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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 06/18/2026 has been entered.
Election/Restrictions
Applicant’s amendment of claims 40, 47 and 72 in reply filed on 06/18/2026 has been acknowledged.
Applicants’ election without traverse of species of SEQ ID NO: 139, SEQ ID NO: 145, and SEQ ID NO: 161 in the reply filed on 11/19/2022 is acknowledged.
Claims 40, 42-43, 45-47, 50-51, 53-54, 72-75 and 77-79 are pending and the claims along with the recited species of SEQ ID NOs:10-15 from claims 40, 47 and 72 are examined in this office action.
Following Improper Markush Groups rejection has been maintained since applicant has not specifically recited the group of sequence which share substantial structure feature and a common use that flows from the substantial structural feature.
Improper Markush Groups
Claims 40, 42-43, 45-47, 50-51, 53-54, 72-75 and 77-79 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 47 recite insecticidal polypeptides of SEQ ID NOs: 10-41, 43-45, 235-255, or 258-273 and claims 40 and 72 recite engineered polypeptide of SEQ ID NOs: 10-41. 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 insect 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 6-7 showed the polypeptides has various identity to each other ranging from about 83%-99%. This shows that the recited proteins of SEQ ID NOs: 10-41, 43-45, 235-255, or 258-273 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).
Response to Arguments
Applicants’ arguments filed 06/18/2026 have been fully considered but they are not persuasive.
Applicant argues claims 40, 47, and 72 are amended to recite functional elements related to the common use of insecticidal activity "insecticidal activity against one or more Lepidopteran insect pests selected from fall armyworm (Spodoptera frugiperda), corn earworm (Helicoverpa zea), or European corn borer ( Ostrinia nubilalis)." Wherein claim 40 and 72 does not recite “90% sequence identity”.
Applicants’ arguments have been fully considered but they are not persuasive since Figures 6-7 showed the polypeptides has various identity to each other ranging from about 83%-99%, 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). Thus, the sequences are structurally different, and their uses varies as different insecticidal proteins as shown in Tables 1-4, they does not constitute members of a Markush group. The sequence comprises different origins for example SEQ ID NO:1, SEQ ID NO:3 that has different domains I and II combined with various domain III showing the sequence to not have structural similarity.
Following 35 USC § 112 - written description rejection has been modified in light of applicant’s amendment of claims 40 and 72 to delete the recitation of “90% sequence identity” and recitation of the polypeptides are effective against one or more of Lepidopteran insect pests of fall armyworm (Spodoptera frugiperda), corn earworm (Helicoverpa zea), or European corn borer (Ostrinia nubilalis).
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.
Claim 40, 42-43, 45-47, 50-51, 53-54, 72-75 and 77-79 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 these rejections unless they include a limitation that overcomes the deficiencies of the parent claim.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 40, 47 and 72 recite the broad recitation “corn earworm”, and further limit the scope by the phrase “Helicoverpa zea” in parenthesis (…). There are multiple species of insects they are known as corn earworm. For example Umina et al. (Published: 2015, Accessed in https://cesaraustralia.com/pestnotes/caterpillars/corn-earworm/teaches, accessed on 09/17/2026, Cesar Australia) teaches Helicoverpa armigera is also named as corn earworm (see enclosed PDF).
The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim Rejections - 35 USC § 112 - written description requirements
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 40, 42-43, 45-46, 72-75 and 77-79 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.
Analysis of Breadth of Claims
The domain III region of for example of SEQ ID NOs:10-15 would comprise large genus of sequences in this region since application has not specifically described the domain III region of for example of SEQ ID NOs:10-15.
What is Described in the Specification
Applicant describes:
Engineered polypeptide sequences were designed in silico using a previously identified native Cry89Aa class toxin, originally found in a Bacillus thuringiensis species (PCT/US2022/028078; SEQ ID NO: 1 as disclosed herein) (page 44, paragraph 135).
engineering method altered SEQ ID NO: 1 by exchanging domain III (SEQ ID NO: 151) of SEQ ID NO: 1, a Cry89Aa class native polypeptide (formerly Cry1N class, as disclosed in U.S. Provisional Patent Application No. 63/665,914 and International Patent Application No. PCT/US2025/014957) (page 43, paragraph 135).
SEQ ID NO: 139 is domain I region, SEQ ID NO:145 is the domain II region and SEQ ID NO:161 is the border/linker II region and SEQ ID NO:s:146-151 is domain III region (page 44, paragraph 137).
Engineered Variant 0871.1.1 (SEQ ID NO: 91) was generated using domain swapping techniques between a native Cry1N-like protein (NCBI Accession# WP 170924498 (EntDB 01628); SEQ ID NO: 3) and a native non-Cry1N protein, Cry1Ca5 wherein domain I (SEQ ID NO: 135) and domain II (SEQ ID NO: 141) of the Cry1N were joined to domain III of Cry 1 Ca5 to generate the engineered protein of Engineered Variant 0871.1.1 (SEQ ID NO: 91) (FIG. 4B) (pages 44-45, paragraph 138).
