCCGGAAGTCTTGTTAGAAGGA 4440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4381 AGGTGCCAAGGGGAGGATGCTGACCTGATTTCTCATATCCCGGAAGTCTTGTTAGAAGGA 4440
Qy 4441 AAAACTAGAGAATTGTGGTCGACTTCCGGAGATGCTGAAGCATCGACTTCCGGAGCATCG 4500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4441 AAAACTAGAGAATTGTGGTCGACTTCCGGAGATGCTGAAGCATCGACTTCCGGAGCATCG 4500
Qy 4501 ACTGCTGAAGAAGCTGGACCATCGACTTCT 4530
||||||||||||||||||||||||||||||
Db 4501 ACTGCTGAAGAAGCTGGACCATCGACTTCT 4530
Other than this identical protein, the polypeptides described in the art are less than 80% similar to instant SEQ ID NO: 1. UniProt record A0ACD5WJ07_AVESA (available 1/28/2026) describes an uncharacterized protein in oat with 68.7% sequence identity to instant SEQ ID NO: 1. See alignment below.
A0ACD5WJ07_AVESA
ID A0ACD5WJ07_AVESA Unreviewed; 1354 AA.
AC A0ACD5WJ07;
DT 28-JAN-2026, integrated into UniProtKB/TrEMBL.
DT 28-JAN-2026, sequence version 1.
DT 28-JAN-2026, entry version 1.
DE SubName: Full=Uncharacterized protein {ECO:0000313|EnsemblPlants:AVESA.00010b.r2.4AG0647040.2.CDS};
OS Avena sativa (Oat).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; Liliopsida; Poales; Poaceae; BOP clade;
OC Pooideae; Poodae; Poeae; Poeae Chloroplast Group 1 (Aveneae type);
OC Aveninae; Avena.
OX NCBI_TaxID=4498 {ECO:0000313|EnsemblPlants:AVESA.00010b.r2.4AG0647040.2.CDS, ECO:0000313|Proteomes:UP001732700};
RN [1] {ECO:0000313|EnsemblPlants:AVESA.00010b.r2.4AG0647040.2.CDS}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Scholz U., Mascher M., Fiebig A.;
RL Submitted (MAY-2021) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|EnsemblPlants:AVESA.00010b.r2.4AG0647040.2.CDS}
RP IDENTIFICATION.
RG EnsemblPlants;
RL Submitted (SEP-2025) to UniProtKB.
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DR EnsemblPlants; AVESA.00010b.r2.4AG0647040.2; AVESA.00010b.r2.4AG0647040.2.CDS; AVESA.00010b.r2.4AG0647040.
DR Proteomes; UP001732700; Chromosome 4A.
PE 4: Predicted;
KW Reference proteome {ECO:0000313|Proteomes:UP001732700}.
SQ SEQUENCE 1354 AA; 153531 MW; A22902E698BEFFE8 CRC64;
Query Match 68.7%; Score 5462.5; Length 1354;
Best Local Similarity 71.2%;
Matches 1059; Conservative 132; Mismatches 148; Indels 149; Gaps 4;
Qy 1 MSGVGEMIASAVVKQITSRLIKLLEDETTMQWKFKGEVDKMAEKMKYLAAVMHDADDKVR 60
| |||||||||:||||||||||: || ::||||||||||||||||||||||||||:|||
Db 1 MVGVGEMIASAMVKQITSRLIKIAGDEISLQWKFKGEVDKMAEKMKYLAAVMHDADNKVR 60
Qy 61 RGGRVGETVGLWLLKLKSISHDVEDLLDDLDTKNNEAKLKVFFSGNNQAYRWITRPHRLK 120
||| |||||||||:|||||:|:||||||||:||||||||:||| |||||:|||||| |:
Db 61 RGGIHGETVGLWLLQLKSISYDIEDLLDDLDSKNNEAKLKIFFSRNNQAYQWITRPHNLE 120
Qy 121 DVGKRIEEIKKEGCEFNLDPKAQVEQ-RQEETYATIS---ATTGMQGRSAEKEKLINLIL 176
||||||||:| || |||||:|:||| :: :|:| || ||||||||||:||| |:|
Db 121 DVGKRIEELKNEGKAFNLDPEARVEQSKKNDTFAAISDGGTKTGMQGRSAEKDKLIRLLL 180
Qy 177 RSQANERISIIPIVGLGGIGKTTLARSVWADEKFNIFDIKAWVHVSDKFDLHKIARTIIR 236
|::||||||||||||||||||||||:||:||:: |:|||:||||||||||| || |||||
Db 181 RTEANERISIIPIVGLGGIGKTTLAQSVYADKRVNVFDIQAWVHVSDKFDLRKIVRTIIR 240
Qy 237 SVDTDINLDSNDLHFLQNILRVKLAGKKYLIFLDDIWEEDGDKLDKLKDMLQHGSNGSRI 296
||| :||||:: || |||:| | |||||| ||| |||||| |::|| |||||||||||
Db 241 SVDININLDTSHKQFLHNILQVTLTGKKYLIVLDDFWEEDGDNLEELKQMLQHGSNGSRI 300
Qy 297 IITTRNQRIVETMSTGILAHERVILPVHESDRIKLGVLPTDDCWELMKIRAFGPDDDQTP 356
::||| | :||||||| |||:|||||| |||:| |||||||||||||||||||| |||||
Db 301 VVTTRKQSVVETMSTGDLAHQRVILPVCESDQINLGVLPTDDCWELMKIRAFGPHDDQTP 360
Qy 357 LKQIGYEIASKCGGIPLVANAFGKVMSGNKSIAAWQYIKDRMVDLGLRDEDQKDTLESLK 416
||||||||||||||||||||| |||||||||: ||| || |||||||| | |||||||||
Db 361 LKQIGYEIASKCGGIPLVANALGKVMSGNKSVGAWQDIKLRMVDLGLRGEHQKDTLESLK 420
Qy 417 LSYYFMKLEFKICFSYLAAFPKGFIIDTNRLIQQWNALGYIYSEHDGKNCIDYLLGMSFL 476
||||:|||||||||:| |||||||||||||||||||||||||||||::|||||||||||
Db 421 LSYYYMKLEFKICFAYFVAFPKGFIIDTNRLIQQWNALGYIYSEHDGRSCIDYLLGMSFL 480
Qy 477 QISGPSSASQSPACANASGELTMHDLVHDLALVITVDEFLVLDADATGPRTWKKAIHCRH 536
||||| |||| | ::|| :|:||||||||| :|| |||:|||||:| |||||||||||
Db 481 QISGPPSASQRPMRSSASRKLSMHDLVHDLASIITGDEFVVLDADSTELRTWKKAIHCRH 540
Qy 537 AELIQYKNQSNVFEHLPKKLRSLHIRDSLKWKLPPKAFSRCKYMRVLDLACLVGQLSEGQ 596
|||||||||||||||||||||||||||| :|:|||||||: ||||||||:| ||||||||
Db 541 AELIQYKNQSNVFEHLPKKLRSLHIRDSQRWQLPPKAFSQSKYMRVLDLSCSVGQLSEGQ 600
Qy 597 STSSNMRLPRSINKMKLLRYLDATGLPVSSLSKSLHILQNMETLIMSNCSLETLPDNVCS 656
|||||:||| || ||||||||||||||| |||||: |||||||||||| |: |||::|:
Db 601 STSSNIRLPCSIKKMKLLRYLDATGLPVPSLSKSVCTLQNMETLIMSNCLLDILPDDICN 660
Qy 657 LHKLSYLDLSGNRSLNKLPTSLGKLSKLSFLNLSGCSVLQGVPKSICQLTCLQYLDMSEC 716
|||| |||||||||| ||| |||||||||||||||||:|| ||||||||||||::|||||
Db 661 LHKLCYLDLSGNRSLIKLPASLGKLSKLSFLNLSGCSILQDVPKSICQLTCLQHIDMSEC 720
Qy 717 RAVQNLPDKFGSLPNISFLNLSGCSKLTKLPDIVNLESLEHFDLSSCHELKDLPQDFGNL 776
||: |||||||||||| ||||||||||||||| |||| ||| ||||||||::||||||||
Db 721 RAIHNLPDKFGSLPNILFLNLSGCSKLTKLPDSVNLEYLEHLDLSSCHELENLPQDFGNL 780
Qy 777 QNLVFLSLSDCYKVSVLPESFCQLIHLKYLDLSDCHGLRELPECFGNLSELDSLNLISCS 836
::||||:||||||||||||||||||||| ||||||| | |||:||||||||||||| |||
Db 781 RSLVFLNLSDCYKVSVLPESFCQLIHLKDLDLSDCHNLSELPDCFGNLSELDSLNLTSCS 840
Qy 837 KLQVLPDSFCSLFKLRHLNLSYCMRLEKLPSSLGDLKLRLLDISAATFHDLPDSIRGMTT 896
|||:||:||| ||||||||||||||||||| || |||:|||:|: ||||||||: |:||
Db 841 KLQLLPESFCKLFKLRHLNLSYCMRLEKLPPSLDGLKLQLLDLSSVTFHDLPDSLHGITT 900
Qy 897 LTKLVVSTAQLGVHNKVRDIRQHLNLPGEIVHTVHLTENKGCSSIVELAQLTCQNLKVLQ 956
||:|||::|: |::: ||||: ||| | |||||| ||||||||||||:| |: |:||:
Db 901 LTQLVVTSARKKVYDQARDIRKRLNLAGMIVHTVHQIENKGCSSIVELAELACEELQVLR 960
Qy 957 LQNVRHPEDAERAKLRDKSDLRVLWLCWGLQREEDIYVLERLVPPRNLEHFTLDGYMSKD 1016
| |||:||||||||||||:|||:| | |||| ||| |||||:||| |||| | |||:||
Db 961 LYNVRYPEDAERAKLRDKTDLRLLNLRWGLQGEEDKSVLERLIPPRTLEHFFLSGYMNKD 1020
Qy 1017 FPNWISHISTYLPYLTFLTLCNLGACDNLPPFGQLPNLRCLEMNYIPNITKIGKEFYGEG 1076
||||:|||||||| ||:| | :|| || ||| | ||||| | | |||: || |||| |
Db 1021 FPNWMSHISTYLPSLTYLRLSDLGTCDMLPPVGGLPNLRSLVMQNIPNLRKIVTEFYGVG 1080
Qy 1077 G-TCRKLRSIQLKSMENLVEWWTALSGEKNEESLIPNLHCLSIRNCPKLKFLPYPPRSMF 1135
| || |||:|||:|||||||||| ||||:||| |||||| | |::|||||||||||||||
Db 1081 GETCTKLRTIQLESMENLVEWWTTLSGEENEEFLIPNLHSLEIKDCPKLKFLPYPPRSMF 1140
Qy 1136 WHLDNSSMVSPKEGFGKLSSYAFPFLMVVRNCNFAPDKWDWLQHLPTLEIFYVESINGLR 1195
| |::|:|| |||||||||| | || |||:|||||| ||| ||||||||||:|:| ||||
Db 1141 WRLNDSNMVLPKEGFGKLSSSALPFEMVVKNCNFAPHKWDRLQHLPTLEIFHVDSCNGLR 1200
Qy 1196 ALPEAMQCLNSLTRLNLWSLKDLEKLPEWLGDLTSLEYIHIKDCPMVTSLPVRMKCLAAL 1255
|||| :|| |||:| ||::|||: ||| ||:|||||:| ::|||:|||
Db 1201 ALPEVFRCLTSLTKLYLWAMKDLDTLPECLGNLTSLEHISMEDCPLVTS----------- 1249
Qy 1256 RELCLAECRGLEVLPEWLGHLTSLQEFYIMSCPNLTSLPESMKCLTALRVLRLMECEGLE 1315
Db 1250 ------------------------------------------------------------ 1249
Qy 1316 VLPEWLGHLTSLQEFYIIRCPNLTSLPKSMKCLTALRVLWLTECEGLEVFPEWLGHLISL 1375
Db 1250 ------------------------------------------------------------ 1249
Qy 1376 QEFYITCCSNLTCLPVSMKRLTALRLLWLGQCEGLDVLPEWLGQLISLQEFNIVGCPNLT 1435
|| |||:|||||:||| :| ||:|||||||:||||:||:|| |||||
Db 1250 -------------LPESMKKLTALRVLWLKECIGLEVLPEWLGELISLEEFSIVCCPNLT 1296
Qy 1436 HFPESTRNLTALKKLNIWGCPSLVERCQGEDADLISHIPEVLLEGKTR 1483
: ||: |||||||:| |||||||||||||||| :||||||| | | |
Db 1297 YLPETVRNLTALKELYIWGCPSLVERCQGEDATMISHIPEVTLYGSRR 1344
NLR resistance genes are described in the art. Li et al (2015) Current Opinion in Immunology. 32:114–121 (published 2/6/2015, hereafter Li) describes that most plant R genes encode NLR proteins, and that NLR protein family in plants often comprise hundreds of members (page 114, left column, paragraph 1-right column, paragraph 1). Li describes that NLR proteins generally follow a gene-for-gene pattern with a specific effector for recognition, and that while plant NLRs can recognize effectors directly through protein-protein interaction, most often they interact with host proteins (page 115, right column, paragraph 1).
