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 .
Claim Status
Claims 1-3, 5, 7-8, 12-16 and 18-20 are pending. Claims 4, 6, 9-11 and 17, are canceled. Claims 1-3, 5, 7-8, 12-16 and 18-20 are examined in the instant application.
All previous rejections not set forth below have been withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Response to Amendments
Status of Rejection from action
In regard to Claim 15 rejected under 112(b) is withdrawn in view of amendment, because Applicant added introducing step.
Claim Rejections - 35 USC § 101
Claims 1-3, 5, 8, 12-13, 16 and 18-20 REMAIN rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring product and a natural phenomenon without significantly more. The claim(s) recite(s) “A downy mildew resistance lettuce plant, wherein said lettuce plant comprises a V06 resistance gene”. This judicial exception is not integrated into a practical application because the V06 resistance gene is a naturally occurring protein. As described in MPEP § 2106, subsection III, Step 2A of the Office’s eligibility analysis is the first part of the Alice/Mayo test, i.e., the Supreme Court’s "framework for distinguishing patents that claim laws of nature, natural phenomena, and abstract ideas from those that claim patent-eligible applications of those concepts." Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217-18, 110 USPQ2d 1976, 1981 (2014) (citing Mayo, 566 U.S. at 77-78, 101 USPQ2d at 1967-68).
The claim(s) do not include additional elements that are sufficient to amount to significantly more than the judicial exception because:
In regard to claims 1 and 18, the claims are directed to a resistance gene present in a downy mildew resistant lettuce plant. Applicant states “[g]ene mapping experiments were done to identify a resistance gene that is involved in full spectrum Bremia (B. lactucae) resistance in lettuce (L. sativa). The resistance gene was originally isolated from L. virosa and was mapped on chromosome 8”, (see page 8 lines 19-21).
For example, UniProt et al. (A0AAU9MS05_9ASTR GenBank: CAH1424770.1. 2024 (previously cited)) having 100% sequence identity to Applicants SEQ ID NO: 3 is a naturally occurring protein, (see search result below). SEQ ID NO: 3 inherently does not comprise SEQ ID NOs: 6 and 7 and produces and average of at least 5 g or seed per lettuce plant.
ID A0AAU9MS05_9ASTR Unreviewed; 1318 AA.
AC A0AAU9MS05;
DT 27-NOV-2024, integrated into UniProtKB/TrEMBL.
DT 27-NOV-2024, sequence version 1.
DT 08-OCT-2025, entry version 5.
DE RecName: Full=TIR domain-containing protein {ECO:0000259|PROSITE:PS50104};
GN ORFNames=LVIROSA_LOCUS11951 {ECO:0000313|EMBL:CAH1424770.1};
OS Lactuca virosa.
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Cichorioideae; Cichorieae;
OC Lactucinae; Lactuca.
OX NCBI_TaxID=75947 {ECO:0000313|EMBL:CAH1424770.1, ECO:0000313|Proteomes:UP001157418};
RN [1] {ECO:0000313|EMBL:CAH1424770.1, ECO:0000313|Proteomes:UP001157418}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Xiong W., Schranz E.;
RL Submitted (JAN-2022) to the EMBL/GenBank/DDBJ databases.
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:CAH1424770.1}.
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DR EMBL; CAKMRJ010001889; CAH1424770.1; -; Genomic_DNA.
DR Proteomes; UP001157418; Unassembled WGS sequence.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0043531; F:ADP binding; IEA:InterPro.
DR GO; GO:0006902; P:defense response; IEA:UniProtKB-KW.
DR GO; GO:0051707; P:response to other organism; IEA:UniProtKB-ARBA.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR FunFam; 3.40.50.10140:FF:000007; Disease resistance protein (TIR-NBS-LRR class); 1.
DR Gene3D; 1.10.8.430; Helical domain of apoptotic protease-activating factors; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 3.
DR Gene3D; 3.40.50.10140; Toll/interleukin-1 receptor homology (TIR) domain; 1.
DR InterPro; IPR042197; Apaf_helical.
DR InterPro; IPR044974; Disease_R_plants.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR055414; LRR_R13L4/SHOC2-like.
DR InterPro; IPR002182; NB-ARC.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR InterPro; IPR036395; WH_DNA-bd_sf.
DR PANTHER; PTHR11017:SF544; ADP-RIBOSYL CYCLASE_CYCLIC ADP-RIBOSE HYDROLASE; 1.
DR PANTHER; PTHR11017; LEUCINE-RICH REPEAT-CONTAINING PROTEIN; 1.
DR Pfam; PF23598; LRR_14; 2.
DR Pfam; PF00931; NB-ARC; 1.
DR Pfam; PF01582; TIR; 1.
DR Pfam; PF23282; WHD_ROQ1; 1.
DR PRINTS; PR00364; DISEASERSIST.
DR SMART; SM00369; LRR_TYP; 5.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52058; L domain-like; 2.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1.
DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR PROSITE; PS50104; TIR; 1.
PE 4: Predicted;
KW Leucine-rich repeat {ECO:0000256|ARBA:ARBA00022614};
KW Membrane {ECO:0000256|SAM:Phobius}; NAD {ECO:0000256|ARBA:ARBA00023027};
KW Plant defense {ECO:0000256|ARBA:ARBA00022821};
KW Reference proteome {ECO:0000313|Proteomes:UP001157418};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Transmembrane {ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|SAM:Phobius}.
