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 amendments of claims 1, 5, 11 and 14 in the reply filed on 06/05/2026 is acknowledged.
Claims 1, 3, 5, 8-11, 14 and 17-18 are pending and the claims along with Applicant’s elected species of SEQ ID NO: 4 are examined in this office action.
Rejections that are withdrawn
Rejection to specification is withdrawn in light of applicant’s amendment of specification by including a proper symbol indicating use in commerce.
35 USC § 112 written description requirements rejection has been withdrawn in light of applicant’s amendment of claims 1, 5, 11 and 14 by deleting “95% sequence identity” and by including specific pest species of “fall armyworm (Spodoptera frugiperda), corn earworm (Helicoverpa zea), sugarcane borer (Diatraea saccharalis), western corn rootworm (Diabrotica virgifera virgifera), or combinations thereof”.
Following improper Markush grouping rejection has been modified in light of applicant’s amendments of claims 1, 5, 11 and 14 by deleting “95% sequence identity” and by narrowing down number of sequences, see analysis below.
Improper Markush Groups
Claims 1, 3, 5, 8-11, 14 and 17-18 are rejected under the judicially-created basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-722 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. and Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or common use that flows from the substantial structural feature and/or common use that flows from the substantial structural feature for the following reasons:
Claims 1, 5, 11 and 14 recite transformed plant or host cell comprising a recombinant nucleic acid molecule encoding a pesticidal polypeptide of SEQ ID NOs: 3, 4, 6, 14, 21, 32, 62, 74, 86-88, 90-93, 95, 96, 98, 100, 102, 107, 108, 110, 112-119, 121, 122, 124-144, 146, 147, 149, 151-159, 162, or 166. Specification provides the description of the sequence in Tables 1-4, and it is clear there are numerous different proteins that do not appear to be from the same family of proteins, and therefore they do not have the same function for example Tables 1-4 showed that they have different insecticidal activity to insects corn earworm (CEW), European corn borer (ECB) and Fall army worm (FAW). There are some engineered variants among the sequences to have no insecticidal activity or are not tested for insecticidal activity for either CEW, ECB or FAW or other insects. Therefore, they constitute proteins that does not have common use as have insecticidal activity against the common insects. Furthermore, sequence alignment in Figures 3A and 3B showed the polypeptides has various identity to each other ranging from about 59%-99%. This shows that the recited proteins of SEQ ID NOs: 3, 4, 6, 14, 21, 32, 62, 74, 86-88, 90-93, 95, 96, 98, 100, 102, 107, 108, 110, 112-119, 121, 122, 124-144, 146, 147, 149, 151-159, 162, or 166 do not share a substantial feature and/or common use that flows from the substantial structural feature and/or common use that flows from the substantial structural feature.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or groupings of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 USC 134 and 37 CFR 41.31 (a)(1).
Following 35 USC § 112 scope of enablement rejection has been modified in light of applicant’s amendment of claims 1, 5, 11 and 14 by deleting “95% sequence identity” and by including specific pest species of “fall armyworm (Spodoptera frugiperda), corn earworm (Helicoverpa zea), sugarcane borer (Diatraea saccharalis), western corn rootworm (Diabrotica virgifera virgifera), or combinations thereof”.
Response to Arguments
Applicant's arguments filed 06/05/2026 have been fully considered but they are not persuasive.
Applicant argues Markush grouping is improper only where the claimed alternatives do not share both a substantial structural feature and a common use that flows from that feature. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980); MPEP § 2117. Applicant argues every alternative encompassed by the amended claims shares a conserved monalysin-like protein structure tied to a common use of specific insecticidal activity. Applicant argues instant specification at Example 1 explains that the disclosed base sequence of SEQ ID NO: 1 is a sequence from Myxococcus fulvus and that "strategic engineering methods were used to create novel insecticidal engineered variants (SEQ ID NO: 2-184)”. Applicant argues the claimed sequences are not an arbitrary collection of unrelated proteins, but rather a family of engineered variants derived from a common starting sequence (Response to rejection, page 7 and 8 , last and first paragraph).