Li describes that regulation of plant NLRs at the levels of transcription, RNA processing, protein folding, and degradation is important, because over-accumulation can lead to autoimmunity or dwarf phenotypes and insufficiency can lead to susceptibility (page 115, right column, paragraph 4). Li describes that alternative splicing can be a crucial step in the regulation of NLR gene expression (page 117, left column, paragraph 2).
Li also describes that downstream signaling activation is a key step for the activation of immune response, and several signaling proteins have been shown to interact with NLRs although the mechanisms of how signaling components are activated is unknown (page 117, right column, paragraph 5-page 188, left column, paragraph 1).
Li describes common domains found in plant NLRs but describes that truncated NLRs and NLRs with atypical domains are also known (figure 1). Baggs et al (2017) Current Opinion in Plant Biology. 38:59–67 (published 5/8/2017, hereafter Baggs) describes NLRs as comprising NB-ARC domains in combination with the second greatest diversity of other domains than any other protein module (page 64, left column, paragraph 3). Triticum aestivum, in particular, is a plant with an extreme expansion of NLRs normalized against total number of proteins (Baggs figure 1). Individual NLR genes can be associated with allelic diversity due to point mutations, recombination, or domain fusions, illustrating selection pressures. These polymorphisms can determine specificity to pathogen effectors (Baggs, page 61, left column, paragraph 1).
Thus, NLR proteins conferring disease resistance comprise great diversity, including within species, and the diversity of NLR proteins and their regulation affects resistance and specificity of resistance to diseases.
Beyond introns of the genomic sequence, which Applicant has described as important for the resistance phenotype, Applicant has not described which features of the encompassed nucleotides encoding polypeptide sequences are responsible for conferring resistance to rust diseases specifically.
The structural features that distinguish polypeptides with 80% identity to SEQ ID NO: 1 which confer tolerance to rust disease from other polypeptides with 80% identity to SEQ ID NO: 1 are not described in the specification. Given the high diversity of the proteins conferring tolerance to disease, one of skill in the art would not recognize that Applicant was in possession of the necessary common attributes or features of the genus in view of the disclosed species.
Hence, Applicant has not, in fact, described polynucleotides that encode a polypeptide with 80% identity to SEQ ID NO: 1 and confer tolerance to a rust disease 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.
Scope of Enablement
Claims 1, 3, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 43, & 45-47 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 polynucleotide encoding a polypeptide of SEQ ID NO: 1 capable of conferring or enhancing tolerance and/or resistance of a Triticeae plant to at least one rust disease, does not reasonably provide enablement for any polynucleotide encoding a polypeptide having at least 80% identity to SEQ ID NO: 1 that is capable of conferring or enhancing tolerance to a rust disease. 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, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 43, & 45-47 all require a plant comprising a polynucleotide encoding a polypeptide having at least 80% identity to SEQ ID NO: 1 capable of conferring or enhancing tolerance and/or resistance of a Triticeae plant to at least one rust disease.
Polypeptides with 80% identity to SEQ ID NO: 1 encompass amino acid sequences with 302 substitutions relative to the 1510 amino acid-long SEQ ID NO: 1. Polynucleotides with 70% identity to the 16207-nucleotide long SEQ ID NO: 6 would have 4862 nucleotide substitutions relative to SEQ ID NO: 6, and polynucleotides with 88% identity to the 4533 nucleotide-long SEQ ID NO: 3 would have 543 substitutions relative to SEQ ID NO: 3. Because these nucleic acids encompass those in which substitution occurs across different codons and in which every substitution results in codon that encodes a different amino acid, the recited polynucleotide sequences do not narrow the breadth of encoded amino acid sequences encompassed by the instant invention.
While the claims are drawn to polynucleotides capable of conferring tolerance to a rust disease and encoding a polypeptide with 80% identity to SEQ ID NO: 1, the specification teaches only one polypeptide with at least 80% identity to SEQ ID NO: 1: SEQ ID NO: 1. See tables 5 & 6 of the specification. The specification teaches two sequences encoding SEQ ID NO: 1, SEQ ID NOs: 3 & 6, and no polynucleotides encoding sequences with as little as 80% identity to SEQ ID NO: 1. The specification additionally provides SEQ ID NO: 68, which comprises both the coding sequence and an endogenous promoter and terminator. Thus, the specification does not teach examples of species over the full scope of the polypeptides, and thus does not enable one of ordinary skill in the art to make the full scope of the claimed nucleic acids.
The specification teaches that the Lr/Yr5458 gene, which encodes SEQ ID NO: 1, belongs to the family of NLR disease resistance genes (page 21, lines 3-9) and confers resistance to two different wheat pathogens (page 32, lines 4-13). The specification teaches that tolerance from Lr/Yr5458 does not lead to a hyper-sensitive response but slows down pathogen development and disease progression and is stable across ages, so it is not an adult plant resistance gene (page 32, line 14-25). The specification does not teach a mechanism of the resistance against two different pathogen species but proposes that Lr/Yr548 could possibly recognize two alternative effectors or that the rust diseases contain a common effector (page 32, line 26-page 33, line 3). The specification teaches domains within the resistance conferring gene, including Rx_N domain, NB-ARC domain, and LRR domains (table 3) but does not teach the features specifically responsible for the recognition and tolerance to rust diseases.
The specification teaches that the Lr/Yr548 gene's closest homolog is an uncharacterized RGA2 gene with 87% identity from Ae. tauschii, but that this homolog is not a functional homolog of Lr/Yr548 (page 33, lines 4-12). The specification also teaches an RGA2-like putative disease resistance gene from Triticum urartu with 83% identity to SEQ ID NO: 3, but all other predicted genes had less than 80% homology or 80% coverage (page 46, line 4-13; tables 5, 6). The specification teaches an Ae. sharonensis resistance gene similar to Lr/Yr548 that has only minor sequence homology and that the CC domain differs from common CC domains (page 49, line 10-page 50, line 9). The instant specification suggests that there is no functional homologue of the Lr/Yr548 gene in current databases (page 49, lines 8-9).
The specification teaches constructs for transformation comprising artificially shortened exons or comprising cDNA (page 38, line 14-page 39, line 1). Both constructs were introduced into wheat (page 44, line 5-page 45, line 6) and only the gDNA transgene lines had resistance (figure 9). This example teaches the introns to be important for proper gene expression (page 45, lines 4-6), although features of the introns responsible for proper gene expression are not taught.
A polynucleotide encoding a polypeptide of instant SEQ ID NO: 1 is known in the art. US 20240218356A1 (published post filing, but with an effective filing date of 5/11/2021) teaches a nucleic acid with 99% similarity to instant SEQ ID NO: 3 encoding a protein with 100% similarity to instant SEQ ID NO: 1. See alignments above.