FT TRANSMEM 1296..1316
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 13..176
FT /note="TIR"
FT /evidence="ECO:0000259|PROSITE:PS50104"
FT REGION 1201..1240
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1204..1218
FT /note="Low complexity"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1220..1234
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1318 AA; 149817 MW; 2AA99AA511E185AF CRC64;
MASSSSSSNQ KSFKYQVFLS FTGEDTRKTF VDHLYASLKQ KGIHTFRDNE ELEKGKRIDE
LFKAIEESRF FIIVFSKNYA SSSWCLKEVT KIMECQDGNQ QIAYPLFYGV EPSDIRHQTG
PVGRAIA KHK DNEQIKKWEK ALEDAGNLVG WDLKNIANGH EAEAITKIIE EISLKLGSIH
LGNDEHLIGM ERRMQALEPS LGIGLNDKAR MIGIKGMGGI GKTTLAKAIF NKFSSHFEGS
SFVADIREVS KKKGLESLQQ QILSDVLKDE RMRVGSVNEG ERIMRMRLPY KKVLLVLDDV
DDTKQLEALA GDWFKNGSRI IITTRDENVL LSHEVKKKWI HDVDFLSDEE AIRLFLWFAF
RRYIPDQGYE ELTARVVRYA AGLPLKIRVL GSHLCGENKD VWRDALKRLE KIPLQETLDV
LEISYNSLED DHKEIFLDVA CFLNGLSHEF AIRILESCGF HATYGLRILE HKSLVTISDG
RLGMHDTIQE LGKNIIRREH PRELNKHSRL WNTEEIVELL SDDEGTATST CTGMLLLLLL
CELSPEIIIQ KLGNLKRLRY LCVLGIVSDC FPSDWKFDET KPSFPNSLQY LIWDKYPGFS
LPHTFRAKNL VGLELTGSRI TQLWESSERK KLKFFLLGNS NLRTLRESGE RMVLEKLRFL
NLKNSKVSIL DLGMTPNLER LDLEGCHDLK EIYAPAGCLK RLIYIDLRGC PWSVSFPFVK
QLEPHVLLSL PVLAVKVDPM EAFPRDSTNN LRFTFVYYKE LPSSREGINF KSVFLDLQPC
TKLESVSGSI CGLQHLREVK FQGCIPEVPK DIDQLKGLQQ LILLSTHVKR LPDSVCMLKH
LKSLKLSDCQ HLEELPENLG LLENLEELSL STASIRRLPD SVCMLKHLKS LKLGDCQHLE
ELPENLGWLG NLEELMFISI SIRRLPDSIC MLSHLKSLHL DSCGRLEKLP EDIGQLKSLE
MLNLGQCESL RDIPNSICNM KSLTHLYLRE CRQVEKLPED LGNLKLLQGL NIGFTGISHL
PHSISSMNGL LVFGSISLLQ SCAFATEIYT HEVLGPHCRI QAMDSTLAHT ELRSQSEQKY
LTREGKEILI EDGDEGTLGG ESSDDVNKRM RVSHMGTNSE YLQNKELIRF FENLMSAADP
EEFLKMLQVI TSLQGDNNGS SEMSEKETDM IIKMLAEELQ NRSEMASSFN TQNLVETNRS
NIPQGQQSQR SGTSQGQGFL NRQPSFPNIQ SQLRNPDMRE MTPDIKFSRE DAERAQQVMS
SLSPETIHRL IKLADLIKTA CEGAVKTKNW LLGRQGFVMV VCMLLFAIFL HWLGFIGN
In regard to claims 2-3, the claims are directed to a V06 resistance gene comprising a nucleic sequence having at least 95% sequence identity with SEQ ID NO: 1. As mentioned by the Applicant said gene is found in resistant lettuce plant (see page 8 lines 19-21). Therefore, the naturally occurring V06 nucleic acid is found in nature and not patent-eligible.
For example, NCBI et al. (PREDICTED: Lactuca sativa TMV resistance protein N (LOC111911229), transcript variant X2, mRNA NCBI Reference Sequence: XM_023957009.3. 2022 (previously cited)) having 95.07% sequence identity to Applicants SEQ ID NO: 1 is a naturally occurring protein, (see search result below).
LOCUS XM_023957009 2327 bp mRNA linear PLN 22-DEC-2022
DEFINITION PREDICTED: Lactuca sativa TMV resistance protein N (LOC111911229),
transcript variant X2, mRNA.
ACCESSION XM_023957009
VERSION XM_023957009.3
DBLINK BioProject: PRJNA432228
KEYWORDS RefSeq.
SOURCE Lactuca sativa (garden lettuce)
ORGANISM Lactuca sativa
Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae;
Pentapetalae; asterids; campanulids; Asterales; Asteraceae;
Cichorioideae; Cichorieae; Lactucinae; Lactuca.
COMMENT MODEL REFSEQ: This record is predicted by automated computational
analysis. This record is derived from a genomic sequence
(NC_056630) annotated using gene prediction method: Gnomon,
supported by EST evidence.
Also see:
Documentation of NCBI's Annotation Process
On Dec 22, 2022 this sequence version replaced XM_023957009.2.