Engineered Variant 00309A (SEQ ID NO:11) comprises domains I (SEQ ID NO: 139) and II (SEQ IDNO: 145) (dld2) from the native Cry89Aa protein AFG02511.1 (SEQ ID NO: 1) from Bacillus thuringiensis (Figure 1) (pages 45, paragraph 139).
Engineered Variant 00309A (SEQ ID NO:11) showed insecticidal activities in Table 1 and Table 3 where Table 3 showed it does not have insecticidal activity against European com borer (ECB).
FIG. 2 and FIG. 5 are example of engineered variants (SEQ ID NOs: 10-39), which showed variation in domain III region and Table 1 showed their different effect to the insects (page 44, paragraph 00136).
Corn plants were stably transformed to express the Engineered Variant Engineered Variant 0309A (SEQ ID NO: 11) insecticidal protein (page 55, paragraph 156).
Difference Between What was Described and What is Claimed
Applicant has not described domain III region of any one of for example SEQ ID NOs: 10-15 (claims 40 and 72) when combined with domain I and II as SEQ ID NOs: 139 and 145 respectively would cause insecticidal property to insect pests of fall armyworm (Spodoptera frugiperda), com earworm (Helicoverpa zea), or European com borer (Ostrinia nubilalis) other than for example SEQ ID NOs: 10-15 themselves.
Applicant has not described a domain III region of for example of SEQ ID NOs:10-15 (claims 40 and 72).
Analysis
The purpose of the written description is to ensure that the inventor had possession at the time the invention was made, of the specific subject claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
Applicant has not expressly described domain III of SEQ ID NOs:10-15 (claims 40 and 72). Applicant describes Engineered Variant 00309A (SEQ ID NO:11) comprises domains I (SEQ ID NO: 139) and II (SEQ ID NO: 145) (d1d2) from the native Cry89Aa protein AFG02511.1 (SEQ ID NO: 1) from Bacillus thuringiensis (Figure 1) (pages 45, paragraph 139).
Applicant describes engineered Variant 0871.1.1 (SEAQ ID NO:91) and Engineered Variant 0309A (SEQ ID NO:11) share a common domain III (that of Cry1Ca5) as showed in common amino acids from 500-655 in Figure 4C wherein the two proteins differ in that Engineered Variant 0871.1.1 comprises domains I (SEQ ID NO: 135) and II (SEQ ID NO: 141) (dld2) from Cry1N (EntDB 01628; SEQ ID NO: 3), whereas Engineered Variant 0309A comprises domains I (SEQ ID NO: 139) and II (SEQ ID NO: 145) (dld2) from the native Cry89Aa protein AFG02511.1 (SEQ ID NO: 1) (page 45, paragraph 000139). Furthermore, table 3 (page 51, paragraph 000147) showed SEQ ID NO:11 has insecticidal activity against CEW, CL, SBL etc. and does not have activity against ECB. There is no data showing that the other engineered variant of SEQ ID NO:91 have any insecticidal activity.
SEQ ID NO: 11 is 643 amino acid (AA), the domain I and II as SEQ ID NOs: 139 and 145 are 257 and 174 AA long respectively. Applicant states the domain III in SEQID NO: 11 is between 500-655 (i.e. which would be 156 AA long), the total would be 587 AA long that would still lack 56 AA long fragment or fragments between the domains. Furthermore, applicant has not described any sequence with only comprising domain I, II and III would have insecticidal activity against fall armyworm (Spodoptera frugiperda), com earworm (Helicoverpa zea), or European com borer (Ostrinia nubilalis) other than SEQ ID NOs: 10-15 themselves, other than the sequence themselves (i.e. SEQ ID NOs:10-15).
Furthermore, the state of the art at the time of the instant invention was that although the skilled artisan would appreciate the engineered protein of SEQ ID NO:10-15, one would not be able to readily predict function of amino acid which has at least SEQ ID NOs: 139, 145 and the domain III from SEQ ID NOs:10-41.For example, Guo et al. (Published Year: 2004, Journal: Proceedings of the National Academy of Sciences, Vol. 101(25), pages: 9205-9210) teaches that while proteins are fairly tolerant to mutations resulting in single amino acid changes, increasing the number of substitutions additively increases the probability that the protein will be inactivated (page 9209, right. col., paragraph 2).