Other than this identical protein, the polypeptides taught by the prior art are less than 80% similar to instant SEQ ID NO: 1. UniProt record A0ACD5WJ07_AVESA (available 1/28/2026) teaches an uncharacterized protein in oat with 68.7% sequence identity to instant SEQ ID NO: 1. See alignment above.
The prior art teaches that NLR resistance genes generally follow a gene-for-gene pattern with a specific effector for recognition, and that while plant NLRs can recognize effectors directly through protein-protein interaction, most often they interact with host proteins (Li et al (2015) Current Opinion in Immunology. 32:114–121 (published 2/6/2015, hereafter Li) page 115, right column, paragraph 1). Li teaches that downstream signaling activation is a key step for the activation of immune response, and several signaling proteins have been shown to interact with NLR, although the mechanisms of how signaling components are activated is unknown (page 117, right column, paragraph 5-page 188, left column, paragraph 1).
Li teaches that regulation of plant NLRs at the levels of transcription, RNA processing, protein folding, and degradation is important, because over-accumulation can lead to autoimmunity or dwarf phenotypes and insufficiency can lead to susceptibility (page 115, right column, paragraph 4). Li teaches that alternative splicing can be a crucial step in the regulation of NLR gene expression (page 117, left column, paragraph 2).
Li teaches common domains found in plant NLRs but truncated NLRs and NLRs with atypical domains are also known (figure 1). Baggs et al (2017) Current Opinion in Plant Biology. 38:59–67 (published 5/8/2017, hereafter Baggs) teaches that NLRs comprise NB-ARC domains in combination with the second greatest diversity of other domains than any other protein module (page 64, left column, paragraph 3). The NLR protein family in plants often comprises hundreds of members (Li page 114, left column, paragraph 1-right column, paragraph 1), and Triticum aestivum, in particular, is a plant with an extreme expansion of NLRs normalized against total number of proteins (Baggs figure 1). Individual NLR genes can be have allelic diversity due to point mutations, recombination, or domain fusions, illustrating selection pressures. These polymorphisms can determine specificity to pathogen effectors (Baggs, page 61, left column, paragraph 1).
Thus, one of skill in the art would know from the art that NLR proteins conferring disease resistance are highly diverse, these proteins interact with both host and sometimes directly with pathogen proteins, and the diversity of these proteins and their regulation affects resistance and specificity of resistance to diseases.
Beyond introns of the genomic sequence, which Applicant teaches to be important for the resistance phenotype, Applicant has not taught any structural features of the encompassed nucleotides encoding polypeptide sequences that are responsible for conferring resistance to rust diseases specifically. Because Applicant does not teach structural features that distinguish polypeptides with 80% identity to SEQ ID NO: 1 which confer tolerance to rust disease from other polypeptides with 80% identity to SEQ ID NO: 1, one of ordinary skill in the art would be required to conduct undue trial and error experimentation over a large number of encompassed polynucleotides, in a large number of encompassed Triticeae plants, in response to multiple rust disease pathogens, to determine which sequences, in which plants, confer resistance or tolerance to a rust disease, if any.
Hence, the instant disclosure, while enabling for a polynucleotide encoding instant SEQ ID NO: 1 in wheat which confers resistance to rust disease is not enabled over the full scope of the genus of claimed polynucleotides encoding polypeptides with as little as 80% identity to SEQ ID NO: 1 across all Triticeae plants and rust diseases.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 46, 47 & 61 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Moscou et al US 2024/0218356 A1 (published 7/4/2024 with a priority date of 5/11/2021 and a PCT filing date of 5/11/2022, both of which pre-date the effective filing date of the instant application; hereafter Moscou).
Moscou discloses a nucleic acid sequence (Moscou SEQ ID NO: 25) with 99% sequence identity to instant SEQ ID NO: 3 (first alignment below) which encodes a protein with 100% sequence identity to instant SEQ ID NO: 1 (second alignment below). This sequence is labeled Dk_01_19 and is the coding region of an NLR from Aegilops sharonensis (paragraph [0055]). Moscou discloses cloning NLR sequences from Aegilops into a Gateway pDONR entry vector and transferred to a pDEST2BL binary vector and used to transform a wheat variety (paragraphs [0351-0353]). Moscou discloses that wheat plants transformed with Dk_01_19 exhibited resistance to wheat leaf rust (Puccinia triticina) (paragraphs [0361-0362], table 4). Moscou discloses a method for assaying the NLR genes by inoculating three seeds from four different families of NLRs, saving seed from families with resistant seedling phenotypes, and re-phenotyping eight seeds grown at the T2 stage (paragraphs [0354-0355]). For leaf rust, plants were inoculated at first leaf stage scored for resistance phenotype on a standard phenotypic scale (paragraph [0361]).
US-18-558-574-25
Sequence 25, US/18558574
Publication No. US20240218356A1
GENERAL INFORMATION
APPLICANT: Two Blades Foundation
APPLICANT: Moscou, Matthew J
APPLICANT: van Esse, Hendrikus P
TITLE OF INVENTION: METHODS FOR PREPARING A LIBRARY OF PLANT DISEASE RESISTANCE GENES
TITLE OF INVENTION: FOR FUNCTIONAL TESTING FOR DISEASE RESISTANCE
FILE REFERENCE: 070294.0225
CURRENT APPLICATION NUMBER: US/18/558,574
CURRENT FILING DATE: 2023-11-02
PRIOR APPLICATION NUMBER: PCT/US2022/028686
PRIOR FILING DATE: 2022-05-11
PRIOR APPLICATION NUMBER: US 63/186,986
PRIOR FILING DATE: 2021-05-11
NUMBER OF SEQ ID NOS: 188
SEQ ID NO 25
LENGTH: 4530
TYPE: DNA
ORGANISM: Aegilops sharonensis
FEATURE:
NAME/KEY: CDS
LOCATION: (1)..(4530)
Query Match 99.8%; Score 4525.2; Length 4530;
Best Local Similarity 99.9%;
Matches 4527; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 1 ATGAGCGGGGTTGGGGAGATGATCGCGAGTGCCGTGGTGAAGCAAATCACTAGCAGGCTA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGAGCGGGGTTGGGGAGATGATCGCGAGTGCCGTGGTGAAGCAAATCACTAGCAGGCTA 60
Qy 61 ATCAAACTCCTCGAAGATGAGACCACTATGCAGTGGAAGTTTAAAGGCGAGGTGGATAAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ATCAAACTCCTCGAAGATGAGACCACTATGCAGTGGAAGTTTAAAGGCGAGGTGGATAAA 120
Qy 121 ATGGCAGAGAAAATGAAATATCTGGCAGCTGTGATGCATGATGCTGATGATAAAGTGCGC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ATGGCAGAGAAAATGAAATATCTGGCAGCTGTGATGCATGATGCTGATGATAAAGTGCGC 180
Qy 181 CGAGGAGGAAGGGTTGGAGAAACAGTTGGGCTATGGCTCCTGAAATTGAAATCCATCTCC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CGAGGAGGAAGGGTTGGAGAAACAGTTGGGCTATGGCTCCTGAAATTGAAATCCATCTCC 240
Qy 241 CACGACGTTGAGGACCTGCTGGACGACTTGGACACTAAGAATAACGAAGCAAAGCTCAAG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CACGACGTTGAGGACCTGCTGGACGACTTGGACACTAAGAATAACGAAGCAAAGCTCAAG 300