##Genome-Annotation-Data-START##
Annotation Provider :: NCBI RefSeq
Annotation Status :: Full annotation
Annotation Name :: GCF_002870075.4-RS_2022_12
Annotation Pipeline :: NCBI eukaryotic genome annotation
pipeline
Annotation Software Version :: 10.1
Annotation Method :: Best-placed RefSeq; Gnomon;
cmsearch; tRNAscan-SE
Features Annotated :: Gene; mRNA; CDS; ncRNA
##Genome-Annotation-Data-END##
FEATURES Location/Qualifiers
source 1..2327
/organism="Lactuca sativa"
/mol_type="mRNA"
/cultivar="Salinas"
/db_xref="taxon:4236"
/chromosome="8"
gene 1..2327
/gene="LOC111911229"
/note="TMV resistance protein N; Derived by automated
computational analysis using gene prediction method:
Gnomon. Supporting evidence includes similarity to: 1 EST"
/db_xref="GeneID:111911229"
CDS 201..2069
/gene="LOC111911229"
/codon_start=1
/product="disease resistance protein RPV1 isoform X2"
/protein_id="XP_023762777.1"
/db_xref="GeneID:111911229"
/translation="MTPNLERLGLERCRDLEKIYAPAGCLKRLIYIDLRGCPWSVSFP
FVKQLEPHVLLSLPVLAVKVDPLEDFPKDHTNNLRFTFVYYKEPPLSREGIDYKTVFL
DLQPCTKLESVSGSICGLQHLREVKFQGCITEVPNDIDQLKSLEQLILLSTHVKRLPD
SVCMLKHLKSLNISDCQHLEELPENLGLLENLMELSLSTTSIQRLPDSVCMLKNLKSL
ELGDCQHLEELPENLGWLGNLEELVFISINIRRIPDSICMLSHLKSLHFDSCGGLEKL
PEDIGQLESLEMLNLGKCESLRDIPNSLCNMKSLNHLYLRECRQVEKLPEDLGNLKLL
QGLNIAFTGISHLPHSISSMNGLHVFGSISLLQSCAFATEIYTHEVLGPHCRIQAMDS
TLARTELRSQSTQKYLTREGKEILIEDGDEGTPGEGILCFFFQVKFFIDQHVCILLLH
LVCISESSEYLQNQELIRFLENFMPAPEPEDLENMLQVITSFQGDNNGSSEMSEKETD
MIIMMLNEELQKRSEMASSFNTQNPMETNRSNIPQSQLTNPDMREEDAERAQQVMSSL
SPETIDRLIKLADRIKTACEGAVKTKNWLLGRQGFLMVVFMLLFAIFLHWLGFIGN"
polyA_site 2327
/gene="LOC111911229"
/experiment="COORDINATES: polyA evidence [ECO:0006239]"
ORIGIN
1 cgaattcgtt acagtatctg atataggata aataccctgg tttctcttta ccccacacat
61 ttcgagcaaa gaatcttgtt ggacttgaat tgactggaag caaaatcaca caactatggg
121 aaagtagaga aagaaaggtt cttgagaaac tcaggttcct cgaccttaaa aattcgaagg
181 tgaggaccct tgaccttggg atgactccca atcttgagag gttaggtctt gaaagatgtc
241 gtgatttgga aaagatttat gcgcctgctg gatgtctaaa aaggcttatc tacatagatt
301 tacgtggttg cccatggtct gtatcttttc cttttgttaa acaattggaa ccacatgtgc
361 ttcttagtct acctgtgtta gctgtgaaag tggatccctt ggaggatttt ccaaaggacc
421 acacaaacaa tctacgattt acatttgtat attataaaga accacctttg tcaagagaag
481 gaattgatta taagactgtt tttctagatc ttcagccttg cacaaaactt gagagtgttt
541 caggaagcat ttgtggctta caacatctaa gagaagttaa atttcagggc tgtattacgg
601 aggttcctaa cgacattgac cagttgaaaa gcttggaaca actcattttg ttgtctacac
661 acgtcaaacg tcttcctgat agtgtttgta tgttgaaaca tttgaaatct ctcaacatta
721 gtgattgcca gcatcttgaa gagttgccgg agaatcttgg tttgttagaa aatttaatgg
781 agctgagttt atcgactaca agtattcagc gtcttcctga tagtgtttgt atgttgaaaa
841 atctgaaatc tctcgaactt ggagattgcc aacatcttga agagttaccg gagaaccttg
901 gctggttagg aaatttagag gagctggtgt tcatttctat aaatattaga cgtattccag
961 atagcatttg catgctgagt catctgaaat ctctacactt tgactcttgt ggaggcctcg
1021 agaagttacc cgaggatatt gggcaactag agagtttaga gatgctgaac ctaggaaagt
1081 gtgaatcttt acgagatatt ccaaacagcc tctgtaacat gaaatcttta aatcatctct
1141 atctccgcga atgtagacaa gttgagaaat tgccagagga tttgggaaac ctaaagcttt
1201 tacaagggtt aaatatagcg tttacaggaa taagtcatct tccacatagt atttcctcga
1261 tgaatggtct acatgttttc ggatccatat cacttcttca gtcttgtgct tttgcaaccg
1321 agatatatac ccatgaagta cttggacccc actgccgcat acaagccatg gatagcacac
1381 tggcacgcac agaattaagg agccagtcca ctcagaagta tcttaccagg gagggcaagg
1441 aaatattaat tgaagatggt gatgagggta caccaggaga aggtattttg tgtttttttt
1501 ttcaagtcaa gttttttatt gaccaacatg tatgtattct tttgttacat cttgtatgta
1561 tttcagaatc ttcagagtat ctgcagaacc aagaactcat cagattcttg gagaacttca
1621 tgcctgcacc agaaccagaa gatttagaaa atatgctcca agtgatcacc tcctttcaag
1681 gtgacaacaa tggttcttca gaaatgagtg aaaaggaaac tgacatgata attatgatgc
1741 taaatgaaga gctccaaaag aggtctgaaa tggcatcatc tttcaacact caaaatccaa
1801 tggaaacaaa taggagtaat attccacaaa gccaattgac gaatccagac atgcgtgagg
1861 aggatgcaga aagagcccaa caagtcatgt cgtctttgtc accggagacc atcgatagac
1921 tgataaagtt ggctgatcga ataaaaacag catgtgaagg tgctgtaaaa accaaaaatt
1981 ggcttctggg gaggcagggg tttcttatgg tcgtatttat gcttcttttt gcaatctttc
2041 tccattggct tggattcatt ggcaattaga aaaaaaaaaa gaaaaaaggt aatggaatga
2101 catgtaaaaa cagtcactta attaatgctc ttgaatttaa attttggata ggtaaatcat
2161 gggcatgcgt ggctggattt tatgaattat tttggaacaa tgagtcaaac tgtcaatgtt
2221 ttatatactt tcatgacctt atgtaaccta tatcaaaata tatttcaatt attgtatgat
2281 gcattatgat taaacataaa gatatttata cactacatct tggaatc