Applicant teaches engineered variant 00309A (SEQ ID NO:11) showed insecticidal activities in Table 1 and Table 3 where Table 3 showed it does not have insecticidal activity against European com borer (ECB). Furthermore, in Spec, Table 1 there are other variants that has no insecticidal activity against ECB and FAW (see Table 1, paragraph 144). Karlova et al. (Published: 2005, Journal of Invertebrate Pathology 88: 169–172) teaches different hybrids with different structures and combinations of domain I, II and III have various toxicity for example hybrid pRK6 (Cry1Ba-Cry1Ac) has showed considerable activity only as a protoxin wherein the lack of trypsin activated toxin of Cry1Ba and its hybrid is due to trypsin processing in domain 1 (page 171, right first paragraph, see other examples in Table 1 below). Furthermore, Sakai et al. (Published: 2007, Journal: Journal of Bioscience and Bioengineering 103(4):381–383 DOI: 10.1263/jbb.103.381) teaches when domain III of Cry1C was replaced with that of Cry1Aa or Cry4A, the hybrid Cry1C protein retained the cytotoxicity showing that domain III of Cry1C is not crucial in determining the cytocidal specificity of Cry1C against Sf9 (page 381, Abstract). Sakai et al. teaches various cytotoxicity in hybrids of different combinations of domains (See Figure 3 below). This showed that any combination of domain I, II and III would not cause the engineered protein to have property of being insecticidal and it would require specific domain combinations. Therefore, there is dearth of description of domain I and domain II amino acid sequence of SEQ ID NO: 1 as SEQ ID NOs: 139 and 145 respectively and the protein comprising the domain III from for example SEQ ID NOs: 10-15 would case insecticidal property. Instead applicant has not described the insecticidal property of any other polypeptide sequence other than for example SEQ ID NOs: 10-15.
Applicant tests many variants in paragraph 147, Table 3 wherein the data showed few variants were effectively insecticidal against many of the tested insects. For example, Bosch et al. (US patent No.: US 6,780,408 Bl, Date of Patent: Aug. 24, 2004) teaches their disclosed proteins each protein has different specificity for example Cry1C is particularly active against S. exigua and M. brassicae (col. 2, lines 1-5). Furthermore, Sakai et al. teaches Cry1C, one of the lepidopteran-specific insecticidal proteins from Bacillus thuringiensis (page 381, Abstract). Therefore, there is dearth of description of any of the domain III from for example SEQ ID NOs: 10-15 would case insecticidal property.
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Applicant has not expressly described any domain III of the polypeptides for example of SEQ ID NOs: 10-15 (claims 40 and 72) that would cause insecticidal property. The domain III region of SEQ ID NO:10-41 would comprise any number of amino acids. Applicant states FIG. 2 and FIG. 5 are example of engineered variants (SEQ ID NOs: 10-39), which showed variation in domain III region and Table 1 showed their different effect to the insects (page 44, paragraph 00136), however it is not clear which region would describe the domain III region for example of SEQ ID NOs: 10-15. For example, Xu et al. teaches there are variations in the domain III regions of for example Cry1A wherein the domain position ranges from 463 to 679 (page 2735, Table 1, see table below). For example, Cry1Ac has large variations in the domain III residues (see figure 4 below). Furthermore, specific residue changes are important to have function of receptor binding, recognition and toxicity (page 2742, first paragraph). Therefore, there is dearth of description of domain III of the sequences for example SEQ ID NO:10-41 when combined with SEQ ID NOs: 139 and 145 as domain I and II would cause insecticidal activity to any insects.
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Given the large structural variable associated with these embodiments, the claims read on an extremely broad and highly diverse structures that would require to have specific function activity against any insects as being insecticidal. Thus, in view of the analysis presented above, a skilled artisan would appreciate that the claims are directed to extremely broad and highly diverge genus of sequence variants that are required to have the specific function activity against any insects as being insecticidal.
Given the large size and structural diversity associated with the claimed genus, Applicant’s disclosure is not representative of the claimed genus as a whole. This point is particularly relevant because, as discussed above, the prior art speaks to the disconnection between the structure of the broadly claimed variants in any plants and the recited specific function.
The test for sufficiency is whether the disclosure of the application relied upon reasonably conveys to one skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Pharm, Inc, v EH Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Lockwood v. Amer. Airlines, ina, 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). "An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations. Lockwood, 107 F.3d at 1572, 41 USPG2d at 1966". While the written description requirement does not demand either examples or an actual reduction, actual "possession" or reduction to practice outside of the specification is not enough. Ariad Pharm, Inc. v. Eli Lilly & Co., 598 F,3d 1336,1352 (Fed. Cir. 2010). Rather, it is the specification itself that must demonstrate possession. Id.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. The court stated that, “A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNAs, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F. 3d 1559; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
Thus, based on the analysis above, Applicant has not met either of the two elements of the written description requirement as set forth in the court's decision in Eli Lilly. As a result, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
Response to Arguments
Applicants’ arguments filed 06/18/2026 have been fully considered but they are not persuasive.