Qy 301 GTATTCTTTTCGGGGAACAATCAAGCTTACCGGTGGATAACTAGGCCCCATCGTTTGAAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GTATTCTTTTCGGGGAACAATCAAGCTTACCGGTGGATAACTAGGCCCCATCGTTTGAAG 360
Qy 361 GACGTGGGGAAGAGAATAGAAGAAATAAAAAAGGAGGGCTGCGAGTTCAATCTGGATCCT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GACGTGGGGAAGAGAATAGAAGAAATAAAAAAGGAGGGCTGCGAGTTCAATCTGGATCCT 420
Qy 421 AAAGCACAAGTCGAACAAAGACAAGAAGAGACTTATGCAACCATCAGCGCGACAACTGGA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 AAAGCACAAGTCGAACAAAGACAAGAAGAGACTTATGCAACCATCAGCGCGACAACTGGA 480
Qy 481 ATGCAAGGGAGGAGCGCTGAAAAAGAAAAATTAATAAATTTGATATTGCGAAGCCAAGCT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 ATGCAAGGGAGGAGCGCTGAAAAAGAAAAATTAATAAATTTGATATTGCGAAGCCAAGCT 540
Qy 541 AATGAGCGTATCTCCATAATTCCAATTGTTGGCCTTGGTGGTATAGGGAAGACAACATTG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 AATGAGCGTATCTCCATAATTCCAATTGTTGGCCTTGGTGGTATAGGGAAGACAACATTG 600
Qy 601 GCTCGGTCAGTTTGGGCAGATGAGAAATTCAACATCTTCGACATCAAAGCCTGGGTTCAT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GCTCGGTCAGTTTGGGCAGATGAGAAATTCAACATCTTCGACATCAAAGCCTGGGTTCAT 660
Qy 661 GTGTCTGACAAGTTTGATTTGCATAAAATTGCGAGAACCATCATCAGAAGCGTAGATACC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GTGTCTGACAAGTTTGATTTGCATAAAATTGCGAGAACCATCATCAGAAGCGTAGATACC 720
Qy 721 GATATCAATCTTGATAGCAATGATTTGCATTTTCTGCAGAATATTCTTCGAGTCAAACTT 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GATATCAATCTTGATAGCAATGATTTGCATTTTCTGCAGAATATTCTTCGAGTCAAACTT 780
Qy 781 GCTGGTAAAAAGTACTTGATTTTTTTGGATGATATCTGGGAAGAAGATGGAGATAAGCTG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GCTGGTAAAAAGTACTTGATTTTTTTGGATGATATCTGGGAAGAAGATGGAGATAAGCTG 840
Qy 841 GACAAGCTGAAGGACATGCTACAGCATGGCTCCAACGGTAGCAGGATTATAATTACTACA 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 GACAAGCTGAAGGACATGCTACAGCATGGCTCCAACGGTAGCAGGATTATAATTACTACA 900
Qy 901 CGTAACCAAAGGATAGTGGAAACAATGAGCACCGGCATTCTTGCACATGAGAGGGTAATT 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 CGTAACCAAAGGATAGTGGAAACAATGAGCACCGGCATTCTTGCACATGAGAGGGTAATT 960
Qy 961 CTCCCGGTGCATGAGTCTGACAGAATCAAATTGGGTGTTCTGCCAACCGATGACTGCTGG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 CTCCCGGTGCATGAGTCTGACAGAATCAAATTGGGTGTTCTGCCAACCGATGACTGCTGG 1020
Qy 1021 GAATTAATGAAGATAAGGGCATTTGGTCCTGATGATGACCAGACTCCTTTGAAACAAATC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GAATTAATGAAGATAAGGGCATTTGGTCCTGATGATGACCAGACTCCTTTGAAACAAATC 1080
Qy 1081 GGGTATGAAATTGCAAGTAAATGTGGGGGTATACCACTCGTGGCAAATGCTTTCGGGAAA 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 GGGTATGAAATTGCAAGTAAATGTGGGGGTATACCACTCGTGGCAAATGCTTTCGGGAAA 1140
Qy 1141 GTAATGTCAGGGAATAAGTCCATCGCAGCATGGCAGTATATAAAAGATAGGATGGTTGAT 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 GTAATGTCAGGGAATAAGTCCATCGCAGCATGGCAGTATATAAAAGATAGGATGGTTGAT 1200
Qy 1201 TTGGGTTTGAGAGACGAAGATCAAAAAGACACATTAGAGTCTCTCAAGTTGAGTTATTAC 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 TTGGGTTTGAGAGACGAAGATCAAAAAGACACATTAGAGTCTCTCAAGTTGAGTTATTAC 1260
Qy 1261 TTCATGAAGCTGGAGTTCAAAATTTGTTTCTCGTATTTGGCGGCATTTCCCAAGGGCTTC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 TTCATGAAGCTGGAGTTCAAAATTTGTTTCTCGTATTTGGCGGCATTTCCCAAGGGCTTC 1320
Qy 1321 ATTATAGACACCAACCGTTTAATCCAGCAATGGAATGCACTTGGATACATTTATTCAGAA 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 ATTATAGACACCAACCGTTTAATCCAGCAATGGAATGCACTTGGATACATTTATTCAGAA 1380
Qy 1381 CATGATGGTAAAAACTGCATCGACTACCTTCTTGGGATGTCCTTTCTTCAGATTTCAGGA 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 CATGATGGTAAAAACTGCATCGACTACCTTCTTGGGATGTCCTTTCTTCAGATTTCAGGA 1440
Qy 1441 CCTTCTTCGGCTAGTCAAAGTCCAGCGTGTGCCAATGCATCTGGGGAGCTTACCATGCAT 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 CCTTCTTCGGCTAGTCAAAGTCCAGCGTGTGCCAATGCATCTGGGGAGCTTACCATGCAT 1500
Qy 1501 GATCTGGTACATGATCTTGCGTTAGTAATTACTGTTGATGAATTCCTTGTTTTGGATGCT 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 GATCTGGTACATGATCTTGCGTTAGTAATTACTGTTGATGAATTCCTTGTTTTGGATGCT 1560
Qy 1561 GATGCTACTGGACCAAGGACTTGGAAAAAAGCTATTCACTGCCGACATGCAGAGTTGATA 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 GATGCTACTGGACCAAGGACTTGGAAAAAAGCTATTCACTGCCGACATGCAGAGTTGATA 1620
Qy 1621 CAATACAAGAATCAATCCAATGTTTTCGAGCATCTGCCAAAAAAGCTTAGATCCCTCCAT 1680
|||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||
Db 1621 CAATACAAGAATCAATCCAATGTTTTCGAGCATCTGCCGAAAAAGCTTAGATCCCTCCAT 1680
Qy 1681 ATTAGAGATTCACTGAAATGGAAACTCCCTCCAAAGGCCTTTTCTCGATGCAAGTACATG 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 ATTAGAGATTCACTGAAATGGAAACTCCCTCCAAAGGCCTTTTCTCGATGCAAGTACATG 1740
Qy 1741 CGTGTCTTGGACCTAGCATGTTTAGTAGGGCAACTCTCTGAAGGGCAATCAACGTCAAGC 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 CGTGTCTTGGACCTAGCATGTTTAGTAGGGCAACTCTCTGAAGGGCAATCAACGTCAAGC 1800
Qy 1801 AACATGAGGCTGCCACGTTCCATAAACAAAATGAAGCTACTTAGGTACCTTGATGCCACG 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 AACATGAGGCTGCCACGTTCCATAAACAAAATGAAGCTACTTAGGTACCTTGATGCCACG 1860
Qy 1861 GGATTGCCAGTTTCTTCACTTTCTAAGTCTTTGCATATACTTCAAAATATGGAAACTCTG 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1861 GGATTGCCAGTTTCTTCACTTTCTAAGTCTTTGCATATACTTCAAAATATGGAAACTCTG 1920
Qy 1921 ATAATGTCCAATTGCTCACTTGAAACCTTGCCTGACAATGTTTGTAGCCTCCACAAACTT 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1921 ATAATGTCCAATTGCTCACTTGAAACCTTGCCTGACAATGTTTGTAGCCTCCACAAACTT 1980
Qy 1981 AGCTATCTTGATCTGTCCGGTAATAGAAGCCTTAATAAGCTACCTACGTCGTTGGGCAAG 2040
|||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||
Db 1981 AGCTATCTTGATCTGTCCGGTAATAGAAGCCTTAATAAGCTACCTACGTCGTTGGGTAAG 2040
Qy 2041 CTCTCTAAGCTCTCTTTCCTCAACTTATCAGGGTGTTCCGTCCTCCAAGGGGTGCCTAAA 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2041 CTCTCTAAGCTCTCTTTCCTCAACTTATCAGGGTGTTCCGTCCTCCAAGGGGTGCCTAAA 2100
Qy 2101 TCCATTTGCCAGTTGACATGTTTACAATACCTAGACATGTCAGAGTGTCGTGCCGTTCAA 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2101 TCCATTTGCCAGTTGACATGTTTACAATACCTAGACATGTCAGAGTGTCGTGCCGTTCAA 2160
Qy 2161 AATCTTCCTGATAAGTTTGGTAGCCTACCAAATATCTCATTCCTAAATTTGTCCGGTTGC 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2161 AATCTTCCTGATAAGTTTGGTAGCCTACCAAATATCTCATTCCTAAATTTGTCCGGTTGC 2220
Qy 2221 TCAAAATTAACCAAACTACCTGACATTGTTAACCTTGAGTCTTTGGAGCATTTCGACCTA 2280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2221 TCAAAATTAACCAAACTACCTGACATTGTTAACCTTGAGTCTTTGGAGCATTTCGACCTA 2280
Qy 2281 TCAAGTTGCCACGAGCTAAAAGACCTCCCACAAGATTTTGGTAATCTTCAAAATCTTGTG 2340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2281 TCAAGTTGCCACGAGCTAAAAGACCTCCCACAAGATTTTGGTAATCTTCAAAATCTTGTG 2340
Qy 2341 TTCTTGAGCCTCTCTGATTGCTACAAGGTTTCAGTGCTCCCGGAATCATTTTGCCAGCTT 2400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2341 TTCTTGAGCCTCTCTGATTGCTACAAGGTTTCAGTGCTCCCGGAATCATTTTGCCAGCTT 2400
Qy 2401 ATTCATTTGAAATACCTAGATCTTTCAGATTGCCATGGCCTCAGGGAACTCCCAGAGTGT 2460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2401 ATTCATTTGAAATACCTAGATCTTTCAGATTGCCATGGCCTCAGGGAACTCCCAGAGTGT 2460
Qy 2461 TTTGGTAACCTTTCTGAGCTTGACTCATTGAACCTAATAAGTTGTTCCAAGCTGCAAGTA 2520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2461 TTTGGTAACCTTTCTGAGCTTGACTCATTGAACCTAATAAGTTGTTCCAAGCTGCAAGTA 2520
Qy 2521 CTGCCTGACTCATTCTGTAGCTTGTTTAAGCTGAGGCATCTCAATTTGTCATACTGTATG 2580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2521 CTGCCTGACTCATTCTGTAGCTTGTTTAAGCTGAGGCATCTCAATTTGTCATACTGTATG 2580