In regard to claims 8 and 16, the claims are drawn to a plant with said resistance gene not comprising SEQ ID NOs: 6 and 7, wherein the lettuce plant produces an average seed yield of at least 5 grams (g). Additionally, the specification states “[a] Bremia resistant lettuce plant which does not comprise both markers SEQ ID No.6 and SEQ ID No.7 and/or comprises markers 1 and 2 (SEQ IDs 4 and 5, respectively) provided the most reduced V06 introgression fragment, and therefore is expected to restore the seed production to wild type levels, i.e. average weight of 15.7 g per plant” (see page 10 lines 11-14), suggesting that it is indistinguishable from the wild-type especially since said gene exist in the wild-type and produce the same amount of seed yield.
Therefore, there is nothing that would distinguish said plant from the wild-type since crossing and natural selection happens in the wild. Furthermore, beside genotyping the gene the making of the plant had no hand of man to make such plant.
In regard to claim 5, as stated above said gene is found in nature and therefore inherently is resistant to races B1:1-15EU.
In regard to claims 12-13 and 19-20, the claims are drawn to a method of identifying a downy mildew resistant lettuce plant. Step 1 asks are the claims to a process, machine, manufacture, or compositions or matter. Here, the claims are drawn to a process/method.
Step 2A asks are the claims directed to a law of nature, a natural phenomenon (product of nature), or an abstract idea? In this case the judicial exception is the V06 resistance gene that naturally is resistant against downy mildew. Additionally, the step of establishing the presence of the V06 resistance gene in a genome of the lettuce plant involves a natural phenomenon; the gene inherently confers resistance. This also represents a naturally occurring correlation between the gene and resistance. Applicant has not claimed a practical application or use of said correlation.
Step 2B asks does the claim recite additional elements that amount to significantly more that the judicial exception? Here, the claims do not recite additional elements that amount to “significantly more” than the judicial exception.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed invention is directed to naturally-occurring nucleic acid(s) and protein(s). The claimed nucleic acids, proteins, and plant(s) have the inherent property/ies that are recited in the claims.
The judicial exception is not integrated into a practical application because the claimed invention is directed to naturally-occurring nucleotides, cells, organisms, and processes. A claim that focuses on use of a natural principle must also include additional elements or steps to show that the inventor has practically applied, or added something significant to, the natural principle itself. Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. __, 132 S.Ct. 1289,101 USPQ2d 1961 (2012), at 1966. To show integration, the additional elements or steps must relate to the natural principle in a significant way to impose a meaningful limit on the claim scope.
The claimed products are not patent-eligible pursuant to the Supreme Court decision in Ass'n. for Molecular Pathology v. Myriad Genetics (formerly v. USPTO), 653 F.3d 1329, 99 USPQ2d 1398 (Fed. Cir. 2011), cert. granted, judgment vacated and remanded to the Court of Appeals for the Federal Circuit, No. 11-725, 80 U.S.L.W. 3380, 2012 BL 72224 (U.S. Mar. 26, 2012), reversed, ---- S.Ct. ----, 106 USPQ2d 1972, 1974-75 (2013). The claimed invention does not rise to a level that is markedly different in structure from what exists in nature. See “The 2019 Revised Patent Subject Matter Eligibility Guidance”, issued January 7, 2019, available from the USPTO website at https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf.
Response to Arguments
Applicant's arguments filed 04/23/2026 have been fully considered but they are not persuasive. While Applicants argument rely on that SEQ ID NO: 3 is not naturally found in Lactuca sativa, however the Sequence listing indicates SEQ ID NO: 3 is from L. sativa. Thus, Applicant’s arguments are not commensurate in scope with what is claimed, and the claimed invention is a product of nature.
Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 112(a)(Written Description)
Claims 1-3, 5, 7-8, 12-16 and 18-20 REMAIN rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description requirement may be satisfied through sufficient description of a representative number of species by disclosing relevant and identifying characteristics such as structural or other physical and/or chemical properties, by disclosing functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the invention as claimed. See Eli Lilly,119 F.3d at 1568, 43 USPQ2d at 1406.