Applicant argues the recited functional elements in amended claims 1, 5, 11, and 14 require pesticidal activity against plant pests comprising fall armyworm (Spodoptera frugiperda), corn earworm (Helicoverpa zea), sugarcane borer (Diatraea saccharalis), western corn rootworm (Diabrotica virgifera virgifera), or combinations thereof. Applicant argues polypeptide sequence list recited in the amended claims is drawn from that experimentally characterized subgroup rather than the full original genus. Applicant argues variations in activity spectrum across different pest species are expected in insecticidal protein engineering and thus do not negate the common use. Applicant argues the Markush grouping standard requires a "common use," not an identical activity profile. Applicant argues this common use of insecticidal activity flows directly from the shared structural features, as the conserved monalysin-like pore-forming architecture forms the structural basis for insecticidal activity against the claimed pests. Applicant argues the amended claims now recite a common use that is not generic activity against any plant pest, but instead a common pesticidal use directed to a defined set of insect pests (page 8, paragraph 2).
Applicant's arguments have been fully considered but they are not persuasive since Applicant has not described a common structure or domain or motifs that are conserved in these diverse sequences in their variants forms recited in claims 1, 5, 11 and 14, to make them the same pore forming toxin groups since for example SEQ ID NOs:4 and 166 has only 86% identity, see alignment below. The bioassay results of table 1showed the SEQ ID NO:166 has insecticidal property to SCB and WCR wherein SEQ ID NO:4 does not have any insecticidal activities, therefore the sequences SEQ ID NOs: 3, 4, 6, 14, 21, 32, 62, 74, 86-88, 90-93, 95, 96, 98, 100, 102, 107, 108, 110, 112-119, 121, 122, 124-144, 146, 147, 149, 151-159, 162, or 166 are not alternatively useable members. MPEP § 2111 states “A Markush grouping is proper if the members of a group share a single structural similarity and a common use.” And “A Markush claim may be rejected under judicially approved “improper Markush grouping” principles when the claim contains an improper grouping of alternatively useable members”. The alternatives should (1) share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class, and (2) share a common function or use when they are disclosed in the specification or known in the art to be functionally equivalent in the context of the claimed invention. A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
Applicant has not described that these diverse sequences have a “single structural similarity” (i.e. some of them have low sequence identity) and a common use (i.e. they react to different species of insects). The mutation i.e. insertions, deletions and substitution would lead to diverse proteins.
Query: unnamed protein product Query ID: lcl|Query_541783 Length: 261
>unnamed protein product
Sequence ID: Query_541785 Length: 261
Range 1: 1 to 261
Score:459 bits(1181), Expect:1e-170,
Method:Compositional matrix adjust.,
Identities:224/261(86%), Positives:243/261(93%), Gaps:0/261(0%)
Query 1 MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV 60
M ++ ++++L+M+ L++++ LSQIPPESYRTKSPAELLGAGKTRADLNFPDV
Sbjct 1 MQQDTNGRETTLKMDGLDRDRAGGANAGLSQIPPESYRTKSPAELLGAGKTRADLNFPDV 60
Query 61 KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG 120
KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG
Sbjct 61 KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG 120
Query 121 TSIEHTLTKKKGFTSRFTASTEVKVGASAGVFACETSLEVTTGFSYGQDINEETTETWKK 180
TSIE++LTKKKGF+ +FTASTEVKVG SAG+F CETSLEVTTGFSY + INEETTETWKK
Sbjct 121 TSIEYSLTKKKGFSRQFTASTEVKVGVSAGIFGCETSLEVTTGFSYSETINEETTETWKK 180
Query 181 TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD 240
T+ GPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD
Sbjct 181 TLTGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD 240
Query 241 IGYLSLQTVIEYMCNEAWSRW 261
IGYLSLQTVIEYMCNEAWSRW
Sbjct 241 IGYLSLQTVIEYMCNEAWSRW 261
Claim Rejections - 35 USC § 112 – Scope of Enablement
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, 5, 8-11, 14 and 17-18 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 transformed plant, seed, or plant part comprising a recombinant nucleic acid molecule encoding a polypeptide SEQ ID NO: 4 operably linked to heterologous promoter operably linked to the recombinant nucleic acid and plant or plant cell comprising the construct or a vector, does not reasonably provide enablement for a recombinant polynucleotide encoding the polypeptide, comprising an amino acid sequence of SEQ ID NO: 4, a vector comprising the polynucleotide and a transformed host cell comprising the polynucleotide would have any level of pesticidal activity against plant pest comprising fall armyworm (Spodoptera frugiperda), corn earworm (Helicoverpa zea), sugarcane borer (Diatraea saccharalis), western corn rootworm (Diabrotica virgifera virgifera), or combinations thereof. 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.