Qy 2581 AGGCTTGAAAAGCTCCCATCCTCGTTAGGTGACCTTAAGCTTCGGTTATTGGACATCTCT 2640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2581 AGGCTTGAAAAGCTCCCATCCTCGTTAGGTGACCTTAAGCTTCGGTTATTGGACATCTCT 2640
Qy 2641 GCTGCAACTTTCCATGATTTACCGGATAGCATCCGTGGCATGACTACACTCACTAAACTT 2700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2641 GCTGCAACTTTCCATGATTTACCGGATAGCATCCGTGGCATGACTACACTCACTAAACTT 2700
Qy 2701 GTGGTCTCGACAGCACAACTAGGGGTTCATAACAAGGTTCGTGACATTCGGCAGCATCTG 2760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2701 GTGGTCTCGACAGCACAACTAGGGGTTCATAACAAGGTTCGTGACATTCGGCAGCATCTG 2760
Qy 2761 AATTTGCCAGGGGAGATAGTACATACTGTACATCTGACTGAAAACAAAGGATGTAGCAGT 2820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2761 AATTTGCCAGGGGAGATAGTACATACTGTACATCTGACTGAAAACAAAGGATGTAGCAGT 2820
Qy 2821 ATTGTAGAGTTAGCACAATTGACCTGTCAAAACTTGAAAGTCTTACAACTTCAGAATGTC 2880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2821 ATTGTAGAGTTAGCACAATTGACCTGTCAAAACTTGAAAGTCTTACAACTTCAGAATGTC 2880
Qy 2881 AGGCATCCGGAAGATGCAGAGAGAGCCAAGTTACGTGATAAATCAGATCTTCGGGTTCTA 2940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2881 AGGCATCCGGAAGATGCAGAGAGAGCCAAGTTACGTGATAAATCAGATCTTCGGGTTCTA 2940
Qy 2941 TGGCTTTGTTGGGGACTCCAGCGAGAAGAGGATATTTATGTGCTGGAGAGGCTTGTACCT 3000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2941 TGGCTTTGTTGGGGACTCCAGCGAGAAGAGGATATTTATGTGCTGGAGAGGCTTGTACCT 3000
Qy 3001 CCACGCAATCTTGAACATTTTACGCTAGATGGGTATATGAGCAAGGATTTCCCTAACTGG 3060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3001 CCACGCAATCTTGAACATTTTACGCTAGATGGGTATATGAGCAAGGATTTCCCTAACTGG 3060
Qy 3061 ATTTCTCACATCTCCACATACCTTCCTTATCTCACCTTTCTCACCCTTTGCAATTTAGGA 3120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3061 ATTTCTCACATCTCCACATACCTTCCTTATCTCACCTTTCTCACCCTTTGCAATTTAGGA 3120
Qy 3121 GCATGTGATAATCTTCCACCATTTGGGCAACTGCCAAATTTAAGATGTCTAGAGATGAAT 3180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3121 GCATGTGATAATCTTCCACCATTTGGGCAACTGCCAAATTTAAGATGTCTAGAGATGAAT 3180
Qy 3181 TATATTCCTAACATCACAAAAATTGGCAAGGAATTCTATGGAGAAGGTGGAACCTGTAGG 3240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3181 TATATTCCTAACATCACAAAAATTGGCAAGGAATTCTATGGAGAAGGTGGAACCTGTAGG 3240
Qy 3241 AAATTAAGAAGTATACAATTGAAGTCAATGGAGAATTTGGTGGAATGGTGGACTGCACTC 3300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3241 AAATTAAGAAGTATACAATTGAAGTCAATGGAGAATTTGGTGGAATGGTGGACTGCACTC 3300
Qy 3301 TCAGGTGAGAAAAATGAAGAGTCACTGATCCCTAATTTGCATTGTTTGTCAATAAGGAAC 3360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3301 TCAGGTGAGAAAAATGAAGAGTCACTGATCCCTAATTTGCATTGTTTGTCAATAAGGAAC 3360
Qy 3361 TGCCCCAAGTTGAAGTTCCTACCATATCCCCCGAGGAGTATGTTTTGGCACTTGGATAAT 3420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3361 TGCCCCAAGTTGAAGTTCCTACCATATCCCCCGAGGAGTATGTTTTGGCACTTGGATAAT 3420
Qy 3421 AGCAGCATGGTTTCGCCAAAAGAGGGATTTGGAAAGCTTTCTTCTTACGCTTTTCCTTTT 3480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3421 AGCAGCATGGTTTCGCCAAAAGAGGGATTTGGAAAGCTTTCTTCTTACGCTTTTCCTTTT 3480
Qy 3481 CTCATGGTAGTAAGAAACTGCAACTTTGCTCCAGACAAATGGGATTGGCTTCAACACCTC 3540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3481 CTCATGGTAGTAAGAAACTGCAACTTTGCTCCAGACAAATGGGATTGGCTTCAACACCTC 3540
Qy 3541 CCCACCCTTGAGATATTTTATGTTGAGAGCATCAATGGCTTGAGGGCATTGCCAGAGGCC 3600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3541 CCCACCCTTGAGATATTTTATGTTGAGAGCATCAATGGCTTGAGGGCATTGCCAGAGGCC 3600
Qy 3601 ATGCAATGTTTAAACTCTCTCACAAGACTAAATTTGTGGTCATTAAAGGACCTGGAGAAA 3660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3601 ATGCAATGTTTAAACTCTCTCACAAGACTAAATTTGTGGTCATTAAAGGACCTGGAGAAA 3660
Qy 3661 CTGCCAGAATGGTTGGGGGACCTCACTTCTCTAGAATACATTCACATCAAAGATTGTCCC 3720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3661 CTGCCAGAATGGTTGGGGGACCTCACTTCTCTAGAATACATTCACATCAAAGATTGTCCC 3720
Qy 3721 ATGGTGACATCTTTGCCTGTAAGAATGAAGTGTCTTGCTGCTCTTAGAGAACTTTGCCTG 3780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3721 ATGGTGACATCTTTGCCTGTAAGAATGAAGTGTCTTGCTGCTCTTAGAGAACTTTGCCTG 3780
Qy 3781 GCGGAGTGCAGAGGCCTAGAAGTATTGCCAGAATGGCTGGGACATCTGACTTCCCTACAA 3840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3781 GCGGAGTGCAGAGGCCTAGAAGTATTGCCAGAATGGCTGGGACATCTGACTTCCCTACAA 3840
Qy 3841 GAGTTCTATATCATGAGTTGCCCCAACCTGACTTCTTTGCCTGAAAGCATGAAGTGTCTT 3900
||||||||||||||||||||||||||||||||||| ||||||||||||||||||||||||
Db 3841 GAGTTCTATATCATGAGTTGCCCCAACCTGACTTCCTTGCCTGAAAGCATGAAGTGTCTT 3900
Qy 3901 ACTGCTCTCAGAGTACTTCGGCTGATGGAGTGCGAAGGCCTAGAAGTATTGCCAGAATGG 3960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3901 ACTGCTCTCAGAGTACTTCGGCTGATGGAGTGCGAAGGCCTAGAAGTATTGCCAGAATGG 3960
Qy 3961 CTGGGACATCTCACTTCCCTACAAGAGTTCTATATCATCCGTTGCCCCAACCTGACTTCT 4020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3961 CTGGGACATCTCACTTCCCTACAAGAGTTCTATATCATCCGTTGCCCCAACCTGACTTCT 4020
Qy 4021 TTGCCTAAAAGCATGAAGTGTCTTACTGCTCTCAGAGTACTTTGGCTGACGGAGTGCGAA 4080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4021 TTGCCTAAAAGCATGAAGTGTCTTACTGCTCTCAGAGTACTTTGGCTGACGGAGTGCGAA 4080
Qy 4081 GGCCTAGAAGTATTCCCAGAATGGCTAGGACATCTCATTTCCCTACAAGAGTTTTACATC 4140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4081 GGCCTAGAAGTATTCCCAGAATGGCTAGGACATCTCATTTCCCTACAAGAGTTTTACATC 4140
Qy 4141 ACCTGTTGCTCCAACCTGACTTGTTTGCCTGTAAGCATGAAGCGTCTTACTGCTCTGAGA 4200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4141 ACCTGTTGCTCCAACCTGACTTGTTTGCCTGTAAGCATGAAGCGTCTTACTGCTCTGAGA 4200
Qy 4201 TTACTCTGGTTGGGCCAGTGTGAAGGTCTAGACGTATTGCCAGAATGGTTGGGACAGCTC 4260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4201 TTACTCTGGTTGGGCCAGTGTGAAGGTCTAGACGTATTGCCAGAATGGTTGGGACAGCTC 4260
Qy 4261 ATCTCCCTTCAAGAATTTAACATCGTCGGTTGCCCGAACTTGACACATTTTCCTGAAAGC 4320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4261 ATCTCCCTTCAAGAATTTAACATCGTCGGTTGCCCGAACTTGACACATTTTCCTGAAAGC 4320
Qy 4321 ACACGGAACCTTACCGCCTTGAAGAAACTGAATATTTGGGGATGTCCGAGTCTTGTTGAG 4380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4321 ACACGGAACCTTACCGCCTTGAAGAAACTGAATATTTGGGGATGTCCGAGTCTTGTTGAG 4380
Qy 4381 AGGTGCCAAGGGGAGGATGCTGACCTGATTTCTCATATCCCGGAAGTCTTGTTAGAAGGA 4440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4381 AGGTGCCAAGGGGAGGATGCTGACCTGATTTCTCATATCCCGGAAGTCTTGTTAGAAGGA 4440
Qy 4441 AAAACTAGAGAATTGTGGTCGACTTCCGGAGATGCTGAAGCATCGACTTCCGGAGCATCG 4500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4441 AAAACTAGAGAATTGTGGTCGACTTCCGGAGATGCTGAAGCATCGACTTCCGGAGCATCG 4500
Qy 4501 ACTGCTGAAGAAGCTGGACCATCGACTTCT 4530
||||||||||||||||||||||||||||||
Db 4501 ACTGCTGAAGAAGCTGGACCATCGACTTCT 4530
Length: 4530
Score: 7946.00 Matches: 1510
Percent Similarity: 100.0% Conservative: 0
Best Local Similarity: 100.0% Mismatches: 0
Query Match: 100.0% Indels: 0
Gaps: 0
US-18-876-444-1 (1-1510) x US-18-558-574-25 (1-4530)
Qy 1 MetSerGlyValGlyGluMetIleAlaSerAlaValValLysGlnIleThrSerArgLeu 20
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGAGCGGGGTTGGGGAGATGATCGCGAGTGCCGTGGTGAAGCAAATCACTAGCAGGCTA 60
Qy 21 IleLysLeuLeuGluAspGluThrThrMetGlnTrpLysPheLysGlyGluValAspLys 40
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ATCAAACTCCTCGAAGATGAGACCACTATGCAGTGGAAGTTTAAAGGCGAGGTGGATAAA 120
Qy 41 MetAlaGluLysMetLysTyrLeuAlaAlaValMetHisAspAlaAspAspLysValArg 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ATGGCAGAGAAAATGAAATATCTGGCAGCTGTGATGCATGATGCTGATGATAAAGTGCGC 180
Qy 61 ArgGlyGlyArgValGlyGluThrValGlyLeuTrpLeuLeuLysLeuLysSerIleSer 80