Applicant argues specification provides express written description support for each of SEQ ID NOs: 10-41, including their complete amino acid sequences in the sequence listing, their structural characterization as engineered variants comprising domain I (SEQ ID NO: 139) and domain II (SEQ ID NO: 145) from the native Cry89Aa protein of SEQ ID NO: 1 with distinct heterologous domain III regions (see e.g., Examples 1-2; FIG. 2 and 5-7), and their demonstrated insecticidal activity against Lepidopteran pests (see e.g., Tables 1, 3, and 4) thus the claim recite specific sequence (Response to Rejection, page 8, first paragraph). Applicants’ arguments have been fully considered but they are not persuasive since Applicant has not described domain III region of any one of for example SEQ ID NOs: 10-15 (claims 40 and 72) and when combined with domain I and II as SEQ ID NOs: 139 and 145 respectively would cause insecticidal property to insect pests of fall armyworm (Spodoptera frugiperda), com earworm (Helicoverpa zea), or European com borer (Ostrinia nubilalis) other than SEQ ID NOs: 10-15 themselves. Therefore the part of the rejection has been maintained.
Following obviousness rejection has been modified in light of applicants’ amendment of claims 40 and 72 now reciting the domain III is, domain III of SEQ ID NO:10 and the polypeptide is active against CEW, FAW and ECB.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 40, 42-43, 45-46, 72-75 and 77-79 are rejected under 35 U.S.C. 103 as being unpatentable over Kelly et al. (US patent Application Pub. No.: US 2024/0240200 A1, Date of Patent: Jul. 18, 2024) and further in view of by Naga et al. (US Patent Application Pub. No.: US 2021/0347830 A1, Pub. Date: Nov. 11, 2021).
Claims are drawn to an engineered insecticidal polypeptide comprising a domain I and II as SEQ ID NOs: 139 and 145 respectively and a heterologous domain III from SEQ ID NO:10. Claims are further drawn to the polynucleotide encoding the protein is linked to heterologous regulatory element and plant cell or bacteria comprising the polynucleotide.
Applicant discloses an engineering method to alter SEQ ID NO: 1 by exchanging domain III (SEQ ID NO: 151) of SEQ ID NO: 1, a Cry89Aa class native polypeptide (formerly Cry1N class, as disclosed in U.S. Provisional Patent Application No. 63/665,914 and International Patent Application No. PCT/US2025/014957) (page 44, paragraphs 135-136). Therefore, SEQ ID NO: 151 is domain III region. Applicant describes SEQ ID NO: 139 is domain I region, SEQ ID NO:145 is the domain II region and SEQ ID NO:161 is the border/linker II region and SEQ ID NOs:151 is domain III region (page 44, paragraph 137).
Regarding claim 40, alignment of SEQ ID NO: 139, 145, 161 and 151 showed that domain I, domain II, border II and domain III regions of SEQ ID NO:1 had 100% identity to SEQ ID NO:12 of Kelly et al. (see alignment below). Therefore, the polypeptide of SEQ ID NO:12 comprises domain I, domain II, border II and domain III of SEQ ID NO:1.
Kelly et al. claim 1 teaches SEQ ID NO:12 has pesticidal activity.
Alignment of SEQ ID NOs: 139, 145, 161 and 151 to Kelly et al.’s SEQ ID NO:12.
Query: unnamed protein product Query ID: lcl|Query_4971823 Length: 634
>unnamed protein product
Sequence ID: Query_4971825 Length: 593
Range 1: 1 to 593