An “analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.” MPEP 2164.01. “A conclusion of lack of enablement means that. the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention [i.e. commensurate scope] without undue experimentation.” In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); MPEP 2164.01.
In In re Wands, 858 F.2d 731,8 USPQ2d 1400 (Fed. Cir. 1988), several factors implicated in determination of whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” are identified. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). No single factor is independently determinative of enablement; rather “[i]t is improper to conclude that a disclosure is not enabling based on an analysis of only one of the above factors while ignoring one or more of the others.” MPEP 2164.01. Likewise, all factors may not be relevant to the enablement analysis of any individual claim.
The Breadth of the Claims and nature of invention:
1, 5, 11 and 14 recite SEQ ID NO: 4 has activity against plant pests comprising fall armyworm (Spodoptera frugiperda), corn earworm (Helicoverpa zea), sugarcane borer (Diatraea saccharalis), western corn rootworm (Diabrotica virgifera virgifera), or combinations thereof.
The state of the prior art:
Sequence from Myxococcus fulvus (GUN2873.1.2; SEQ ID NO: 1) (page 33, paragraph 000114) was engineered to create novel insecticidal engineered variants (SEQ IDNO: 2-184) with increased insecticidal activity, altered spectrum of insecticidal activity, or increased stability) (page 33, paragraph 000114). Alignment of SEQ ID NO: 1 to the NCBI protein database showed the sequence from "Myxococcus fulvus" strain "DSM 16525" from accession FOIB01000002.1 has 100% sequence identity to SEQ ID NO: 1 (see enclosed PDF) which has a region (see description in “region 58…257) a pore-forming module of Pseudomonas entomophila monalysin and similar aerolysin type beta barrel.
Furthermore, Selvapandiyan et al. (Published: 2001, Journal: Applied and Environmental Microbiology, 67(12), 5855-5858) teaches deletion of 39 amino acid from N-terminus and 154 amino acids from C-terminus differentially effected the toxicity against larvae of different species of insects suggesting different mechanism of toxicity happens in different size of toxic fragment (Selvapandiyan, page 5858, left paragraph 2, and Table 3). Selvapandiyan further teaches no toxic activity was observed with 220 amino acid deletion from C-terminal of the insecticidal VIP protein (Selvapandiyan, page 5858, left paragraph 2, and Table 3) showing the toxin fragment required to be of certain size to be active. In contrast, applicant does not describe toxin fragment of SEQ ID NO: 4 would have any toxicity.
Leone et al. (Published: 2015, Journal: The journal of biological chemistry 290 (21): 13191–13201) teaches recognition and binding to a specific receptor is required to cause Pore-forming toxins (PFTs) to associated with the target membrane, form multimers, and undergo a conformational change, leading to the formation of an aqueous pore inserted in the membrane (page 13191, right paragraph 1).