Applicant’s disclosure is as follows.
Applicant describes identifying V06 resistance gene (SEQ ID NOs: 1-3), in a resistance in Lactuca sativa (lettuce) plant under the seed deposit number NCIMB 43827, (see page 13 lines 3-5). Furthermore, said resistance and unaffected seed production was only seen when sequences did not have the marker 3 (SEQ ID NO: 6) and marker 4 (SEQ ID NO: 7), (see page 10 lines 14-17). Lastly, the specification validated that said gene is resistant to Bermia lactucae, specifically races B1: 1-37EU, (see figure 2 and page 13 lines 1-2).
Claims encompass a V06 resistance gene encoding a protein having at least 95% sequence identity to SEQ ID NO: 3 – the specification only describes a single V06 gene from in L. sativa (seed deposit NCIMB 43827).
The claimed invention lacks adequate written description for the following reasons. Claims 1-3, 5, 7-8, 12-16 and 18-20, are directed to downy mildew resistant Lactuca sativa plant comprising a V06 resistance gene encoding a protein having at least 95% sequence identity to SEQ ID NO: 3, wherein said lettuce plant does not comprise SEQ ID NO: 6 and/or SEQ ID NO:7, and wherein said lettuce plant provides an average seed production of at least 5 g of seed per lettuce plant. Additionally, wherein the plant is resistant to B. lactucae, specifically races B1:1-37EU and/or B1:1-9US.
Additionally, the claims encompass an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 3, a coding sequence having at least 95% sequence identity to SEQ ID NO: 2, a genomic sequence having at least 95% sequence identity to SEQ ID NO: 1. Furthermore, the scope of the claims encompasses V06 resistance genes and encoding sequences obtained from sources other than L. sativa so long as they share at least 95% sequence identity to SEQ ID NOs: 1-3.
The only V06 gene disclosed is from L. sativa (seed deposit NCIMB 43827) being SEQ ID NO: 2-3. From the disclosure of SEQ ID NO: 1-3, one skilled in the art cannot predict gene structures that confer functional activity from other sources and their allelic variants. Applicant does not describe common structures or motifs for V06 resistance gene functionality that is shared by L. sativa (seed deposit NCIMB 43827) plants and other lettuce plants having the same resistance.
The specification describes that SEQ ID NOs: 1-3 was isolated solely from a specific wild-type L. sativa and that is not found in other wild-type sources. The specification does not describe that these sequences are representative of other V06 sequences from other wild-type sources. Moreover, the claimed L. sativa V06 gene (SEQ ID NOs: 1-3), exist exclusively in deposit accession number NCIMB 43827 and is absent from other sources or known wild-types. This required resistance is unique to this single plant having deposit accession number NCIMB 43827.
The specification fails to describe that variants with at least 95% sequence identity will behave conferring resistance against B. lactucae across different lettuce lines, crosses, or wild-types rendering it unknown if the variants will retain functional activity and confer resistance to the claimed races.
The resistance observed is tied to this singular, isolated genetic material. The issue is that the functional activity of variants of SEQ ID NO: 1-3 (i.e., sequences with as little as 95% identity to SEQ ID NO: 1-3) are not predictable because the specification does not describe functional domains or motifs such that one would have no idea if the variants possess the necessary structures to be functionally active and confer resistance.
Furthermore, claims 1-3, 5, 7-8, 12-16 and 18-20 encompass a nucleic acid sequence having at least 95% identity to SEQ ID NO: 1, or encoding a V06 polypeptide with at least 95% identity to SEQ ID NO: 3. This requires the specification to describe nucleic acid sequences encoding such polypeptides.
However, the specification does not describe a nucleic acid sequence having at least 95% identity to SEQ ID NO: 1, or a polynucleotide encoding a V06 polypeptide with at least 95% identity to SEQ ID NO: 3, which leads to a functional V06 polypeptide.
A nucleic acid sequence having at least 95% identity to SEQ ID NO: 1 would have 272 nucleic acid substitutions relative to SEQ ID NO:1, while a polynucleotide encoding a polypeptide with at least 95% identity to SEQ ID NO: 3 would have 70 amino acid substitutions relative to SEQ ID NO: 3.
These polynucleotide and polypeptides would encompass 3272 and 1970 distinct gene and protein variants, respectively. In the absence of describing where in the sequence of SEQ ID NO: 1 such variations can be sustained, one of skill in the art would not be led to believe that Applicant possesses this vast genus of nucleic and amino acid sequences that retain functional activity , or to the make the polypeptide which would retain the activity of SEQ ID NO: 3, and lead to resistance to B. lactucae
Therefore, while the examples describe that certain specific V06 SEQ ID NOs: 1-3 can confer resistance with lettuce, the specification fails to provide adequate description on the motifs, catalytic domains, etc. in these sequences that confers the specifically claimed function of resistance. Applicant has shown one structure/sequence which is not deemed to be a representative number of structures/sequences from the genus of sequences having 95% sequence identity to SEQ ID NO: 1-3 that retain function and thus confer resistance.
For example, a blast search of the top ten results shows proteins as unnamed, predicted, and hypothetical genes.
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(1) here are the alignments none of which have high sequence similarity (2) these search results do not describe structures that confer functionality. Therefore, based on the state of the art the skilled artisan would not know the structures found within sequence having as little as 95% sequence identity to SEQ ID NO: 1-3 that confer resistance to the claimed races.