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CGAGGAGGAAGGGTTGGAGAAACAGTTGGGCTATGGCTCCTGAAATTGAAATCCATCTCC 240
Qy 81 HisAspValGluAspLeuLeuAspAspLeuAspThrLysAsnAsnGluAlaLysLeuLys 100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CACGACGTTGAGGACCTGCTGGACGACTTGGACACTAAGAATAACGAAGCAAAGCTCAAG 300
Qy 101 ValPhePheSerGlyAsnAsnGlnAlaTyrArgTrpIleThrArgProHisArgLeuLys 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GTATTCTTTTCGGGGAACAATCAAGCTTACCGGTGGATAACTAGGCCCCATCGTTTGAAG 360
Qy 121 AspValGlyLysArgIleGluGluIleLysLysGluGlyCysGluPheAsnLeuAspPro 140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GACGTGGGGAAGAGAATAGAAGAAATAAAAAAGGAGGGCTGCGAGTTCAATCTGGATCCT 420
Qy 141 LysAlaGlnValGluGlnArgGlnGluGluThrTyrAlaThrIleSerAlaThrThrGly 160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 AAAGCACAAGTCGAACAAAGACAAGAAGAGACTTATGCAACCATCAGCGCGACAACTGGA 480
Qy 161 MetGlnGlyArgSerAlaGluLysGluLysLeuIleAsnLeuIleLeuArgSerGlnAla 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 ATGCAAGGGAGGAGCGCTGAAAAAGAAAAATTAATAAATTTGATATTGCGAAGCCAAGCT 540
Qy 181 AsnGluArgIleSerIleIleProIleValGlyLeuGlyGlyIleGlyLysThrThrLeu 200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 AATGAGCGTATCTCCATAATTCCAATTGTTGGCCTTGGTGGTATAGGGAAGACAACATTG 600
Qy 201 AlaArgSerValTrpAlaAspGluLysPheAsnIlePheAspIleLysAlaTrpValHis 220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GCTCGGTCAGTTTGGGCAGATGAGAAATTCAACATCTTCGACATCAAAGCCTGGGTTCAT 660
Qy 221 ValSerAspLysPheAspLeuHisLysIleAlaArgThrIleIleArgSerValAspThr 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GTGTCTGACAAGTTTGATTTGCATAAAATTGCGAGAACCATCATCAGAAGCGTAGATACC 720
Qy 241 AspIleAsnLeuAspSerAsnAspLeuHisPheLeuGlnAsnIleLeuArgValLysLeu 260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GATATCAATCTTGATAGCAATGATTTGCATTTTCTGCAGAATATTCTTCGAGTCAAACTT 780
Qy 261 AlaGlyLysLysTyrLeuIlePheLeuAspAspIleTrpGluGluAspGlyAspLysLeu 280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GCTGGTAAAAAGTACTTGATTTTTTTGGATGATATCTGGGAAGAAGATGGAGATAAGCTG 840
Qy 281 AspLysLeuLysAspMetLeuGlnHisGlySerAsnGlySerArgIleIleIleThrThr 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 GACAAGCTGAAGGACATGCTACAGCATGGCTCCAACGGTAGCAGGATTATAATTACTACA 900
Qy 301 ArgAsnGlnArgIleValGluThrMetSerThrGlyIleLeuAlaHisGluArgValIle 320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 CGTAACCAAAGGATAGTGGAAACAATGAGCACCGGCATTCTTGCACATGAGAGGGTAATT 960
Qy 321 LeuProValHisGluSerAspArgIleLysLeuGlyValLeuProThrAspAspCysTrp 340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 CTCCCGGTGCATGAGTCTGACAGAATCAAATTGGGTGTTCTGCCAACCGATGACTGCTGG 1020
Qy 341 GluLeuMetLysIleArgAlaPheGlyProAspAspAspGlnThrProLeuLysGlnIle 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GAATTAATGAAGATAAGGGCATTTGGTCCTGATGATGACCAGACTCCTTTGAAACAAATC 1080
Qy 361 GlyTyrGluIleAlaSerLysCysGlyGlyIleProLeuValAlaAsnAlaPheGlyLys 380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 GGGTATGAAATTGCAAGTAAATGTGGGGGTATACCACTCGTGGCAAATGCTTTCGGGAAA 1140
Qy 381 ValMetSerGlyAsnLysSerIleAlaAlaTrpGlnTyrIleLysAspArgMetValAsp 400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 GTAATGTCAGGGAATAAGTCCATCGCAGCATGGCAGTATATAAAAGATAGGATGGTTGAT 1200
Qy 401 LeuGlyLeuArgAspGluAspGlnLysAspThrLeuGluSerLeuLysLeuSerTyrTyr 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 TTGGGTTTGAGAGACGAAGATCAAAAAGACACATTAGAGTCTCTCAAGTTGAGTTATTAC 1260
Qy 421 PheMetLysLeuGluPheLysIleCysPheSerTyrLeuAlaAlaPheProLysGlyPhe 440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 TTCATGAAGCTGGAGTTCAAAATTTGTTTCTCGTATTTGGCGGCATTTCCCAAGGGCTTC 1320
Qy 441 IleIleAspThrAsnArgLeuIleGlnGlnTrpAsnAlaLeuGlyTyrIleTyrSerGlu 460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 ATTATAGACACCAACCGTTTAATCCAGCAATGGAATGCACTTGGATACATTTATTCAGAA 1380
Qy 461 HisAspGlyLysAsnCysIleAspTyrLeuLeuGlyMetSerPheLeuGlnIleSerGly 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 CATGATGGTAAAAACTGCATCGACTACCTTCTTGGGATGTCCTTTCTTCAGATTTCAGGA 1440
Qy 481 ProSerSerAlaSerGlnSerProAlaCysAlaAsnAlaSerGlyGluLeuThrMetHis 500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 CCTTCTTCGGCTAGTCAAAGTCCAGCGTGTGCCAATGCATCTGGGGAGCTTACCATGCAT 1500
Qy 501 AspLeuValHisAspLeuAlaLeuValIleThrValAspGluPheLeuValLeuAspAla 520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 GATCTGGTACATGATCTTGCGTTAGTAATTACTGTTGATGAATTCCTTGTTTTGGATGCT 1560
Qy 521 AspAlaThrGlyProArgThrTrpLysLysAlaIleHisCysArgHisAlaGluLeuIle 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 GATGCTACTGGACCAAGGACTTGGAAAAAAGCTATTCACTGCCGACATGCAGAGTTGATA 1620
Qy 541 GlnTyrLysAsnGlnSerAsnValPheGluHisLeuProLysLysLeuArgSerLeuHis 560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 CAATACAAGAATCAATCCAATGTTTTCGAGCATCTGCCGAAAAAGCTTAGATCCCTCCAT 1680
Qy 561 IleArgAspSerLeuLysTrpLysLeuProProLysAlaPheSerArgCysLysTyrMet 580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 ATTAGAGATTCACTGAAATGGAAACTCCCTCCAAAGGCCTTTTCTCGATGCAAGTACATG 1740
Qy 581 ArgValLeuAspLeuAlaCysLeuValGlyGlnLeuSerGluGlyGlnSerThrSerSer 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 CGTGTCTTGGACCTAGCATGTTTAGTAGGGCAACTCTCTGAAGGGCAATCAACGTCAAGC 1800
Qy 601 AsnMetArgLeuProArgSerIleAsnLysMetLysLeuLeuArgTyrLeuAspAlaThr 620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 AACATGAGGCTGCCACGTTCCATAAACAAAATGAAGCTACTTAGGTACCTTGATGCCACG 1860
Qy 621 GlyLeuProValSerSerLeuSerLysSerLeuHisIleLeuGlnAsnMetGluThrLeu 640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1861 GGATTGCCAGTTTCTTCACTTTCTAAGTCTTTGCATATACTTCAAAATATGGAAACTCTG 1920
Qy 641 IleMetSerAsnCysSerLeuGluThrLeuProAspAsnValCysSerLeuHisLysLeu 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1921 ATAATGTCCAATTGCTCACTTGAAACCTTGCCTGACAATGTTTGTAGCCTCCACAAACTT 1980
Qy 661 SerTyrLeuAspLeuSerGlyAsnArgSerLeuAsnLysLeuProThrSerLeuGlyLys 680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1981 AGCTATCTTGATCTGTCCGGTAATAGAAGCCTTAATAAGCTACCTACGTCGTTGGGTAAG 2040
Qy 681 LeuSerLysLeuSerPheLeuAsnLeuSerGlyCysSerValLeuGlnGlyValProLys 700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2041 CTCTCTAAGCTCTCTTTCCTCAACTTATCAGGGTGTTCCGTCCTCCAAGGGGTGCCTAAA 2100
Qy 701 SerIleCysGlnLeuThrCysLeuGlnTyrLeuAspMetSerGluCysArgAlaValGln 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2101 TCCATTTGCCAGTTGACATGTTTACAATACCTAGACATGTCAGAGTGTCGTGCCGTTCAA 2160
Qy 721 AsnLeuProAspLysPheGlySerLeuProAsnIleSerPheLeuAsnLeuSerGlyCys 740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2161 AATCTTCCTGATAAGTTTGGTAGCCTACCAAATATCTCATTCCTAAATTTGTCCGGTTGC 2220
Qy 741 SerLysLeuThrLysLeuProAspIleValAsnLeuGluSerLeuGluHisPheAspLeu 760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2221 TCAAAATTAACCAAACTACCTGACATTGTTAACCTTGAGTCTTTGGAGCATTTCGACCTA 2280
Qy 761 SerSerCysHisGluLeuLysAspLeuProGlnAspPheGlyAsnLeuGlnAsnLeuVal 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2281 TCAAGTTGCCACGAGCTAAAAGACCTCCCACAAGATTTTGGTAATCTTCAAAATCTTGTG 2340
Qy 781 PheLeuSerLeuSerAspCysTyrLysValSerValLeuProGluSerPheCysGlnLeu 800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2341 TTCTTGAGCCTCTCTGATTGCTACAAGGTTTCAGTGCTCCCGGAATCATTTTGCCAGCTT 2400
Qy 801 IleHisLeuLysTyrLeuAspLeuSerAspCysHisGlyLeuArgGluLeuProGluCys 820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2401 ATTCATTTGAAATACCTAGATCTTTCAGATTGCCATGGCCTCAGGGAACTCCCAGAGTGT 2460