Han et al. (Published:04/ 2024, Journal: Front. Microbiol. 15:1378288. doi: 10.3389/fmicb.2024.1378288) teaches a strain M. fulvus strain WCHO5 has been used for biocontrol agent for example for fire blight disease (page 1, Abstract), there is no indication that the recited pore forming protein has been important for the control of fire blight pathogen or any plant pest.
Furthermore, Wei et al. (Published: 2018, Journal: Plant Biotechnology Journal 16: 649–659) teaches their disclosed insecticidal protein is selective protein with highly specific to certain coleopteran insect species, especially to the members of the corn rootworm complex and it is not active against the spotted lady beetle and various lepidopteran and hemipteran insect species wherein the protein does not have shared motifs, domains or signatures to other known proteinaceous toxins (page 655, left last paragraph).
A database search of SEQ ID NO:4 to the GenEmbl database showed it has 96% identity to A0A511SVI2_MYXFU from Myxococcus fulvus (see alignment above) with no indication that the sequence would have been useful for pesticidal protein for any pest.
RESULT 1
A0A511SVI2_MYXFU
ID A0A511SVI2_MYXFU Unreviewed; 261 AA.
AC A0A511SVI2;
DT 13-NOV-2019, integrated into UniProtKB/TrEMBL.
DT 13-NOV-2019, sequence version 1.
DT 28-JAN-2026, entry version 11.
DE RecName: Full=Monalysin Pore-forming domain-containing protein {ECO:0000259|Pfam:PF18063};
GN ORFNames=MFU01_09370 {ECO:0000313|EMBL:GEN05900.1},
GN SAMN05443572_102981 {ECO:0000313|EMBL:SET64083.1};
OS Myxococcus fulvus.
OC Bacteria; Pseudomonadati; Myxococcota; Myxococcia; Myxococcales;
OC Cystobacterineae; Myxococcaceae; Myxococcus.
OX NCBI_TaxID=33 {ECO:0000313|EMBL:GEN05900.1, ECO:0000313|Proteomes:UP000321514};
RN [1] {ECO:0000313|EMBL:SET64083.1, ECO:0000313|Proteomes:UP000183760}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 16525 {ECO:0000313|EMBL:SET64083.1,
RC ECO:0000313|Proteomes:UP000183760};
RA Varghese N., Submissions S.;
RL Submitted (OCT-2016) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|EMBL:GEN05900.1, ECO:0000313|Proteomes:UP000321514}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NBRC 100333 {ECO:0000313|EMBL:GEN05900.1,
RC ECO:0000313|Proteomes:UP000321514};
RA Hosoyama A., Uohara A., Ohji S., Ichikawa N.;
RT "Whole genome shotgun sequence of Myxococcus fulvus NBRC 100333.";
RL Submitted (JUL-2019) 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:GEN05900.1}.
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DR EMBL; BJXR01000013; GEN05900.1; -; Genomic_DNA.
DR EMBL; FOIB01000002; SET64083.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A511SVI2; -.
DR Proteomes; UP000183760; Unassembled WGS sequence.
DR Proteomes; UP000321514; Unassembled WGS sequence.
DR CDD; cd17904; PFM_monalysin-like; 1.
DR InterPro; IPR040927; PF_Monalysin.
DR InterPro; IPR038768; SmlA.
DR PANTHER; PTHR35884:SF1; MONALYSIN BETA BARREL PORE-FORMING DOMAIN-CONTAINING PROTEIN-RELATED; 1.
DR PANTHER; PTHR35884; SMALL AGGREGATE FORMATION PROTEIN; 1.
DR Pfam; PF18063; BB_PF; 1.
PE 4: Predicted;
KW Reference proteome {ECO:0000313|Proteomes:UP000183760}.