Score:1220 bits(3157), Expect:0.0,
Method:Compositional matrix adjust.,
Identities:593/633(94%), Positives:593/633(93%), Gaps:40/633(6%)
Query 2 NQNNQNVTPDNSVKYPLADDQTTPLAENNQDVTSDNKENSKVINCLSDPNSDLEKSGGGV 61
NQNNQNVTPDNSVKYPLADDQTTPLAENNQDVTSDNKENSKVINCLSDPNSDLEKSGGGV
Sbjct 1 NQNNQNVTPDNSVKYPLADDQTTPLAENNQDVTSDNKENSKVINCLSDPNSDLEKSGGGV 60
Query 62 ALDITMSLISELLGAVPVAGSYIQFVFDKLWSIFGPSDWDSLMEHVEALIDSKIQEHVKR 121
ALDITMSLISELLGAVPVAGSYIQFVFDKLWSIFGPSDWDSLMEHVEALIDSKIQEHVKR
Sbjct 61 ALDITMSLISELLGAVPVAGSYIQFVFDKLWSIFGPSDWDSLMEHVEALIDSKIQEHVKR 120
Query 122 NAQNELEAIQRNLETYLKFLYAWENDSNNLRARAVVKDQFVGLEQTLERKMVSVFGSTGH 181
NAQNELEAIQRNLETYLKFLYAWENDSNNLRARAVVKDQFVGLEQTLERKMVSVFGSTGH
Sbjct 121 NAQNELEAIQRNLETYLKFLYAWENDSNNLRARAVVKDQFVGLEQTLERKMVSVFGSTGH 180
Query 182 EVHLLPIFAQAANLHLMLLRDAEKYGNRWGWTDREIQVYYDNQVRYIHEYTDHCVKYYNQ 241
EVHLLPIFAQAANLHLMLLRDAEKYGNRWGWTDREIQVYYDNQVRYIHEYTDHCVKYYNQ
Sbjct 181 EVHLLPIFAQAANLHLMLLRDAEKYGNRWGWTDREIQVYYDNQVRYIHEYTDHCVKYYNQ 240
Query 242 GLSKLKGSTYQDWDKYNRYRREMTLTVLDLISIFPSYDTRTYPIDTIGQLTREVYSDLLI 301
GLSKLKGSTYQDWDKYN LLI
Sbjct 241 GLSKLKGSTYQDWDKYN----------------------------------------LLI 260
Query 302 ANSSGIQPFTNTDFDNILIRKPHLMDFLRHLEIFTDRHNASRHNVYWGGHRVHFSRAGDN 361
ANSSGIQPFTNTDFDNILIRKPHLMDFLRHLEIFTDRHNASRHNVYWGGHRVHFSRAGDN
Sbjct 261 ANSSGIQPFTNTDFDNILIRKPHLMDFLRHLEIFTDRHNASRHNVYWGGHRVHFSRAGDN 320
Query 362 TYHISPLYGSEANVEPTTYLSFGDSQVYRIHSKPEWDRGSTAISGSYEFRGVTGCSFYRM 421
TYHISPLYGSEANVEPTTYLSFGDSQVYRIHSKPEWDRGSTAISGSYEFRGVTGCSFYRM
Sbjct 321 TYHISPLYGSEANVEPTTYLSFGDSQVYRIHSKPEWDRGSTAISGSYEFRGVTGCSFYRM 380
Query 422 GNFPGTVALTYRQFGPELTELPWGKNGPSHRLCHVTYFRRSQAVGATSRQTLTSGLLFSW 481
GNFPGTVALTYRQFGPELTELPWGKNGPSHRLCHVTYFRRSQAVGATSRQTLTSGLLFSW
Sbjct 381 GNFPGTVALTYRQFGPELTELPWGKNGPSHRLCHVTYFRRSQAVGATSRQTLTSGLLFSW 440
Query 482 THSSAAETNNIDPEKITQIPMVKASSLGSGTSVIEGPGFTGGDILRRSSPGSTGTLRVNV 541
THSSAAETNNIDPEKITQIPMVKASSLGSGTSVIEGPGFTGGDILRRSSPGSTGTLRVNV
Sbjct 441 THSSAAETNNIDPEKITQIPMVKASSLGSGTSVIEGPGFTGGDILRRSSPGSTGTLRVNV 500
Query 542 NSPLSQRYRIRIRYASTTDLEFLVTCGGRTVNNFFPFTKTMNKGDSLTLEKFKFASFSTP 601
NSPLSQRYRIRIRYASTTDLEFLVTCGGRTVNNFFPFTKTMNKGDSLTLEKFKFASFSTP
Sbjct 501 NSPLSQRYRIRIRYASTTDLEFLVTCGGRTVNNFFPFTKTMNKGDSLTLEKFKFASFSTP 560
Query 602 FTFTQNEDTLEIFVQRFSSGEEVYIDRIEVIPV 634
FTFTQNEDTLEIFVQRFSSGEEVYIDRIEVIPV
Sbjct 561 FTFTQNEDTLEIFVQRFSSGEEVYIDRIEVIPV 593
Furthermore, Kelly et al. teaches modification in their disclosed Cry toxins can be made in their disclosed polypeptides, for example by domain III swapping resulting in hybrid toxins with improved toxicities against certain insect pests. Kelly et al. teaches domain III swapping is an effective strategy to improve toxicity of Cry toxins or to create novel hybrid toxins with toxicity against pests that show no susceptibility to the parental Cry toxins (page 8, paragraph 0046). Kelly et al. teaches position of different N-terminal, central and C-terminal domain of their pesticidal protein of SEQ ID NO:12 wherein their C-terminal portion is location at from 497-634 (see table 12). Kelly et al. furthermore teaches many of the Cry1C and Cry1A pesticidal polypeptides and their different N-terminal, central, and C-terminal domain (i.e. domain III) (page 9, Table 2).
Kelly et al. does not teach combining the domain III region of SEQ ID NO:10 that would lead to an insecticidal polypeptide active against FAW, CEW or ECB.