Qy 821 PheGlyAsnLeuSerGluLeuAspSerLeuAsnLeuIleSerCysSerLysLeuGlnVal 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2461 TTTGGTAACCTTTCTGAGCTTGACTCATTGAACCTAATAAGTTGTTCCAAGCTGCAAGTA 2520
Qy 841 LeuProAspSerPheCysSerLeuPheLysLeuArgHisLeuAsnLeuSerTyrCysMet 860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2521 CTGCCTGACTCATTCTGTAGCTTGTTTAAGCTGAGGCATCTCAATTTGTCATACTGTATG 2580
Qy 861 ArgLeuGluLysLeuProSerSerLeuGlyAspLeuLysLeuArgLeuLeuAspIleSer 880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2581 AGGCTTGAAAAGCTCCCATCCTCGTTAGGTGACCTTAAGCTTCGGTTATTGGACATCTCT 2640
Qy 881 AlaAlaThrPheHisAspLeuProAspSerIleArgGlyMetThrThrLeuThrLysLeu 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2641 GCTGCAACTTTCCATGATTTACCGGATAGCATCCGTGGCATGACTACACTCACTAAACTT 2700
Qy 901 ValValSerThrAlaGlnLeuGlyValHisAsnLysValArgAspIleArgGlnHisLeu 920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2701 GTGGTCTCGACAGCACAACTAGGGGTTCATAACAAGGTTCGTGACATTCGGCAGCATCTG 2760
Qy 921 AsnLeuProGlyGluIleValHisThrValHisLeuThrGluAsnLysGlyCysSerSer 940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2761 AATTTGCCAGGGGAGATAGTACATACTGTACATCTGACTGAAAACAAAGGATGTAGCAGT 2820
Qy 941 IleValGluLeuAlaGlnLeuThrCysGlnAsnLeuLysValLeuGlnLeuGlnAsnVal 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2821 ATTGTAGAGTTAGCACAATTGACCTGTCAAAACTTGAAAGTCTTACAACTTCAGAATGTC 2880
Qy 961 ArgHisProGluAspAlaGluArgAlaLysLeuArgAspLysSerAspLeuArgValLeu 980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2881 AGGCATCCGGAAGATGCAGAGAGAGCCAAGTTACGTGATAAATCAGATCTTCGGGTTCTA 2940
Qy 981 TrpLeuCysTrpGlyLeuGlnArgGluGluAspIleTyrValLeuGluArgLeuValPro 1000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2941 TGGCTTTGTTGGGGACTCCAGCGAGAAGAGGATATTTATGTGCTGGAGAGGCTTGTACCT 3000
Qy 1001 ProArgAsnLeuGluHisPheThrLeuAspGlyTyrMetSerLysAspPheProAsnTrp 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3001 CCACGCAATCTTGAACATTTTACGCTAGATGGGTATATGAGCAAGGATTTCCCTAACTGG 3060
Qy 1021 IleSerHisIleSerThrTyrLeuProTyrLeuThrPheLeuThrLeuCysAsnLeuGly 1040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3061 ATTTCTCACATCTCCACATACCTTCCTTATCTCACCTTTCTCACCCTTTGCAATTTAGGA 3120
Qy 1041 AlaCysAspAsnLeuProProPheGlyGlnLeuProAsnLeuArgCysLeuGluMetAsn 1060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3121 GCATGTGATAATCTTCCACCATTTGGGCAACTGCCAAATTTAAGATGTCTAGAGATGAAT 3180
Qy 1061 TyrIleProAsnIleThrLysIleGlyLysGluPheTyrGlyGluGlyGlyThrCysArg 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3181 TATATTCCTAACATCACAAAAATTGGCAAGGAATTCTATGGAGAAGGTGGAACCTGTAGG 3240
Qy 1081 LysLeuArgSerIleGlnLeuLysSerMetGluAsnLeuValGluTrpTrpThrAlaLeu 1100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3241 AAATTAAGAAGTATACAATTGAAGTCAATGGAGAATTTGGTGGAATGGTGGACTGCACTC 3300
Qy 1101 SerGlyGluLysAsnGluGluSerLeuIleProAsnLeuHisCysLeuSerIleArgAsn 1120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3301 TCAGGTGAGAAAAATGAAGAGTCACTGATCCCTAATTTGCATTGTTTGTCAATAAGGAAC 3360
Qy 1121 CysProLysLeuLysPheLeuProTyrProProArgSerMetPheTrpHisLeuAspAsn 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3361 TGCCCCAAGTTGAAGTTCCTACCATATCCCCCGAGGAGTATGTTTTGGCACTTGGATAAT 3420
Qy 1141 SerSerMetValSerProLysGluGlyPheGlyLysLeuSerSerTyrAlaPheProPhe 1160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3421 AGCAGCATGGTTTCGCCAAAAGAGGGATTTGGAAAGCTTTCTTCTTACGCTTTTCCTTTT 3480
Qy 1161 LeuMetValValArgAsnCysAsnPheAlaProAspLysTrpAspTrpLeuGlnHisLeu 1180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3481 CTCATGGTAGTAAGAAACTGCAACTTTGCTCCAGACAAATGGGATTGGCTTCAACACCTC 3540
Qy 1181 ProThrLeuGluIlePheTyrValGluSerIleAsnGlyLeuArgAlaLeuProGluAla 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3541 CCCACCCTTGAGATATTTTATGTTGAGAGCATCAATGGCTTGAGGGCATTGCCAGAGGCC 3600
Qy 1201 MetGlnCysLeuAsnSerLeuThrArgLeuAsnLeuTrpSerLeuLysAspLeuGluLys 1220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3601 ATGCAATGTTTAAACTCTCTCACAAGACTAAATTTGTGGTCATTAAAGGACCTGGAGAAA 3660
Qy 1221 LeuProGluTrpLeuGlyAspLeuThrSerLeuGluTyrIleHisIleLysAspCysPro 1240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3661 CTGCCAGAATGGTTGGGGGACCTCACTTCTCTAGAATACATTCACATCAAAGATTGTCCC 3720
Qy 1241 MetValThrSerLeuProValArgMetLysCysLeuAlaAlaLeuArgGluLeuCysLeu 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3721 ATGGTGACATCTTTGCCTGTAAGAATGAAGTGTCTTGCTGCTCTTAGAGAACTTTGCCTG 3780
Qy 1261 AlaGluCysArgGlyLeuGluValLeuProGluTrpLeuGlyHisLeuThrSerLeuGln 1280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3781 GCGGAGTGCAGAGGCCTAGAAGTATTGCCAGAATGGCTGGGACATCTGACTTCCCTACAA 3840
Qy 1281 GluPheTyrIleMetSerCysProAsnLeuThrSerLeuProGluSerMetLysCysLeu 1300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3841 GAGTTCTATATCATGAGTTGCCCCAACCTGACTTCCTTGCCTGAAAGCATGAAGTGTCTT 3900
Qy 1301 ThrAlaLeuArgValLeuArgLeuMetGluCysGluGlyLeuGluValLeuProGluTrp 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3901 ACTGCTCTCAGAGTACTTCGGCTGATGGAGTGCGAAGGCCTAGAAGTATTGCCAGAATGG 3960
Qy 1321 LeuGlyHisLeuThrSerLeuGlnGluPheTyrIleIleArgCysProAsnLeuThrSer 1340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3961 CTGGGACATCTCACTTCCCTACAAGAGTTCTATATCATCCGTTGCCCCAACCTGACTTCT 4020
Qy 1341 LeuProLysSerMetLysCysLeuThrAlaLeuArgValLeuTrpLeuThrGluCysGlu 1360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4021 TTGCCTAAAAGCATGAAGTGTCTTACTGCTCTCAGAGTACTTTGGCTGACGGAGTGCGAA 4080
Qy 1361 GlyLeuGluValPheProGluTrpLeuGlyHisLeuIleSerLeuGlnGluPheTyrIle 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4081 GGCCTAGAAGTATTCCCAGAATGGCTAGGACATCTCATTTCCCTACAAGAGTTTTACATC 4140
Qy 1381 ThrCysCysSerAsnLeuThrCysLeuProValSerMetLysArgLeuThrAlaLeuArg 1400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4141 ACCTGTTGCTCCAACCTGACTTGTTTGCCTGTAAGCATGAAGCGTCTTACTGCTCTGAGA 4200
Qy 1401 LeuLeuTrpLeuGlyGlnCysGluGlyLeuAspValLeuProGluTrpLeuGlyGlnLeu 1420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4201 TTACTCTGGTTGGGCCAGTGTGAAGGTCTAGACGTATTGCCAGAATGGTTGGGACAGCTC 4260
Qy 1421 IleSerLeuGlnGluPheAsnIleValGlyCysProAsnLeuThrHisPheProGluSer 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4261 ATCTCCCTTCAAGAATTTAACATCGTCGGTTGCCCGAACTTGACACATTTTCCTGAAAGC 4320
Qy 1441 ThrArgAsnLeuThrAlaLeuLysLysLeuAsnIleTrpGlyCysProSerLeuValGlu 1460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4321 ACACGGAACCTTACCGCCTTGAAGAAACTGAATATTTGGGGATGTCCGAGTCTTGTTGAG 4380
Qy 1461 ArgCysGlnGlyGluAspAlaAspLeuIleSerHisIleProGluValLeuLeuGluGly 1480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4381 AGGTGCCAAGGGGAGGATGCTGACCTGATTTCTCATATCCCGGAAGTCTTGTTAGAAGGA 4440
Qy 1481 LysThrArgGluLeuTrpSerThrSerGlyAspAlaGluAlaSerThrSerGlyAlaSer 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4441 AAAACTAGAGAATTGTGGTCGACTTCCGGAGATGCTGAAGCATCGACTTCCGGAGCATCG 4500
Qy 1501 ThrAlaGluGluAlaGlyProSerThrSer 1510
||||||||||||||||||||||||||||||
Db 4501 ACTGCTGAAGAAGCTGGACCATCGACTTCT 4530
The pDEST2BL vector comprising the NLR coding sequence of Moscou SEQ ID NO: 25 reads on a DNA construct comprising an isolated polynucleotide encoding a polypeptide comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 1 and further comprising at least one plant compatible expression regulatory element (instant claim 61). Additionally, the plant chromosome where the transgene sequence was inserted reads on a DNA construct comprising the polynucleotide and further comprising at least one plant compatible expression regulatory element.