FT DOMAIN 60..255
FT /note="Monalysin Pore-forming"
FT /evidence="ECO:0000259|Pfam:PF18063"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 261 AA; 29089 MW; ECA8DD3E303A6669 CRC64;
Query Match 96.0%; Score 1334; Length 261;
Best Local Similarity 95.0%;
Matches 248; Conservative 7; Mismatches 6; Indels 0; Gaps 0;
Qy 1 MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV 60
Qy 61 KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG 120
Qy 121 TSIEHTLTKKKGFTSRFTASTEVKVGASAGVFACETSLEVTTGFSYGQDINEETTETWKK 180
||||::|||||||: :|||||||||| |||:| ||||||||||||| : |||||||||||
Db 121 TSIEYSLTKKKGFSRQFTASTEVKVGVSAGIFGCETSLEVTTGFSYSETINEETTETWKK 180
Qy 181 TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD 240
|: |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TLTGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD 240
Qy 241 IGYLSLQTVIEYMCNEAWSRW 261
|||||||||||||||||||||
Db 241 IGYLSLQTVIEYMCNEAWSRW 261
Spec, Table 1 showed many sequences for example SEQ ID NO: 7 which has 97% sequence identity (see alignment below) and SEQ ID NO: 2 has 98% identity and SEQ ID NO: 5 has 99% to SEQ ID NO:4 that has no effect on activity any of the insect tested in the Bioassay. Furthermore, there are many more sequences within recited identity range that does not show any effect to the tested sample of insects or some sequence only has effect to one or two of the insects tested.
Alignment of SEQ ID NOs: 4 and 2.
Query: unnamed protein product Query ID: lcl|Query_2761703 Length: 261
>unnamed protein product
Sequence ID: Query_2761705 Length: 261
Range 1: 1 to 261
Score:530 bits(1365), Expect:0.0,
Method:Compositional matrix adjust.,
Identities:255/261(98%), Positives:257/261(98%), Gaps:0/261(0%)
Query 1 MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV 60
MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV
Sbjct 1 MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV 60
Query 61 KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG 120
KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG
Sbjct 61 KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG 120
Query 121 TSIEHTLTKKKGFTSRFTASTEVKVGASAGVFACETSLEVTTGFSYGQDINEETTETWKK 180
TSIEHTLTKKKGFTSRFTASTEVKVG SAG+F CETSLEVTTGFSY + INEETTETWKK
Sbjct 121 TSIEHTLTKKKGFTSRFTASTEVKVGVSAGIFGCETSLEVTTGFSYSETINEETTETWKK 180
Query 181 TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD 240
TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD
Sbjct 181 TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD 240
Query 241 IGYLSLQTVIEYMCNEAWSRW 261
IGYLSLQTVIEYMCNEAWSRW
Sbjct 241 IGYLSLQTVIEYMCNEAWSRW 261
Alignment of SEQ ID NOs: 4 and 7.
Query: unnamed protein product Query ID: lcl|Query_3003783 Length: 261
>unnamed protein product
Sequence ID: Query_3003785 Length: 261
Range 1: 1 to 261
Score:528 bits(1360), Expect:0.0,
Method:Compositional matrix adjust.,
Identities:254/261(97%), Positives:255/261(97%), Gaps:0/261(0%)
Query 1 MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV 60
MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV
Sbjct 1 MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV 60
Query 61 KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG 120
KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDT+PSG
Sbjct 61 KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTIPSG 120
Query 121 TSIEHTLTKKKGFTSRFTASTEVKVGASAGVFACETSLEVTTGFSYGQDINEETTETWKK 180
TS EHTLTKKKGFTSRFT S EVK GASAGVFACE SLEVTTGFSYGQDINEET ETWKK
Sbjct 121 TSEEHTLTKKKGFTSRFTVSAEVKAGASAGVFACEASLEVTTGFSYGQDINEETEETWKK 180
Query 181 TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD 240
TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD
Sbjct 181 TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD 240
Query 241 IGYLSLQTVIEYMCNEAWSRW 261
IGYLSLQTVIEYMCNEAWSRW
Sbjct 241 IGYLSLQTVIEYMCNEAWSRW 261
Alignment of SEQ ID NOs: 4 and 5.