The lack of a description of a representative number of structures/sequences, the absence of information in the art on conserved regions required for activity, or the impact of 5% variation of the sequence, one skilled in the art would not know the structures conferring claimed resistance. The examples are specific examples tied to a specific starting material, and not reasonably reproducible description to predictably produce downy mildew resistant lettuce plants.
The claims encompass Lactuca sativa plant having any V06 resistance gene with at least 95% sequence identity to SEQ ID NO: 3 – the specification only describes silencing the V06 resistance gene in L. sativa already having resistance and not actually transiently expressed a heterologous gene in another lettuce species.
The claimed invention lacks adequate written description with regard to the genus of plants that comprise V06 resistance gene whereby the plant confers resistance to downy mildew races B1:1-37EU and/or B1:1-9US. The scope of the claims any species of lettuce plant. However, Applicant’s working example is only on silencing the V06 (SEQ ID NO: 1-3) in L. sativa (seed deposit NCIMB 43827), a plant that inherently comprises the V06 resistance gene which results in conferring resistance to downy mildew. Applicant has not shown transiently expressing SEQ ID NOs: 1-3 into another lettuce species and conferring said phenotype.
For example, Xiong et al (The genome of Lactuca saligna, a wild relative of lettuce, provides insight into non-host resistance to the downy mildew Bremia lactucae. 2023. Plant J, 115: 108-126. (previously cited)), describes that using Pfam models PF00931.23 (Nucleotide-binding (NB) domain) and PF01582.20 (Toll/Interleukin-1 Receptor (TIR) domain) to identify for nucleotide-binding leucine-rich repeat (NLR) in lettuce (see page 120 right column last paragraph), which are the same Pfam identifiers that were used to identify Applicants resistance gene (see UniProt alignment above), suggesting that both Xiong’s protein (A0AAU9MS05_9ASTR) and the Applicants V06 resistance protein are the same gene. Moreover, Applicant describes that the V06 resistance gene comprises both the NB and TIR domain (see page 3 lines 3-11).
Xiong further describes that “L. saligna is crossable with L. sativa, the F1 plants are nearly sterile, and the resulting inbred offspring (F2 generation) show severely reduced fertility and transmission ratio distortion (TRD) due to hybrid incompatibility (HI)”, (see page 109 left column middle paragraph), and “If the HI/TRD locus indeed resides in the inversion, then further fine-mapping and introgression of loci associated with HI, and potential immune genes underlying NHR for that matter, will not be feasible due to the lack of recombination caused by inversion.” (see page 117 right column middle paragraph last sentence and figure 3).
Xiong also describes that “the inversion on chromosome 8 co-segregated with an HI region” (see page 117 right column middle paragraph last sentence and figure 3), suggesting that hybrid incompatibility mainly occurs in chromosome 8. Overall, Xiong describes that not all crosses will result in a successfully transfer desired resistance NLR genes (i.e. V06 resistance gene) and phenotype.
Xiong’s description also suggest that not all plants are compatible for crossing. Specifically, because the Applicant’s resistance gene is found on chromosome 8 (see page 8 line 21), and producing at least 5 grams of seed can be hindered by HI. Additionally, Applicant has described that SEQ ID NOs: 6 and 7 are required to see seed yield unaffected.
However, Applicant has not described if HI would successfully omit SEQ ID NOs:6 and 7 to see the same function. Therefore, and in light of the state of the art, the skilled artisan would not be of the opinion that Applicant was in possession of the claimed methods as viable seed is not produced.
Accordingly, there is lack of adequate description to inform a skilled artisan that Applicant was in possession of the claimed invention at the time of filing. See Written Description guidelines published in Federal Register/ Vol.66, No. 4/ Friday, January 5, 2001/ Notices; p. 1099-1111.
Response to Arguments
Applicant's arguments filed 04/23/2026 have been fully considered but they are not persuasive, it is noted that the features upon which applicant relies (i.e., A skilled person in the art would understand from the description of the V06 resistance gene as an NBS-LRR gene that there are certain domains of NBS-LRR proteins that contribute to conferring pathogen resistance to a plant) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In this case the claims do not reflect the claimed description and the specification does not provide enough description on sequence with at least 95% sequence identity to SEQ ID NO: 3. Thus, Applicant’s arguments are not commensurate in scope with what is claimed, and the specification fails to adequately describe possession of the invention as broadly claimed.
Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 112(a)(Enablement)
Claims 1-3, 5, 7-8, 12-16 and 18-20 REMAIN 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 the lettuce plant deposited under NCIMB 43827, does not reasonably provide enablement for any species of lettuce plant comprising a protein having as little as 95% sequence identity to SEQ ID NO: 3 or a coding sequence having as little as 95% sequence identity to SEQ ID NO: 2 or a genomic sequence having as little as 95% sequence identity to SEQ ID NO:1, or methods of using said protein. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
“The first paragraph of 35 U.S.C. § 112 requires, inter alia, that the specification of a patent enable any person skilled in the art to which it pertains to make and use the claimed invention. Although the statute does not say so, enablement requires that the specification teach those in the art to make and use the invention without ‘undue experimentation.’ In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
That some experimentation may be required is not fatal; the issue is whether the amount of experimentation required is ‘undue.’” In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (emphasis in original); see also In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993) (“[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’”) “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” Wands, supra.