Furthermore, Naga et al. teaches SEQ ID NOs: 96, 97, 99 and 102 that has their domain III region which has very high similarity to the domain III of applicant’s SEQ ID NO:10 (see alignment below of SEQ ID NO:97 and applicant’s SEQ ID NO:10). Since applicant has not specifically defined the domain III region of SEQ ID NO:10, the c-terminal of the polypeptide chain which are identical to the sequence of c-terminal of the applicant’s SEQ ID NO:10 would have been the domain III region.
Naga et al. teaches shuffling construct comprising the domain III of their SEQ ID NO:97 which was generated from Cry toxin fragment shuffling which is shuffled at start of the domain III (i.e. F2) (see Figure 4) which causes insecticidal activity against CEW, FAW and ECB, SBL and VBC (see Figure 7), also showed in Table 9 that showed the absence of activity against FAW. Naga et al. teaches SEQ ID NO:97 and fragment would have insecticidal property (claim 32). Maga et al. teaches the domain 3 of SEQ ID NO:97 comprise 1Cb(F2 fragment) wherein Figure 11 showed 1Cb is SEQ ID NO:169 encoded by SEQ ID NO:147.
Naga et. al. teaches method of altering insecticidal activity of insecticidal polypeptide by shuffling domain 3 of Cry1Cb as SEQ ID NO:169 (i.e. domain III) (claims 27-30).
PNG
media_image6.png
401
953
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Greyscale
Thus it would have been obvious to a skilled in the art before the effective date of filling of the invention from teaching, suggestion, or motivation in the Kelly et al. to swap the domain III of their disclosed SEQ ID NO:12 that comprise the domain I, II and the border II of SEQ ID NO:161 of SEQ ID NO:1 with the domain III of Naga et. al.’s SEQ ID NO:97 (i.e. domain III region of applicant’s SEQ ID NO:10) that would lead to insecticidal activity against CEW, FAW or ECB upon screening of the insect damage. That would lead to the invention of the recited engineered insecticidal polypeptide.
Alignment of SEQ ID NO:10 to Issued_Patents_AA database:
RESULT 2
US-17-269-314-97
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 97, US/17269314
Patent No. 11878999
GENERAL INFORMATION
APPLICANT: Pioneer Hi-Bred International, inc.
APPLICANT: Kikani, Naga
TITLE OF INVENTION: INSECTICIDAL PROTEINS AND METHODS FOR THEIR USE
FILE REFERENCE: 6806-WO-PCT
CURRENT APPLICATION NUMBER: US/17/269,314
CURRENT FILING DATE: 2021-02-18
NUMBER OF SEQ ID NOS: 278
SEQ ID NO 97
LENGTH: 612
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
Query Match 52.3%; Score 1736.5; Length 612;
Best Local Similarity 58.7%;
Matches 360; Conservative 73; Mismatches 147; Indels 33; Gaps 13;
Qy 34 SDNKENSKVINCLSDPNSDLEKSGGGVALDITMSLISELLGAVPVAGSYIQFVFDKLWSI 93
|: : || : ||: | :|: ||:| ||::||||| :| |: :||||::|||
Db 3 SNEHDYLKVCDDLSETN--MERFDKNDALEIGMSIVSELLGMIP-GGAALQFVFNQLWSR 59
Qy 94 FGPSDWDSLMEHVEALIDSKIQEHVKRNAQNELEAIQRNLETYLKFLYAWENDSNNLRAR 153
| | | : ||||| |||:||: : | | :|| : ||||||:| | |||:: : :|:
Db 60 LGDSGWSAFMEHVEELIDTKIEGYAKNKALSELAGMHRNLETYIKLLNEWENNTGSSKAQ 119
Qy 154 AVVKDQFVGLEQTLERKMVSVFGSTGHEVHLLPIFAQAANLHLMLLRDAEKYGNRWGWTD 213
| : | ||| :|| | | |: || :: |||||||:|||| || ||||:|
Db 120 GRVANYFESLEQAVERGMPQ-FAVGNFEIPLLTVYVQAANLHLLLLRDVSVYGKRWGWSD 178
Qy 214 REIQVYYDNQVRYIHEYTDHCVKYYNQGLSKL--KGSTYQDWDKYNRYRREMTLTVLDLI 271
::|::||: ||:| ||||:|| :||:|| || |||:|||| |||:|||:||||||::
Db 179 QKIKIYYEKQVKYTHEYTNHCSTWYNRGLDKLKNKGSSYQDWYNYNRFRREITLTVLDIV 238
Qy 272 SIFPSYDTRTYPIDTIGQLTREVYSDLLIANSSGIQPFTNTDFDNIL----IRKPHLMDF 327
::|| || : ||| |:||||||||:| || : :| |:: || |||:||
Db 239 AVFPHYDVKAYPIQTVGQLTREVYTDPLINFNPQLQSVAQLPTFNVMESNAIRNPHLVDF 298
Qy 328 LRHLEIFTDRHNASRHNVYWGGHRVHFSRAGDNTYHISPLYGSEANVEPTTYLSFGDSQV 387
| :| |||| : || ||||||| | | |:|| || || :| : |
Db 299 LNNLRIFTDWFSVGRH-YYWGGHRVISKRVGGREITF-PIYGREAKQEPPRSFTF-NGPV 355