Query: unnamed protein product Query ID: lcl|Query_2905031 Length: 261
>unnamed protein product
Sequence ID: Query_2905033 Length: 261
Range 1: 1 to 261
Score:537 bits(1383), Expect:0.0,
Method:Compositional matrix adjust.,
Identities:259/261(99%), Positives:259/261(99%), Gaps:0/261(0%)
Query 1 MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV 60
MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV
Sbjct 1 MNNESQAKDSSLRMEPLEKEKGAAGQGALSQIPPESYRTKSPAELLGAGKTRADLNFPDV 60
Query 61 KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG 120
KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG
Sbjct 61 KNDYELDNALIGQTVTSNGCVVKAPWVRKDFNTPGYWSEGYIKPCAAYLSYIKKDTVPSG 120
Query 121 TSIEHTLTKKKGFTSRFTASTEVKVGASAGVFACETSLEVTTGFSYGQDINEETTETWKK 180
TSIEHTLTKKKGFTSRFTAS EVKVGASAGVFACE SLEVTTGFSYGQDINEETTETWKK
Sbjct 121 TSIEHTLTKKKGFTSRFTASAEVKVGASAGVFACEASLEVTTGFSYGQDINEETTETWKK 180
Query 181 TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD 240
TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD
Sbjct 181 TVAGPQDYWTFQPVLLYAWKVNANALSYMSPKPSLYYTSGKTTYIFSPVFRNSPSTIDKD 240
Query 241 IGYLSLQTVIEYMCNEAWSRW 261
IGYLSLQTVIEYMCNEAWSRW
Sbjct 241 IGYLSLQTVIEYMCNEAWSRW 261
The amount of direction provided by the inventor:
Sequence from Myxococcus fulvus (GUN2873.1.2; SEQ ID NO: 1) was found to have insecticidal activity against corn rootworm, Diabrotica virgifera (CRW) (page 33, paragraph 000114).
Further strategic engineering methods were used to create novel insecticidal engineered variants (SEQ ID NO: 2-184) with increased insecticidal activity, altered spectrum of insecticidal activity, or increased stability) (page 33, paragraph 000114).
Insecticidal toxicity bioassays were conducted with transformed bacterial E. coli whole cells expressing proteins to evaluate pesticidal efficacy against pests including armyworms, Spodoptera spp., corn earworm, Helicoverpa spp., corn borer, Ostrinia spp., Diatraea spp., Anticarsia spp., and Diabrotica spp. (page 34, paragraph 000116).
Measured insecticidal activity of whole recombinant E. coli culture expressing insecticidal proteins of Table 1 showed SEQ ID NO:4 has no insecticidal activity for any of the tested insects of FAW, CEW, SCB and WCR (page 34).
Spec, page 34-39, Table 1 showed many sequences for example SEQ ID NO: 7 which has 97% sequence identity (see alignment below) and SEQ ID NO: 2 has 98% identity and SEQ ID NO: 5 has 99% to the SEQ ID NO:4 that have no effect on activity any of the insect pest tested in the Bioassay. Furthermore, there are many more sequences within recited identity range that does not show any effect to the tested sample of insects or some sequence only has effect to one or two of the insects tested.
The existence of working examples:
The Specification or state of the art 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 because:
Applicant does not teach a polypeptide having at least 95% sequence identity to SEQ ID NO: 4 would have pesticidal activity against any plant pest (claims 1, 5, 11 and 14).
Applicant does not teach the SEQ ID NO: 4 would have activity against a large number of plant pest comprising fall armyworm (Spodoptera frugiperda), corn earworm (Helicoverpa zea), sugarcane borer (Diatraea saccharalis), western corn rootworm (Diabrotica virgifera virgifera), or combinations thereof.
Lack of a working example is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP § 2164.