Some experimentation, even a considerable amount, is not “undue” if, e.g., it is merely routine, or if the specification provides a reasonable amount of guidance as to the direction in which the experimentation should proceed. Factors to consider include “(1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.” Id.
Applicant’s disclosure is as set forth above. The claimed invention is not enabled for the following reasons. To comply with 35 USC 112(a) enablement, one skilled in the art must be able to make and use the claimed invention.
(A) The breadth of the claims
The breadth of the claims encompasses a L. sativa plant comprising V06 resistance gene having any structure within 95% sequence identity to SEQ ID NOs: 1-3 providing resistance against Bremia lactucae races B1:1-37EU and/or B1:1-9US, wherein said lettuce plant does not comprise SEQ ID NO: 6 and/or SEQ ID NO:7, and wherein said lettuce plant provides an average seed production of at least 5 g of seed per lettuce plant. However, the specification has only taught silencing said gene in L. sativa (seed deposit NCIMB 43827) already comprising downy mildew resistance to B1:1-37EU and/or B1:1-9US and SEQ ID NOs: 1-3.
(B) The nature of the invention.
The nature of the claimed invention is directed to a L. sativa plant comprising the V06 resistance gene having at least 95% sequence identity to SEQ ID NOs: 1-3, whether achieved by hybridization or gene construction, to provide downy mildew resistance. Additionally, wherein said lettuce plant does not comprise SEQ ID NO: 6 and/or SEQ ID NO:7, and wherein said lettuce plant provides an average seed production of at least 5 g of seed per lettuce plant.
(C) The state of the prior art
The art does not teach conserved regions or alignments of said gene. Furthermore, there is a lack of guidance whether V06 resistance gene encoding a protein having at least 95% sequence identity to SEQ ID NO: 3 is found in other lettuce plants.
(E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The claimed invention lacks adequate enabling guidance for the following reasons. Claims 1-3, 5, 7-8, 12-16 and 18-20, are directed to downy mildew resistant Lactuca sativa plant comprising a V06 resistance gene encoding a protein having at least 95% sequence identity to SEQ ID NO: 3, wherein said lettuce plant does not comprise SEQ ID NO: 6 and/or SEQ ID NO: 7, and wherein said lettuce plant provides an average seed production of at least 5 g of seed per lettuce plant. Additionally, wherein the plant is resistant to B. lactucae, specifically races B1:1-37EU and/or B1:1-9US.
Additionally, the claims encompass an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 3, a coding sequence having at least 95% sequence identity to SEQ ID NO: 2, a genomic sequence having at least 95% sequence identity to SEQ ID NO: 1. Furthermore, the scope of the claims encompasses V06 resistance genes and encoding sequences obtained from sources other than L. sativa so long as they share at least 95% sequence identity to SEQ ID NOs: 1-3.
The only V06 resistance gene taught is from L. sativa (seed deposit NCIMB 43827) being SEQ ID NOs: 1-3. From the disclosure of SEQ ID NOs: 1-3, one skilled in the art cannot predict the structures of other V06 genes from other sources and their allelic variants. Applicant does not teach common structures or motifs for V06 resistance genes shared by L. sativa (seed deposit NCIMB 43827) plants or any lettuce plant that would allow one skilled in the art to predict their structures of V06 resistance genes.
The teaching of SEQ ID NOs: 1-3 was isolated solely from a specific wild-type L. sativa deposit and is not found in other wild-type sources, and lacks the presence or absence of working examples and guidance of V06 resistance sequences from other wild-type sources having at least 95% sequence identity. Moreover, the claimed L. sativa V06 resistance gene (SEQ ID NOs: 1-3), exist exclusively under deposit accession numbers NCIMB 43827 and is absent from other sources, crosses, or known wild-types. This required resistance is unique to this single isolate under deposit accession numbers NCIMB 43827.
The specification fails to TEACH, or fails to provide GUIDANCE variants with at least 95% sequence identity will behave predictably across different lettuce lines, crosses, or wild-types. The resistance observed is tied to this singular, isolated genetic material. The lack or guidance and the lack of working examples suggests that other wild-types L. sativa plants or variants would be unpredictable to have the same function or structure.
Furthermore, claims 1-3, 5, 7-8, 12-16 and 18-20 encompass a nucleic acid sequence having at least 95% identity to SEQ ID NO: 1, or encoding a V06 polypeptide having an amino acid sequence with at least 95% identity to SEQ ID NO: 3. This requires the specification to teach nucleic acid sequences encoding such polypeptides.
However, the specification does not teach or provide guidance for making a nucleic acid sequence having at least 95% identity to SEQ ID NO: 1, or a polynucleotide encoding a V06 polypeptide with at least 95% identity to SEQ ID NO: 3, which leads to a functional V06 polypeptide.
A nucleic acid sequence having at least 95% identity to SEQ ID NO: 1 would have 272 nucleic acid substitutions relative to SEQ ID NO:1, while a polynucleotide encoding a polypeptide with at least 95% identity to SEQ ID NO: 3 would have 70 amino acid substitutions relative to SEQ ID NO: 3.