Qy 388 YRIHSKPEW-DRGSTAISGSYEFRGVTGCSFYRMGNFPGTVALTYRQFGP--ELTELPWG 444
:| | | | : : ||: | || | ||| || ||||| |
Db 356 FRTLSNPTLRPLQQPAPAPPFNLRGLEGVKFYTPTN-----TFTYRGRGPRDSLTELPPG 410
Qy 445 ------KNGPSHRLCHVTYFRRSQAVGATSRQTLTSGLLFSWTHSSAAETNIIYPDVINQ 498
: | |||||| |: :|| ||:|::||||| || : ||||||||||
Db 411 DTSVLPREGYSHRLCHATFIQRS------GTPFLTTGVVFSWTHRSATDRNIIYPDVINQ 464
Qy 499 IPLVKAFNLTSGTSVVRGPGFTGGDIIRTNVNGSVLSMSLNFSNTTLQRYRVRVRYAASQ 558
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 465 IPLVKAFNLTSGTSVVRGPGFTGGDIIRTNVNGSVLSMSLNFSNTTLQRYRVRVRYAASQ 524
Qy 559 TMVMSVTVGGSTTGNQGFPSTMSANGALTSQSFRFAEFPVGISASGSQGASISISNNVGR 618
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 525 TMVMSVTVGGSTTGNQGFPSTMSANGALTSQSFRFAEFPVGISASGSQGASISISNNVGR 584
Qy 619 QMFHLDRIEFLPV 631
|||||||||||||
Db 585 QMFHLDRIEFLPV 597
Regarding claim 42, Kelly et al. claim 10 teaches the polynucleotide encoding the Kelly et al.’s SEQ ID NO:12 operably linked to a heterologous promoter.
Regarding claims 43, 45-46, Kelly et al. claims 11 and 21 teaches plant and plant cell comprising the polynucleotide encoding the Kelly et al.’s SEQ ID NO:12.
Regarding claim 72-75, 77-79, Kelly et al. claims 10-14, 21 teaches a nucleic acid construct, expression construct, a vector and a plant cell comprising the construct.
Response to Arguments
Applicants’ arguments filed 06/18/2026 have been fully considered but they are not persuasive.
Applicant argues 18-20, 22-23, and 27 are canceled herein without prejudice or disclaimer therefore obviousness rejections under§ 103 are now moot.
Applicant's arguments have been fully considered but they are not persuasive since new art has been added as Naga et al. which teaches shuffling of domain III region of SEQ ID NO:40 to other insecticidal protein for example protein of Kelly et al. that would lead to diversity for selection of insecticidal activity for CEW, FAW and ECB that would lead to a skill in the art to screen for the insecticidal activity leading to development of variants of proteins as recited in claims 40 and 72, see analysis above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 40, 42-43, 45-47, 50-51, 53-54, 72-75 and 77-79 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19578376 (Hereafter cited as Application ‘376) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 40, 42-43,45-46, Application ‘376 claim 1 recite a nucleic acid molecule encoding SEQ ID NO:41 integrated into a plant cell and the nucleic acid molecule is operably linked to a heterologous promoter and that has insecticidal activity against FAW, CEW or ECB. Furthermore, alignment of SEQ ID NOs: 139 and 145 to the SEQ ID NO:41, showed the SEQ ID NO:41 comprise domain I and II as SEQ ID NOs: 139 and 145 respectively (see alignment below) that would further comprise domain III region as recited in claim.
Regarding claim 47, 50-51, 53-54, Application ‘376 claim 1 recite a polypeptide having SEQ ID NO:41 that has insecticidal activity against FAW, CEW or ECB and the polypeptide is in plant cell, and the nucleic acid molecule is operably linked to a heterologous promoter. ‘376 claim 10 recite SEQ ID NO:41 is a polypeptide.
Regarding claims 72-75 and 77-79, Applicant’s claim 72 recite the nuclei acid construct comprise the nucleic acid operatively linked to heterologous regulatory element (i.e. promoter) encoding SEQ ID NO:41, therefore Application ‘376 claim 1 recite the construct and the recombinant nucleic acid expresses the polypeptide in a plant cell. The transformation of plant would have been varied out using a vector and the development of vector is within the scope of the skilled in the art of known nucleic acid.
Alignment of SEQ ID NOs: 139 and 145 to the SEQ ID NO:41.