Genetech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
In the absence of guidance from either the instant disclosure or the art, it would require undue trial and error experimentation for a skilled artisan to make and use the broadly claimed polynucleotide and polypeptides, with no reasonable expectation of success in arriving at a protein of SEQ ID NO:4 having pesticidal activity against a of plant pest comprising fall armyworm (Spodoptera frugiperda), corn earworm (Helicoverpa zea), sugarcane borer (Diatraea saccharalis), western corn rootworm (Diabrotica virgifera virgifera), or combinations thereof.
Thus, in view of the unpredictability associated with effect to different insect species, the lack of enabling guidance from either the instant disclosure or the art, and breath and diversity of the embodiments encompassed by the claimed genus, the lack of sufficient working examples, and the level of the art at the time of the invention, one of ordinary skill in the art must rely on undue trial and error experimentation to make and test the numerous polypeptides encompassed by the broad genera, in order to make and/or use the invention within the full scope of these claims.
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 06/05/2026 have been fully considered but they are not persuasive.
Applicant argues specification expressly states that "While some proteins did not exhibit significant insecticidal activity as tested using this specific diet-overlay bioassay format, other experimental test conditions or bioassays may result in insecticidal activity being measured for those proteins." See Specification at, paragraph [000118]. Applicant argues the absence of activity in one assay format is not equivalent to absence of pesticidal utility under all conditions, particularly where the specification evaluates activity across multiple expression systems and assay formats (Response to rejection, pages 9 and 10, last and first paragraphs).
Applicant argues Regarding enablement rejection, Applicant argues with respect to SEQ ID NO: 4, the absence of activity in a particular E. coli assay does not establish non-enablement. Applicant argue the specification teaches expression of the disclosed polypeptides in multiple systems, including bacterial (E. coli) and plant-based (Agrobacterium-mediated) expression systems, and evaluates pesticidal activity using different assay formats (see, e.g., paragraphs [000115]-[000116]; and Tables 1-2). Applicant argues disclosures demonstrate that pesticidal activity is assessed under differing expression contexts and experimental conditions, rather than a single uniform assay (Response to rejection, pages 10 and 11, last and first paragraphs).
Applicant agues the instant application provides sufficient data and written description support to fully enable the claimed polypeptide sequences of SEQ ID NOs: 3, 4, 6 etc., as well as the claims pest FAW, CEW etc. as recited in amended claims (Response to rejection, page 11, paragraph 2).
Applicant's arguments have been fully considered but they are not persuasive since applicant has not shown any toxicity to any insect caused by the protein of SEQ ID NO:4, wherein the existing arts Leone et al. and Selvapandiyan (see above) are clear the protein would have specific activity which is further showed in Spec, tables 1-4 that some protein for example SEQ ID NO:4 does not have activity against any insect species. Regarding argument on “other experimental test conditions or bioassays may result in insecticidal activity” is moot point since applicant has not described the activity of the protein of SEQ ID NO:4 in any other test conditions or bioassays. Therefore, the rejection has been maintained.
Summary
No claim is allowed.
Claims are free of prior art. The closest prior art is Wei et al. (Published 2018, Journal: Plant Biotechnology Journal 16: 649–659) (previously presented) which teaches the monalysin, a β-pore-forming toxin from P. entomophila, showed lethal effects on insects Drosophila (page 653, right last paragraph). The patentable distinction is that Wei et al. does not teach SEQ ID NO:4 is operably linked to one or more heterologous promoter sequences and the encoded protein has pesticidal activity any pest species (claims 1, 5, 11 and 14) or against a specific plant pest (claims 2, 6, 12 and 15) comprising corn rootworm (Diabrotica virgifera), western corn rootworm (Diabrotica virgifera virgifera), northern corn rootworm (Diabrotica barberi), southern corn rootworm (Diabrotica undecimpunctata howardi) etc.
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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/SANTOSH SHARMA/Examiner, Art Unit 1663
/DAVID H KRUSE/Primary Examiner, Art Unit 1663
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