These polynucleotide and polypeptides would encompass 3272 and 1970 distinct gene and protein variants, respectively. In the absence of guidance indicating where in the sequence of SEQ ID NO: 1 such variations can be sustained, undue trial and error experimentation would be required to make the claimed polynucleotides of SEQ ID NO: 1, or to the make the polypeptide which would retain the activity of SEQ ID NO: 3, and lead to resistance to B. lactucae
Therefore, while the examples teach that certain specific V06 SEQ ID NOs: 1-3 can confer resistance with lettuce, the specification fails to teach motifs, catalytic domains, etc. in these sequences that confers the specifically claimed function of resistance. Applicant has not shown one structure/sequence having 95% sequence identity that retain function and thus confer resistance.
For example, a blast search of the top ten results shows proteins as unnamed, predicted, and hypothetical lacking adequate enabling guidance of other V06 resistance genes.
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Therefore, because the art fails to teach the structures required for V06 functional activity, a person skilled in the art would be unable to predictably make, and thus use, the claimed amino and nucleic acid sequences as the specification fails to teach the critical domains and motifs that are required for functional activity.
The lack of representative sequences, information on conserved regions required for activity, or the impact of 5% variation of the sequence, shows there is not enough guidance to predictably make and/or use the claimed sequences. The examples are specific examples tied to a specific starting material, and not reasonably reproducible teachings to predictably produce downy mildew resistant lettuce plants.
The claimed invention lacks adequate enabling guidance with regard to the genus of plants that comprise V06 gene whereby the plant confers resistance to downy mildew races B1:1-37EU and/or B1:1-9US. The scope of the claims encompass a L. sativa plant.
However, Applicant’s working example is only silencing the V06 resistance gene in L. sativa (seed deposit NCIMB 43827), a plant that inherently comprises the V06 resistance gene which results in conferring resistance to downy mildew races B1:1-37EU and/or B1:1-9US. Applicant has not taught transiently expressing SEQ ID NOs: 1-3 into another L. sativa utilizing other V06 gene besides seed deposit NCIMB 43827 and conferring said phenotype.
For example, Xiong et al (The genome of Lactuca saligna, a wild relative of lettuce, provides insight into non-host resistance to the downy mildew Bremia lactucae. 2023. Plant J, 115: 108-126. (previously cited)), teaches that using Pfam models PF00931.23 (Nucleotide-binding (NB) domain) and PF01582.20 (Toll/Interleukin-1 Receptor (TIR) domain) to identify for nucleotide-binding leucine-rich repeat (NLR) in lettuce, (see page 120 right column last paragraph), which are the same Pfam identifiers that were used to identify Applicants resistance gene, (see UniProt alignment above). The Applicant discloses that the V06 resistance gene comprises both the NB and TIR domain, (see page 3 lines 3-11), suggesting that both Xiong’s protein (A0AAU9MS05_9ASTR) and the Applicants V06 resistance protein are the same gene.
Xiong further teaches that “L. saligna is crossable with L. sativa, the F1 plants are nearly sterile, and the resulting inbred offspring (F2 generation) show severely reduced fertility and transmission ratio distortion (TRD) due to hybrid incompatibility (HI)”, (see page 109 left column middle paragraph), and “If the HI/TRD locus indeed resides in the inversion, then further fine-mapping and introgression of loci associated with HI, and potential immune genes underlying NHR for that matter, will not be feasible due to the lack of recombination caused by inversion.” (see page 117 right column middle paragraph last sentence and figure 3). Lastly, Xiong teaches that “the inversion on chromosome 8 co-segregated with an HI region” (see page 117 right column middle paragraph last sentence and figure 3), suggesting that hybrid incompatibility mainly occurs in chromosome 8. Overall, Xiong teaches that not all crosses will result in a successfully transfer desired resistance NLR genes (i.e. V06 resistance gene) and phenotype.
Xiong teaching also suggest that not all plants are compatible for crossing. Specifically, because the Applicant’s resistance gene is found on chromosome 8, (see page 8 line 21), and producing at least 5 grams of seed can be hindered by HI. Additionally, Applicant has taught that SEQ ID NOs: 6 and 7 are required to see seed yield unaffected. However, Applicant has not taught if HI would successfully omit SEQ ID NOs:6 and 7 to see the same function. Therefore, it would be unpredictable for one skilled in the art to successfully produce a lettuce plant with the specific phenotype.
Neither the Applicant nor the prior art teach that the V06 resistance gene successfully confer said phenotype in other lettuce species other than L. sativa (seed deposit NCIMB 43827). Furthermore, the Applicant failed to teach adequate guidance within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus having said phenotype.
Given the breadth of the claims, the lack of sufficient guidance, the absence of working examples regarding the structure of V06 having at least 95% sequence identity to SEQ ID NOs:1-3 which confer functional activity, the state of the prior art, and unpredictability in the art, one skilled in the art cannot make and use the claimed invention as commensurate in scope with the claims without excessive burden and undue experimentation.
For at least this reason, the Specification does not teach a person with skill in the art how to make and/or use the subject matter within the full scope of these Claims.
Response to Arguments
Applicant's arguments filed 04/23/2026 have been fully considered but they are not persuasive. While Applicants argument rely on that “Without conceding the Office's position, solely to advance prosecution, Applicant submits that the present claims do not recite the 90% sequence variability language, rendering this rejection moot”, however the specification does not enable sequences having at least 95% sequence identity to SEQ ID NO: 3 and conferring said phenotype. Thus, Applicant’s arguments are not commensurate in scope with what is claimed, and the specification fails to adequately enable sequences with at least 95% sequence identity and provide enough working examples of the invention as broadly claimed.
Therefore, the rejection is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/C.J.O./Examiner, Art Unit 1663
/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662
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