Query: unnamed protein product Query ID: lcl|Query_4189943 Length: 632
>unnamed protein product
Sequence ID: Query_4189945 Length: 431
Range 1: 1 to 431
Score:891 bits(2302), Expect:0.0,
Method:Compositional matrix adjust.,
Identities:431/471(92%), Positives:431/471(91%), Gaps:40/471(8%)
Query 1 NQNNQNVTPDNSVKYPLADDQTTPLAENNQDVTSDNKENSKVINCLSDPNSDLEKSGGGV 60
NQNNQNVTPDNSVKYPLADDQTTPLAENNQDVTSDNKENSKVINCLSDPNSDLEKSGGGV
Sbjct 1 NQNNQNVTPDNSVKYPLADDQTTPLAENNQDVTSDNKENSKVINCLSDPNSDLEKSGGGV 60
Query 61 ALDITMSLISELLGAVPVAGSYIQFVFDKLWSIFGPSDWDSLMEHVEALIDSKIQEHVKR 120
ALDITMSLISELLGAVPVAGSYIQFVFDKLWSIFGPSDWDSLMEHVEALIDSKIQEHVKR
Sbjct 61 ALDITMSLISELLGAVPVAGSYIQFVFDKLWSIFGPSDWDSLMEHVEALIDSKIQEHVKR 120
Query 121 NAQNELEAIQRNLETYLKFLYAWENDSNNLRARAVVKDQFVGLEQTLERKMVSVFGSTGH 180
NAQNELEAIQRNLETYLKFLYAWENDSNNLRARAVVKDQFVGLEQTLERKMVSVFGSTGH
Sbjct 121 NAQNELEAIQRNLETYLKFLYAWENDSNNLRARAVVKDQFVGLEQTLERKMVSVFGSTGH 180
Query 181 EVHLLPIFAQAANLHLMLLRDAEKYGNRWGWTDREIQVYYDNQVRYIHEYTDHCVKYYNQ 240
EVHLLPIFAQAANLHLMLLRDAEKYGNRWGWTDREIQVYYDNQVRYIHEYTDHCVKYYNQ
Sbjct 181 EVHLLPIFAQAANLHLMLLRDAEKYGNRWGWTDREIQVYYDNQVRYIHEYTDHCVKYYNQ 240
Query 241 GLSKLKGSTYQDWDKYNRYRREMTLTVLDLISIFPSYDTRTYPIDTIGQLTREVYSDLLI 300
GLSKLKGSTYQDWDKYN LLI
Sbjct 241 GLSKLKGSTYQDWDKYN----------------------------------------LLI 260
Query 301 ANSSGIQPFTNTDFDNILIRKPHLMDFLRHLEIFTDRHNASRHNVYWGGHRVHFSRAGDN 360
ANSSGIQPFTNTDFDNILIRKPHLMDFLRHLEIFTDRHNASRHNVYWGGHRVHFSRAGDN
Sbjct 261 ANSSGIQPFTNTDFDNILIRKPHLMDFLRHLEIFTDRHNASRHNVYWGGHRVHFSRAGDN 320
Query 361 TYHISPLYGSEANVEPTTYLSFGDSQVYRIHSKPEWDRGSTAISGSYEFRGVTGCSFYRM 420
TYHISPLYGSEANVEPTTYLSFGDSQVYRIHSKPEWDRGSTAISGSYEFRGVTGCSFYRM
Sbjct 321 TYHISPLYGSEANVEPTTYLSFGDSQVYRIHSKPEWDRGSTAISGSYEFRGVTGCSFYRM 380
Query 421 GNFPGTVALTYRQFGPELTELPWGKNGPSHRLCHVTYFRRSQAVGATSRQT 471
GNFPGTVALTYRQFGPELTELPWGKNGPSHRLCHVTYFRRSQAVGATSRQT
Sbjct 381 GNFPGTVALTYRQFGPELTELPWGKNGPSHRLCHVTYFRRSQAVGATSRQT 431
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Summary
No claim is allowed.
Claims 47, 50-51 and 53-54 are free of prior art. The close prior art is Kelly et al. which teaches SEQ ID NO:12 wherein alignment of SEQ ID NO: 139 (domain I) , 145 (domain II), and 161 (border II) showed that the regions have 100% identity to SEQ ID NO:12 of Kelly et al. (see alignment above). Therefore, the polypeptide of SEQ ID NO:12 comprises domain I, domain II, border II. The inventive distinction is the specific polypeptide having an amino acid sequence of any one of SEQ ID NOs: 10-41, 43-45, 235-255, or 258-273 (claim 47). Kelly et al. does not teach to develop the specific sequences of SEQ ID NOs: 10-41, 43-45, 235-255, or 258-273 that would have insecticidal activity against one or more Lepidopteran insect pests selected from fall armyworm (Spodoptera frugiperda), corn earworm (Helicoverpa zea), or European corn borer (Ostrinia nubilalis).
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/SANTOSH SHARMA/Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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