The wheat plants transformed with the cDNA with 99% identity to instant SEQ ID NO: 3, encoding the NLR with 100% identity to instant SEQ ID NO: 1 reads on a Triticeae plant comprising at least one cell comprising a heterologous polynucleotide of instant claims 1 & 6, and the heterologous polynucleotide is capable of conferring resistance to wheat leaf rust, which is in the genus Puccinia (instant claims 20-21), which reads on enhanced tolerance compared to a plant devoid of the polynucleotide (instant claim 15). The seeds collected anticipate the seed of instant claim 25 comprising a heterologous polynucleotide.
The method of transforming the wheat plant of Moscou anticipates the method of making the Triticeae plant of instant claims 26, 28, 34, & 35 comprising introducing a heterologous polynucleotide encoding the amino acid sequence of instant SEQ ID NO: 1 into a susceptible Triticeae plant. The method of screening multiple plants and phenotyping based on a score, disclosed by Moscou, anticipates the method of instant claims 39, 46 & 47, comprising providing a plurality of plants of instant claim 1 and selecting a plant showing resistance compared to a pre-determined resistance score value. Instant claim 40, which further limits the control plant, is also anticipated, and claim 41, which requires selecting the plant by inoculating with the fungus and selecting a phenotypically resistant plant is anticipated.
Claim Rejections - 35 USC § 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, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 43, 45-47 & 61 are rejected under 35 U.S.C. 103 as being unpatentable over Moscou et al US 2024/0218356 A1 (published 7/4/2024 with a priority date of 5/11/2021; hereafter Moscou) in view of Millet et al US 2016/0222406 A1 (published 8/4/2016, hereafter Millet).
Claim(s) 1, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 43, 45-47 & 61 are drawn to a Triticeae plant comprising a heterologous polynucleotide encoding a polypeptide having at least 80% identity to the amino acid sequence set forth in SEQ ID NO: 1 capable of conferring tolerance to at least one rust disease, a method for producing the plant, and a method for selecting a plant comprising providing a plurality of such plants.
The teachings of Moscou are presented above. In addition, Moscou teaches that RNA sequencing can be used to assess relative expression levels of NLR genes and identify genes expressed in plant parts (paragraph [0227]). Moscou teaches that an NLR is expressed in a plant if mRNA is detected in the plant (paragraph [0318]). Moscou teaches that for RNAseq, PCR primers were developed that comprised the first nucleotides of the start or end of the coding sequence (paragraph [0230, 0351-0352]).
Moscou SEQ ID NO: 25 comprises sequences identical to instant SEQ ID NO: 42 and 43 and in opposite orientations. See alignments below.
SEQ ID NO: 42 (top) vs Moscou SEQ ID NO: 25
Score
Expect
Identities
Gaps
Strand
60.0 bits(30)
9e-14
30/30(100%)
0/30(0%)
Plus/Plus
Query 1 TAATCAAACTCCTCGAAGATGAGACCACTA 30
||||||||||||||||||||||||||||||
Sbjct 59 TAATCAAACTCCTCGAAGATGAGACCACTA 88
SEQ ID NO: 43 (top) vs Moscou SEQ ID NO: 25
Score
Expect
Identities
Gaps
Strand
58.0 bits(29)
3e-13
29/29(100%)
0/29(0%)
Plus/Minus
Query 1 CCAGCAGGTCCTCAACGTCGTGGGAGATG 29
|||||||||||||||||||||||||||||
Sbjct 262 CCAGCAGGTCCTCAACGTCGTGGGAGATG 234
Moscou does not teach selecting a plant resistant to the rest disease by detecting the presence of the heterologous polynucleotide within the genetic material of the at least one cell of the plant by amplifying at least one marker by a pair of primers.
Millet teaches a method of producing wheat cultivars resistant to leaf rust or stripe rust comprising a chromosome segment of Ae. sharonensis (abstract). Millet teaches the production of resistant lines by introgression to produce homozygous resistant lines and detecting markers (paragraph [01440145]). Millet teaches that selecting plants resistant to rust disease is performed by detecting the presence of the Ae. sharonensis resistant conferring segment within the genome of the wheat plant, which can be done by any method in the art including identifying markers on the chromosome (paragraph [0046]). DArT analysis to detect markers in the wheat genome is taught by Millet (paragraph [0153]). Millet teaches using markers to reduce the size of the resistance introgression (paragraphs [0156-0157]) as well as for employing marker-assisted selection to select resistant plants during introgression (paragraph [0120]). Millet suggests that marker-assisted selection can be combined with resistance phenotypic selection (paragraph [0120]).
Millet also suggests an embodiment of introducing a genetic element comprising the resistance segment by introducing the segment into a susceptible wheat cultivar, that resistant donors may be identified by DNA markers, and that the introduction may be by transformation (paragraphs [0092-0096]).
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 Moscou to include the detection of the resistance locus in the genetic material of the plant, as taught by Millet. One of ordinary skill in the art would have been motivated to use primers to detect the locus in the plants, because marker-assisted selection was known to be an alternative to phenotypic selection for resistant wheat plants. One of ordinary skill in the art would have had reasonable expectation of success, because marker assisted selection was routine in the art prior to the filing of the instant application, and Moscou teaches primers for amplifying the coding sequences of the NLR gene already. Thus, using primers identical to/or complementary to Moscou SEQ ID NO: 25, such as instant SEQ ID NOs: 42 & 43, to detect the presence of the resistance heterologous nucleotide in transformed wheat plants and select resistant plants (instant claims 43 & 45) would have been obvious over Moscou and Millet.
Claims 1, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 46-47 & 61 are also obvious as presented above.
Claim(s) 1, 3, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 46-47 & 61-62 are rejected under 35 U.S.C. 103 as being unpatentable over Moscou et al US 2024/0218356 A1 (published 7/4/2024 with a priority date of 5/11/2021; hereafter Moscou) in view of Li et al (2015) Current Opinion in Immunology. 32:114–121 (published 2/6/2015, hereafter Li).
Claims 3 & 62 are drawn to the Triticeae plant wherein the heterologous polynucleotide comprises a nucleic acid sequence having at least 70% identity to SEQ ID NO: 6 over the entire length of the polynucleotide or a DNA construct having at least 70% identity to the nucleic acid sequence set forth in SEQ ID NO: 6.
The teachings of Moscou are presented above. Moscou teaches that Aegilops longissima is expected to comprise one or more effective NLR resistance genes against one or more pathogens (paragraph [0242]) and was used for preparation of libraries of candidate NLR genes (paragraph [0345]). Moscou teaches the cloning of NLR genes via amplification with primers (paragraphs [0350-0352]). Moscou also teaches that the proportion of NLRs is variable according to species, guided by the available diversity of accessions in each species (paragraph [0352]). Moscou teaches assaying NLR genes, including NLR genes from Ae. longissima, for resistance to rust diseases by transforming wheat plants (paragraphs [0351-0362]).
Moscou does not teach a sequence with 70% identity to instant SEQ ID NO: 6.
Li teaches that regulation of plant NLRs at the levels of transcription and RNA processing is important, because over-accumulation can lead to autoimmunity or dwarf phenotypes, and insufficiency of expression can lead to susceptibility (page 115, right column, paragraph 4). Li also teaches that alternative splicing can be a crucial step in the regulation of NLR gene expression (page 117, left column, paragraph 2).
Before the filing of the instant invention, one of ordinary skill in the art would have been motivated to follow the method of Moscou to discover and clone additional NLR genes in Ae. longissima capable of conferring resistance. One of ordinary skill in the art would have been motivated to clone additional NLR genes in Ae. longissima accessions, because that species was expected to comprise one or more effective NLR resistance genes and that NLRs are variable according to the diversity of accessions available in the species. One of ordinary skill in the art would have had reasonable expectation of success, because a gene encoding a protein identical to the gene encoded by instant SEQ ID NO: 6 had already been identified in the species Ae. sharonensis and had been shown to provided resistance to leaf rust in wheat.
Furthermore, one of ordinary skill in the art would have been motivated to clone the genome sequence of the NLR gene, rather than the coding sequence as Moscou does, because it was known in the art prior to the filing of the instant application that regulation of transcription and RNA processing is important to NLR expression and plant immunity. Cloning the coding sequence, without introns, would prevent alternative splicing, if applicable to the instant gene, or alter RNA processing. One of ordinary skill in the art would have had reasonable expectation of success in cloning the genomic sequence, because Moscou taught the design of primers for isolating the coding sequence of a gene with 99% sequence identity to the coding sequence of instant SEQ ID NO: 6 (instant SEQ ID NO: 3, see alignment above). One of ordinary skill in the art would have expected that primers capable of isolating the coding region would serve to isolate the genomic sequence of the gene.
Instant SEQ ID NO: 6 is the genomic sequence of the Ae. longissima NLR gene (as described in the instant specification, page 43, lines 3-4) encoding a polypeptide identical to the Ae. sharonensis polypeptide of Moscou SEQ ID NO: 26. Thus, although the genomic sequence of instant SEQ ID NO: 6 was not known in the art prior to the filing of the instant application, it would have been obvious to follow the method of Moscou to arrive at a construct comprising a polynucleotide sequence having at least 70% identity to SEQ ID NO: 6 (claim 62) or to use such a polynucleotide sequence in the method of Moscou to introduce the polynucleotide into a plant (claim 3).
Claims 1, 6, 15, 20-21, 25-26, 28, 34-35, 39-41, 46-47 & 61 are also obvious over Moscou as presented above.
Conclusion
No claims are allowed.
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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